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IChaseFrisbees
Regular Member


Date Joined Nov 2009
Total Posts : 32
   Posted 11/13/2009 2:23 AM (GMT -7)   
Hi folks, I'm new here but I've had IBS for around 14 months or so now. Brief history, stool test for parasites came back negative, colonoscopy and endoscopy were both clean, negative for celiac, never had any inflammation, pancreas etc. all check out as okay, ultrasound clean, gosh that's about all I can think of right now (SO MANY TESTS!)

I did have a stool test for bacteria come back showing I was depleted in all the good beneficial bowel flora, but probiotics have thus far been useless. I recently heard that parasite tests are notoriously inaccurate, and that just because it comes back negative doesn't mean you don't have an infestation. I don't know whether this is true or not, but I also haven't heard anything that would imply that treating for parasites anyway has any risk!

I've thought a lot about colon cleansing, but in the end I don't really buy all of that "built up waste" stuff (just my opinion), but I do feel that parasites are a real possibility. Does anyone know about a broad spectrum way to treat for parasites (preferably no drugs)? Since I don't have a specific worm or anything like that I'm wondering if there is just a general, quality parasite purger that can let me rest easily knowing that another possibility has been scratched off the list.

Thanks so much, at this point I'm very much leaning towards alternative treatments and medicine, as my GI guy prescribed me a low-dose antidepressant and told me to "go back to eating cakes and cookies and everything else" when various diets failed to yield any improvement (gluten free then later GAPS.)

Any insight is appreciated, thanks again.

-Jesse

shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/13/2009 10:27 AM (GMT -7)   
Jesse one thing you could try is gut directed hypnotherapy as a safe and very possible effective method if you want to go a more natural root. It works for the majority of people who try it and has long lasting symptom relief. IF you have questions about why let me know. Its works on the the way the brain and gut communicate.

Also read this article. Stool testing is pretty accurate along with blood testing for parasites. However, certain symptoms would not be found with parasites that are found in IBS and vise versa.

Johns Hopkins gastroenterology and hepatology

"Stool testing for Ova and Parasites are generally of low yield (0-2%) and the outcome of therapy on symptoms of IBS in patients with parasites is unknown. "

http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_id=551CDCA7-A3C1-49E5-B6A0-C19DE1F94871&GDL_Disease_id=F5E21D6B-A88E-44F9-900F-7E295C50D38B

You might want to read the whole site.

http://www.hopkins-gi.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_id=024CC2E1-2AEB-4D50-9E02-C79825C9F9BF&GDL_Disease_id=F5E21D6B-A88E-44F9-900F-7E295C50D38B

Who did the stool testing for bacteria?
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


IChaseFrisbees
Regular Member


Date Joined Nov 2009
Total Posts : 32
   Posted 11/13/2009 11:26 AM (GMT -7)   
Hi there, I don't remember the exact lab (all my medical files are at my parent's house) but I'll find out and get back here! I've tried hypnotherapy, where I had an appointment, then the doc made a cd that I'm supposed to listen to...to be honest with you hypnotherapy feels like symptom control, and I guess I'm still in this place where I'm looking to get cured; I've only had this for like 14 months or so, and I like to think of it more as "Leaky Gut" or something along those lines than the IBS that the doctors have been talking about.

I asked this question on another forum; when do you give up finding a cure and recognize that you have a nervous disorder of the bowel or whatever?

Thanks for your reply though,

-Jesse

shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/13/2009 3:12 PM (GMT -7)   
There is a specific symptoms for an IBS diagnoses minus red flags. But no actual test or biological marker.

The HT might help IBS way more then you might think and if you have IBS its all about symptom control. In fact the HT might be better at the problem of IBS on the physiological side then the majority of most IBS treatments if it works for you. It is one of the most successful treatments for IBS to date.

I will come back to that later.

IBS is not "leaky gut" and the medical profession does not recgonize leaky gut. They do recgonize gut permeablity, but that is somewhat different then the alternative term "leaky gut."

They have already found some mechanisms that generate the symptoms of IBS they already know about, although not the exact cause/causes.

First

http://aboutibs.org/site/about-ibs/symptoms/diagnosis

You might want to read this also, scroll down the page to it.

Diagnostic Testing in Irritable Bowel Syndrome: Theory vs. Reality

http://www.med.unc.edu/medicine/fgidc/Autumn_2009_Digest.pdf

Do you have rectal hypersensivity by any chance?

Do you have pain or discomfort?

Do you have the sensation of incomplete evacuation?

Altered bowel movements?

Relief after a bowel movement?
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


IChaseFrisbees
Regular Member


Date Joined Nov 2009
Total Posts : 32
   Posted 11/13/2009 5:10 PM (GMT -7)   
Hi there, the way I understand it IBS just means you have a set of symptoms (in my case loose stools, gas, bloating, incomplete evacuation, abnormal stools, occasional cramping) and they can't figure out what's causing it, right? A doctor I saw called it a "throw away diagnosis" or a diagnosis by elimination: you don't have UC or Crohn's or parasites or giardia or anything else, so you must just have IBS.

I know that the docs don't believe in "leaky gut" or any of that stuff, but I'm just not sure that I'm ready to agree that my IBS doesn't have a cure or underlying cause. I had SIBO, but 2 courses of antibiotics didn't lead to any improvements. A stool test for bacterial levels (which the docs don't recognize either) came back showing that I had 0 on a scale of 1-4 of the beneficial flora, making me think that has something to do with it. But my GI guy didn't even consider that; he just gave me a tricyclic dealy and told me to eat fiber.

No saying I'm against doctors, they've been extremely helpful to me thus far, but I do believe in alternative treatments/theories that my docs have dismissed.

Little to no pain, some discomfort which is generally relieved after a BM, but I always have incomplete evacuation, so never fully relieved. What's rectal hypersensitivity? I'm not sure I know what the regular sensitivity would be haha.

Thanks,

-Jesse

shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/13/2009 6:25 PM (GMT -7)   
"the way I understand it IBS just means you have a set of symptoms"
 
Nope they are a specific cluster of symptoms, minus red flags. Not just GI symptoms.
 
The diagnoses is no longer a diagnoses of exclusion or a "throw away diagnoses" That is wrong.
 
"I know that the docs don't believe in "leaky gut" or any of that stuff,"
 
No and there is a reason for that, but there is intestinal permeablity. That is one way you absorb nutrients. The functioning of sigmoid colon is mainly IBS.
 
Your IBS has an underlying cause, they just don't know exactly what it is yet, but a ton of good research has been done in the last five years. They know quite a bit about the d and c and d/c and pain aspects. In fact many issues about IBS.
 
Depending on the test you might not have had SIBO?
 
also you can have sibo and IBS, you can also have sibo without IBS and you can have just IBS.
 
The tricyclic is to help pain and gut functioning and increased anxiety.
 
This and some of your other symptoms are hallmark IBS symptoms. "generally relieved after a BM" and incomplete evacuation. In IBS the colon doesn't function normally and those are some of the abnormal symptoms in the cluster.
 
I can't diagnose you though, but your symptoms are consistent with IBS.
 
I am not sure you know the actual theories already on IBS, especially over the last five years and that is important in understanding IBS, which is a majorally complex condition.
 
There are just someways the body works that are important in IBS for one.
 
The majority of the bodies serotonin a neurotransmitter is located in the gut in specific cells that release it to start disgestion. This seems to be out of whack in IBS, but that is not the only issues.
 
 Video Corner: Serotonin
 
Increasingly our understanding of IBS is that it is a heterogeneous disorder – that is, multiple factors contribute to the well defined symptoms of the disorder. One of these suspected underlying dysfunctions involves serotonin, which is a neurotransmitter or messenger to nerves. Most serotonin in the body is in cells that line the gut where it senses what is going on and through receptors signals nerves that stimulate a response. The serotonin must then be reabsorbed (a process called re-uptake) into cells. This process appears to be disrupted in people with IBS.
 
 
This is from the chairman of the Rome committe to diagnose these disorders, who I wrote to and know personally. 
 
Since I have suffered for thirty nine years of IBS I wonder what role foods play in IBS. So I asked Dr Douglas Drossman at  the UNC Center for Functional GI and Motility disorders and here was his response. This is not a substitute for seeking medical advise from your doctor on any specific conditions you may have, but for educational purposes only.
 Dr. Drossman is a Co-director of the Center and Professor of Medicine and Psychiatry at UNC-CH. He established a program of research in functional gastrointestinal disorders at UNC more than 15 years ago and has published more than 250 books, articles, and abstracts relating to epidemiology, psychosocial and quality of life assessment, design of treatment trials, and outcomes research in gastrointestinal disorders.
 
Dr Drossman's comments on foods for IBS Health.
Shawn,
To say that people with IBS may get symptoms from food intolerances is an acceptable possibility, since the gut will over react to stressors of all types including food (high fat or large volumes of food in particular). Furthermore, there can be specific intolerances. So if you have a lactose intolerance for example, it can exacerbate, or even mimic IBS. Other examples of food substances causing diarrhea would be high consumers of caffeine or alcohol which can stimulate intestinal secretion or with the latter, pull water into the bowel (osmotic diarrhea). The same would be true for overdoing certain poorly absorbed sugars that can cause an osmotic type of diarrhea Sorbitol, found in sugarless gum and sugar substituted foods can also produce such an osmotic diarrhea. Even more naturally, people who consume a large amount of fruits, juices or other processed foods enriched with fructose, can get diarrhea because it is not as easily absorbed by the bowel and goes to the colon where it pulls in water. So if you have IBS, all of these food items would make it worse.
 
However, it is important to separate factors that worsen IBS (e.g., foods as above, stress, hormonal changes, etc.) from the cause or pathophysiology of IBS. Just like stress doesn't cause IBS, (though it can make it worse), foods must be understood as aggravating rather than etiological in nature.
 
The cause of IBS is yet to be determined.  However, modern research understands IBS as a disorder of increased reactivity of the bowel, visceral hypersensitivity and dysfunction of the brain-gut axis. There are subgroups being defined as well, including post-infectious IBS which can lead to IBS symptoms. Other work using brain imaging shows that the pain regulation center of the brain (cingulate cortex) can be impaired, as well as good evidence for there being abnormalities in motility which can at least in part explain the diarrhea and constipation. So finding a specific "cause" of IBS has grown out of general interest in place of understanding physiological subgroups that may become amenable to more specific treatments.  Hope that helps.
Doug
 
 
Rectal hypersensivity is a sensitive rectum, a lot of IBSers have it but not all. It can also be part of the sensation of incomplete evacuation. There is nothing in there or a very small amount, but the rectum still sends the signals to evacuate.
 
Since you have only had this for 14 months what do you think it started from, did you have any gut problems or anything, before hand?
 
IBS is a distint clinical entity.
 
 
 
 
 
 
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/13/2009 6:29 PM (GMT -7)   
PS this are basically not symptoms "generally relieved after a BM" and incomplete evacuation." of a parasite.
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


IChaseFrisbees
Regular Member


Date Joined Nov 2009
Total Posts : 32
   Posted 11/14/2009 12:09 AM (GMT -7)   
Hi there, I think we may be mis-communicating a bit; I have IBS. I got the diagnosis, the doc said that's what it was, so that's sorted out. My search is for what causes my IBS, because I didn't have IBS my whole life, so I'm hopeful that I won't have it for the rest of my life as well, you know? It all started one night when I went to a party, got way too drunk, did some weed cupcakes, then the next day I had D, the day after that I passed a white stool and from then on I've settled into more or less the symptoms I described in my last post.

There are so many things out there people say will get rid of your IBS (food allergy avoidance, GAPS diet etc.) many of which seem more plausible than others. I'm just not quite ready to concentrate on symptom relief rather than keep looking for causes to treat. I did have an IGA test where I reacted to gluten, but I didn't have any problems with wheat for the first 17 years of my life, so something must have changed to make me react to that, right? Intestinal permeability seems like a logical possibility.

Thanks a lot for your input,

-Jesse

shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/14/2009 10:55 AM (GMT -7)   
Then you should accept the IBS diagnoses and work on things that will help IBS.

You may or maynot have IBS the rest of your life, its a chronic condition. Although in a small amount of people it can go away.

Experts don't use the word "cure." As the exact cause has not been established yet. You can't totally "cure" something you don't know the exact cause or cause of, no more then you could "cure" everyones migranes for example.

"There are so many things out there people say will get rid of your IBS (food allergy avoidance, GAPS diet etc.) many of which seem more plausible than others."

IBS is NOT a food allergy, so diet helps because the bowel is reactive to many things as noted above, stress, hormones, foods for a variety of reasons ect.. There are basic foods to try to eliminate at first just to see if it helps. For example soda, which has nothing to do with a food allergy or intolerence. Food allergies and food intolerences are not the same thing either.

There are specific foods to avoid and see if it helps.

Food alergies can just start up in some people when they didn't have one before, but you have IBS as well and a person can have both problems. You should actually be tested for celiac then, but it also looks like you have some other symptoms that are specific to IBS.

There are thousands of people and Doctors looking at the "cause/causes' of IBS and 19 million pubmed abstracts, in all fields of medicine. They have not found the exact cause/causes yet, but they do understand it better then they did even five years ago. Education on IBS is a key to treating it the most effectively.

So they are way ahead in research and understanding IBS then you may think or know on understanding IBS as are millions of IBSers who have had this a long time and have gone through what you are right now. Symptoms management can make the symptoms better and may even make some go away, even without knowing the exact cause and that is a gola to feel better, until they make even more progress in figuring it out.

"Intestinal permeability" is not really a condition on its own, it is a result of other conditions and a normal way the gut functions to absorb nutrients into the blood stream.

Certain probiotics have shown some evidence of healing damaged cells in the gut. Stress also increases intestinal permeability.

You may also want to read this for general information.

http://www.allergy.org.au/pospapers/unorthodox.htm

For the most part symptoms relief is treating some of the underlying causes and specifically triggers to underlying cause/causes and also placebo effects can happen often in IBS, other wise you wouldn't get symptoms relief. However, somethings that may give relief for IBS, maybe misinterpreted in why they give relief by a person.

There are many papers on, very in depth complex reasons for IBS symptoms if you want to learn them.

http://www.ibs.med.ucla.edu/PDFs/IBSReviewArticle.pdf
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


IChaseFrisbees
Regular Member


Date Joined Nov 2009
Total Posts : 32
   Posted 11/15/2009 1:53 AM (GMT -7)   
Hmm, I guess I'm a little confused. I'm not quite sure why you keep saying IBS is separate from other things, say food sensitivities, allergies or intolerances (all different things, but what I mean is for my example we can just pick one). I mean, IBS can start at any time, and then you said food allergies can start at any time as well. So what if you have food allergies, and you and your doctor don't know, so your doctor diagnoses you of having IBS, but then you find out about your food problems, remove the foods from your diet and get better? Or the same case, except replace food allergies with SIBO; you get diagnosed with IBS, but upon discovery and treatment of your SIBO all symptoms go away?

I guess I'm getting lost in the cause of IBS. You say they don't know the cause, but then also you're very sure that IBS is a separate condition of it's own quite apart from any food allergies or excessive permeability factors or SIBO. So in cases like the above mentioned, couldn't you argue that SIBO is masquerading as IBS? So at this point you have a diagnosis of IBS, but you also know that you've made a full recovery when treated for SIBO. And here I think is where I'm getting confused; for if SIBO and IBS are truly separate conditions than the patient in the above case never really had IBS at all, but rather had undiscovered SIBO. But then if SIBO or other factors can be in this way "mistaken" for IBS, then how can you possibly ever tell that you have this unique condition called "IBS" and not some other problem masquerading in a similar manner? And cases like the above example are what I consider to be "causes" of IBS; that is to say the underlying condition being diagnosed in a somewhat blanket fashion.

Hopefully you can see my dilemma, if my reasoning is unclear or if I've made an error I'd be glad to clarify. I'm really hoping you can see where I'm getting confused and put me on the right track!

Thanks again for your replies,

-Jesse

shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/15/2009 12:22 PM (GMT -7)   
It is known that about 30% and maybe even more people develop what is called Post infectious IBS after a bout of enteric-Gastroenteritis from a virus or bacterial pathogens.
 
Not all people who get enteric-Gastroenteritis develop IBS. There are certain reasons why some people develop IBS and others do not. They have studied these PI IBSers and have found problems with cells in the gut called enterochromaffin cells, mast cells. These cells especially the enterochromaffin cells have a major role to play in gut functioning and sending signals to the brain for pain and distress. There is a lot of research this is part of the problem in IBS, via serotonin.
 
They are also looking at finding a gene that may make some people more likely to develop IBS, but that has not been found yet.
 
Did you know you have a type of "brain in the gut"? Called the enteric nervous sytem. This is very important to understanding IBS.
 
But to your questions. First not all people with food allergies or sibo have IBS.
 
Second the symptoms from IBS discrimante it from food allergies or SIBO.
 
The term IBS is not interchanable with food allergies and sibo, they are all seperate conditions. A person can have more then one condition however and that makes diagnosing mulitple conditions more challenging to the doctor.
 
There are a specifc "CLUSTER" of symptoms that are used to diagnoses IBS. While some conditions may mimick some of the symptoms of IBS and vise versa, IBS has specific symptoms that discriminate it from other conditions. Such as relief after a bowel movement. That is not seen in food allergies or SIBO.
 
Recent research has shown that less IBSers had SIBO then orginally proposed and some IBSers might have sibo and IBS. A big problem here, was the test used to diagnose SIBO in IBSers was not very accurate, called the lactulose breath test. It gave bad results. Hydrogen breath testing is more accurate. Then there was media hype sibo "is the cause of IBS" when it fact that did not pan out. It did shed some light on SIBO, which the gi researchers already know about. People can have sibo and NOT have IBS and vise versa.
 
SIBO is also not its own problem, but caused by other factors that lead to sibo.
 
So its not just pick one and subsitute different conditons for each other, they are all different conditions. IBS is a functional disorder the colon is not functioning right. This is where IBS becomes extremely complex, because so many things can contribute or go wrong. Neurotransmitters for example, which signal never fibers to make things work right. Such as the serotonin problems that they have been working on for years now. It is the chemical for one that signals pain to the brain, but it is also the one that starts gut contractions. The majority is stored in the gut in those enterochromaffin cells and a lot of evidence for that process being messed up which helps explain why there is D, C and d/c in IBS. The mast cells are also very importnat, but I will get to that later. They are involved in many physiological body functioning, but are important in food allergies, but also the bodies stress responce.
 
 
I will start posting something to help explain it all.
 

Symptoms discriminate irritable bowel syndrome from organic gastrointestinal diseases and food allergy.

http://www.ncbi.nlm.nih.gov/pubmed/11007133?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=1

Small Intestinal Bacterial Overgrowth in Irritable Bowel Syndrome: Systematic Review and Meta-Analysis.
 
 
My comment from above, you'll notice only 4% had sibo.
 

The lactulose breath test for diagnosing SIBO in IBS patients: another nail in the coffin.

 

Small intestinal bacterial overgrowth in irritable bowel syndrome: association with colon motility, bowel symptoms, and psychological distress.

http://www.ncbi.nlm.nih.gov/pubmed/18482250?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=11

"SIBO is unlikely to contribute significantly to the pathogenesis of IBS."
 
There is a lot more to it all and I will post something else next on it.
 
Modern research understand IBS as a brain gut axis disorder and has for at least five years now. Both the brain and the gut "brain" bidirectional communications are strongly implicated and are both OPERATIONAL to cause the symptoms. There are reasons for these connections that have already been found and been researched in depth to try to figure out the more exact mechanisms and reasons.
 
 
 
 
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/15/2009 12:23 PM (GMT -7)   
sorry about the bold type.

What Patients Know about Irritable Bowel Syndrome (IBS) and What They Would Like to Know
National Survey on Patient Educational Needs in IBS and Development and Validation of the Patient Educational
Posted 09/18/2007

Albena Halpert, M.D.; Christine B. Dalton, PA-C; Olafur Palsson, Psy.D.; Carolyn Morris, Ph.D.; Yuming Hu, Ph.D.; Shrikant Bangdiwala, Ph.D.; Jane Hankins; Nancy Norton; Douglas Drossman, M.D.

Abstract and Introduction
Abstract
Patient education improves clinical outcomes in patients with chronic illness, but little is known about the education needs of patients with IBS.
Objectives: The objective of this study was to identify: (1) patients perceptions about IBS; (2) the content areas where patients feel insufficiently informed, i.e., "knowledge gaps" about diagnosis, treatment options, etiology, triggers, prognosis, and role of stress; and (3) whether there are differences related to items 1 and 2 among clinically significant subgroups.
Methods: The IBS-Patient Education Questionnaire (IBS-PEQ) was developed using patient focus groups and cognitive item reduction of items. The IBS-PEQ was administered to a national sample of IBS patients via mail and online.
Analysis: Frequencies of item endorsements were obtained. Clinically relevant groups, (a) health care seekers or nonhealth care seekers and ((IMG:http://www.ibsgroup.org/forums/style_emoticons/default/cool.gif) users or nonusers of the Web, were identified and grouped as MD/Web, MD/non-Web, and non-MD/Web.
Results: 1,242 patients completed the survey (371 via mail and 871 online), mean age was 39.3 ± 12.5 yr, educational attainment 15 ± 2.6 yr, 85% female, IBS duration 6.9 ± 4.2 yr, 79% have seen an MD for IBS in the last 6 months, and 92.6% have used the Web for health information. The most prevalent IBS misconceptions included (% of subjects agreeing with the statement): IBS is caused by lack of digestive enzymes (52%), is a form of colitis (42.8%), will worsen with age (47.9%), and can develop into colitis (43%) or malnutrition (37.7%) or cancer (21.4%). IBS patients were interested in learning about (% of subjects choosing an item): (1) foods to avoid (63.3%), (2) causes of IBS (62%), (3) coping strategies (59.4%), (4) medications (55.2%), (5) will they have to live with IBS for life (51.6%), and (6) research studies (48.6%). Patients using the Web were better informed about IBS.
Conclusion: (1) Many patients hold misconceptions about IBS being caused by dietary habits, developing into cancer, colitis, causing malnutrition, or worsening with age; (2) patients most often seek information about dietary changes; and (3) educational needs may be different for persons using the internet for medical information.

Introduction
Because of the impact of chronic conditions on health status and health care expenditures, managing chronic illness is one of the major challenges of modern medicine. Consequently, there is growing interest in effective educational programs, to provide patients with the necessary knowledge, skills, and confidence (self-efficacy) to manage their disease-related problems.

The goal of patient education is to facilitate changes in patient behavior for the purpose of disease management or prevention. While different health education theories focus on many different aspects of this complicated process, most agree that facilitating change of behavior requires incorporating the patients' current knowledge, prior disease experiences, attitudes, goals, motivations, and cultural perceptions. The existing literature describes educational interventions based on a variety of health education models (e.g., health belief model, the theory of planned behavior, or theory of self-efficacy) in search of effective educational models for the management of diabetes, hypertension, arthritis, and cancer. However, relatively little is known about what constitutes an effective patient education model in irritable bowel syndrome (IBS) and other functional bowel disorders. The emerging research typifies IBS as a brain-gut disorder where psychosocial factors (e.g., stress, cognitions, coping, etc.) can alter the symptoms and illness experience for better or worse. Due to these and other disease specific characteristics, that are amenable to education, we believe effective educational interventions may significantly impact the management of this common disorder. Prior to designing, studying, and implementing theory based educational strategies for IBS, we need to better understand patients' disease experience, knowledge, misconceptions, motivations, and perceptions. Few studies to date have evaluated IBS "through the patients' eyes" and none have systematically examined patients' prior knowledge about IBS.

--------------------------------------------------------------

Current Knowledge and Misconceptions about IBS
The majority of participants were able to correctly identify the symptoms and triggers of IBS. Stress at work and psychological factors were identified as triggers by more than 70% of subjects. Of note is that a significant number of patients held misconceptions, including that IBS can develop into: colitis (43% agree, 29.7% not sure), malnutrition (37.7% agree, 33% not sure), a problem needing surgery (34.3% agree, 33% not sure), and cancer (21.4% agree and 36.3% not sure). In addition, a significant number of responders thought that IBS results from lack of digestive enzymes (52.1% agree and 28.2% not sure) and would worsen with age (47.9% agreed and 30.4% not sure). The majority of the participants were optimistic that new treatments will be soon available for IBS (62.6% agreed, 27.8% not sure). See Table 3 , Table 4 , Table 5 and Table 6 for correct conceptions and misconceptions (the latter shown in italics) about IBS. Regarding knowledge about lifestyle modifications as a treatment for IBS, subjects endorsed mainly eating small meals, a high fiber, low fat diet, and avoiding milk products. Nondietary lifestyle modifications such as exercise were not frequently endorsed ( Table 7 ). The majority of our subjects were familiar with first-line treatments for IBS such as antispasmodics, antidiarrheals, and fiber agents. A total of 35% endorsed antidepressants, 16% tegaserod, and 5% alosetron ( Table 8 ). When asked if psychological treatments (cognitive behavior therapy, relaxation techniques, etc.) are potential treatments for IBS, 29.1% of participants disagreed, 41.7% agreed, and 21.4% were neutral/not sure.

Educational Needs Regarding IBS
Subjects were primarily interested in learning about what foods to avoid, causes of IBS, and coping strategies. In addition, more than 50% of responders wondered if IBS will shorten their lives, how psychological factors affect IBS, and what medications they can use to prevent an IBS "attack." Of note is that close to half of the participants wanted to know about what is a normal bowel habit, whether IBS will get worse and about available IBS research. See Table 9 and Table 10 for more detailed results on patient educational needs.

IBS Educational Needs Regarding IBS in Subgroups
Patients who used the Web, regardless of clinic status, seemed better informed about IBS and held fewer misconceptions (e.g., had less need to know what IBS is, or whether it will shorten their lives), and more interested in learning about the causes of IBS, foods to avoid, and coping strategies ( Table 13 ). Finally, based on our findings we created a summary of an IBS patient profile regarding IBS knowledge and educational needs ( Table 14 ).

===================

Discussion
Educating patients about their illnesses improves adherence to treatment, quality of life, and satisfaction with care.

___________________________________

Our survey identified what IBS patients in the United States know about their condition and what their educational needs are in regard to IBS. There are several key findings, which have implications for the way in which clinicians needs to offer education.

Patients' Misconceptions about Implications of IBS: Patients hold misconceptions about IBS developing into cancer, colitis, causing malnutrition, or shortening the life expectancy. Such misconceptions can produce great concern, anxiety, and reluctances to accept reassurance, particularly if the physician is not aware of them. This only reinforces a vicious cycle of health worry and urgent requests for diagnosis, along with increased physician visits and demands for more testing.[14] Thus it is important for educational materials to explicitly identify and address these misconceptions. In addition, clinicians need to proactively inquire about the patient's beliefs and concerns (e.g., "What do you think is causing your symptoms?" and "What are your concerns about them?"). Eliciting these thoughts and feelings will have a palliative effect on health anxiety and will lead to a more therapeutic response when the reassurance occurs within the context of the patient's expressed concerns.


Patients Seek Information Primarily about Food and Diet: Our data highlight the strong attribution patients make about the role of diet in IBS. Patients most often seek information about dietary changes and the role of food in contributing to IBS (reflected in concerns about "what foods to avoid?"). Yet because of the limited evidence for dietary factors being causative in IBS, physicians often are unable or unwilling to offer specific advice on diet. Nevertheless, our data support the importance of addressing this topic, and to educate against idiosyncratic food practices that may occur. For patients who focus excessively on unnecessary food elimination in seeking relief from IBS symptoms, it may be helpful to explain gut physiology and introduce the possibility that the ingestion of food in general, rather than specific foods, may be triggering the symptoms. Importantly, overly restrictive diets need to be replaced by recommendations for a well-balanced diet.


Patients Associate IBS with Triggers and Distress: Notably 70% of the study subjects agreed that there is a connection between their symptoms and psychological distress. However, this report contrasts with our clinical experience, since patients less frequently volunteer this association in the clinical setting, possibly out of fear of stigmatization, or the perception that this is "all in my head." Thus it is important for the clinician to be open to this option but to inquire in a matter of fact manner: "Are there any other factors that can worsen your symptoms, like diet, physical activity, or stress?" In addition to obtaining potentially meaningful clinical data that will help treatment, this approach conveys a high level of acceptance of this association as a matter of course rather than it being a "psychiatric" problem. The high level of acceptance of stress as an operative factor in IBS may relate to the population that is being drawn from the community rather than referral settings. With the latter group, the high psychosocial morbidity is associated with denial of a role for stress.[15, 16]


Patients Consider IBS a Diagnosis of Exclusion: Over 50% of the patients considered IBS to be a "catch all" diagnosis and another 22% were unsure. While this could reflect the information provided by their physicians (thus highlighting the need to also educate physicians about IBS), this misconception may motivate patients to seek more and more diagnostic studies to find "the cause." The use of the Rome criteria[17] permits the patient to have a positive diagnosis. With confidence in knowing that IBS is a specific entity, such behaviors are minimized. Thus it is important for the physician to provide proper education about the level of confidence in the diagnosis.


Web Users are More Informed about IBS: We found that IBS patients who use the Web have better knowledge about IBS in general, fewer IBS misconceptions, and are more aware of psychosocial disturbances being associated with flares. They also seem more "up to date" with commonly used medications and more interested in learning coping strategies. The implication of this finding is that the nature and content of educational interventions will differ for Web and non-Web users with IBS. Prior data suggest that more than 50% of Americans use the Web and about 52% have used the Web for obtaining medical information.[18] Similarly, the majority of our participants have used the Web for obtaining medical information (92.6%), suggesting that future Web-designed educational interventions will probably be well accepted. For the clinician, it suggests that the type of education provided (e.g., Web sites vs brochures) and its content (i.e., the educational level of the information) must be individualized to the learning style of the patient.


Our study has several limitations. First, enrollment bias exists, since subjects interested in participating in the study may have had a higher level of education and greater motivation to learn than other patients, and they may also be more symptomatic at the time of enrollment, than the average IBS patient. However, the results would certainly apply to any patient seeking or willing to receive educational information. The findings for this study group are clinically relevant since they result from a symptomatic IBS population likely to utilize health care. A subgroup of non-consulters may have different educational needs. We also think it is important that future efforts be directed toward studies that may increase interest in learning. Another limitation relates to the relevance of the information collected from subjects not recruited from internal medicine or GI clinics (e.g., online subjects). Some respondents may have entered the study without having IBS merely to obtain the compensation offered. We implemented several measures to minimize this possibility. The study was advertised only on IBS-related Web sites, subjects had to meet Rome II criteria for IBS, had to be invited to participate, and those who qualified by the screening questions did not receive the main questionnaire immediately. Instead, they were e-mailed an entry password 24-72 hr later. This made multiple attempts to qualify for participation by the same individuals unlikely. Furthermore, participants had to provide a mailing address to receive the payment, which avoided the possibility for multiple entries coming from the same person. Finally, we acknowledge that the nature of this instrument, to assess individual knowledge and informational needs, is not amenable to standard methods to assess criterion or construct validity. There is no "gold standard," and relative to other patient report instruments, such as a health related quality of life instrument, one cannot do convergent or discriminate validity with known groups because there are no other psychometric measures to correlate with the instrument. Furthermore, there are no known groups to identify since all responses are specific to the individual. However, as noted in the methods, the use of three focus groups with a broad clinical representation to generate items, and then the use of cognitive debriefing with the investigators and a sample of 50 patients, permitted the selection of the most representative sample of items that were then applied in the quantitative analysis.

-----------------------------------------

Conclusion
Our study is the first to define the conceptions, misconceptions, and educational needs of a large national sample of IBS patients. We found that many patients hold misconceptions about the condition, some of which may negatively impact patients' emotional well-being and increase their health care needs. According to our data, patients are mostly interested in dietary modifications, and learning about coping strategies and what causes IBS. Patients who use the Web have fewer misconceptions about the disease and may differ in their educational needs from non-Web users. The results of the study can be used in both daily clinical practice and as a basis for developing a variety of patient-centered IBS educational interventions.

http://www.medscape.com/viewarticle/562448
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/15/2009 12:26 PM (GMT -7)   
In IBS the brain and the gut are both operational to cause the symptoms. They have known this now for many years.

FYI

"The 'brain-gut axis' helps to explain the influence that thoughts, emotions, and psychological or social stress have on the function of the gut."

http://www.merck.com/yourhealthnow/volume2-2/braingut.html

2007 IFFGD Symposium Summary Report, Very much worth reading/state of the art research

"Stress can also significantly modify the immune response to the gut flora. So these are factors that could be affecting the sensitization in IBS and the condition itself. Brain-gut – The brain plays a role as well. The brain and the gut are connected. Thinking and feeling can have affects, influencing release of proteins that interact with the nervous system (neuropeptides), which can affect motility, secretion, blood flow, and inflammation. Stress may influence inflammatory pathways causing a dysregulation that can lead to emotional conditions and more stress – a vicious cycle. It is not a question as to whether this cycle begins in the gut or in the brain. The problem is that both systems are effected concurrently thus producing a disturbance of the regulation between the brain and gut; a “vicious cycle” with no beginning or end. Understanding this will open the door to more specific treatments. We can see examples of brain-gut interactions by looking at post-infectious IBS (PI-IBS) or dyspepsia."

Mast cells

FYI

"You have two brains: one in your head and another in your gut. Dr. Jackie D. Wood is a renowned physiologist at The Ohio State University. He calls the second brain, "the-little-brain-in-the-gut." This enteric nervous system is part of the autonomic nervous system and contains over one hundred million neurons, which is as many as are in the spinal cord. This complex network of nerves lines the walls of the digestive tract form the esophagus all the way down to the colon. This little brain in the gut is connected to the big brain by the vagus nerves, bundles of nerve fibers running from the GI tract to the head. All neurotransmitters, such as serotonin that are found in the brain are also present in the gut.

Dr Wood has discovered that this little-brain-in-the-gut has programs that are designed for our protection and which are very much like computer programs. They respond to perceived threats in the same way that the limbic system or the emotional brain does. So the threat of a gastrointestinal infection can activate the program that increases gut contractions in order to get rid of the infection. The symptoms are abdominal cramping and diarrhea.

Dr. Wood has determined that a type of cell found in the body and the gut, called the mast cell, is a key to understanding the connection of the big brain in the head with the little-brain-in-the-gut. Mast cells are involved in defense of the body. In response to certain threats or triggers, such as pollen or infection, mast cells release chemicals, such as histamine, that help to fight off the invader. Histamine is one of the chemicals that causes the symptoms of an allergy or a cold. When an infection of the gut occurs, such as food poisoning or gastroenteritis, the mast cells of the gut release histamine. The little-brain-in-the-gut interprets the mast cell signal of histamine release as a threat and calls up a protective program designed to remove the threat – at the expense of symptoms: abdominal pain and diarrhea.

The brain to mast cell connection has a direct clinical relevance for irritable bowel syndrome and other functional gastrointestinal syndromes. It implies a mechanism for linking allostasis and the good stress response to irritable states (e.g., abdominal pain and diarrhea) of the gut. Mast cells can be activated to release histamine in response to perceived psychological stress, whether the stressor or trigger is consciously perceived or not. So the end result is the same as if an infection activated the program in the-little-brain-in-the-gut: abdominal pain and diarrhea."

http://www.parkviewpub.com/nuggets/n5.html

So stress, emotions and anxiety and even PERCEIVED STRESSORS both physical and mental can trigger IBS. Part of that reaction has to do with the fight or flight reponce. This happens so fast you are NOT CONCIOUsLY AWARE of it happening.

Fight or flight

http://www.thebodysoulconnection.com/Educa...nter/fight.html

This system is connected to the autonomic nervous system and the parasympatheitc and sympathetic nervous systems. That help run digestion.

The organs (the "viscera") of our body, such as the heart, stomach and intestines, are regulated by a part of the nervous system called the autonomic nervous system (ANS). The ANS is part of the peripheral nervous system and it controls many organs and muscles within the body. In most situations, we are unaware of the workings of the ANS because it functions in an involuntary, reflexive manner. For example, we do not notice when blood vessels change size or when our heart beats faster. However, some people can be trained to control some functions of the ANS such as heart rate or blood pressure.
The ANS is most important in two situations:

In emergencies that cause stress and require us to
"fight" or take "flight" (run away)
and

In nonemergencies that allow us to "rest" and "digest."

http://faculty.washington.edu/chudler/auto.html
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/15/2009 12:31 PM (GMT -7)   
You should read this, scroll down the page to

Diagnostic Testing in Irritable Bowel Syndrome: Theory vs. Reality

http://www.med.unc.edu/medicine/fgidc/Autumn_2009_Digest.pdf
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.


shawn12
Veteran Member


Date Joined Jul 2004
Total Posts : 1293
   Posted 11/15/2009 12:38 PM (GMT -7)   
while I am at it

Just some compilations on serotonin and ibs.

Basic science is starting to understand better the enteric nervous system and the bidirectional communication between the "gut brain (ENS) and the Brain and spinal cord or Central nervous sytem. CNS

While doing so they learned the majority of serotonin 95% is stored in the gut and some of its actions in the bidirectional communication between the gut brain and the brain.

"Role of Serotonin in IBS
Disruptions in integrated communications among the CNS, ANS, and ENS may contribute to the three key pathophysiological features of IBS: altered GI motility, visceral hypersensitivity, and altered intestinal secretion. Numerous neurotransmitters and neuromodulators are involved in the communication between the IPANs and the effector systems (i.e., muscles and secretory and vascular cells) and in the mediation of bidirectional brain-gut communications. Serotonin appears to be the common link in GI motility, intestinal secretion, and pain perception and is involved at multiple levels in the bidirectional interactions between the ENS and the CNS; thus, it is considered to play an important role in the pathophysiological abnormalities observed in IBS.[4,38]"

Very importantly it "Serotonin is directly involved in initiating the ENS-mediated peristaltic reflex"

"Serotonin and the Peristaltic Reflex
Serotonin is directly involved in initiating the ENS-mediated peristaltic reflex (Figure 3).[3,45] Serotonin is released from EC cells in response to distention of the intestinal lumen (triggered by chemical or mechanical stimulation). Once released, serotonin interacts with 5-HT1p-receptors on the presynaptic nerve endings of the IPANs in the submucosal plexus. This initiates a cascade of events that facilitate the coordinated movement of the bowels. The signal from the 5-HT1p-receptors is communicated to 5-HT4-receptors located on the terminals of the submucosal IPANs. The 5-HT4-receptors then modulate peristaltic neurotransmission by facilitating the release of several neurotransmitters (e.g., acetylcholine and tachykinins) from these nerve cells, which results in muscle contractions proximal to the bolus and the release of other neurotransmitters (e.g., nitric oxide and vasoactive intestinal peptide), which in turn causes muscle relaxation distal to the bolus.[3,4,46-48] The net result is forward movement of the luminal contents through the GI tract."

also

"Serotonin and Visceral Hypersensitivity
Patients with IBS may have an increased sensitivity to painful stimuli or an exaggerated response to normal stimuli, specifically in the colon and rectum,[4,49,50] but they do not demonstrate generalized hypersensitivity to painful somatic stimulation.[38] Studies have demonstrated that patients with IBS may perceive painful stimuli in the colon and rectum with a lower threshold than do individuals without this disorder. For instance, patients with IBS are more sensitive to balloon distention in the rectum (i.e., feel discomfort at lower levels of balloon inflation) than patients without IBS.[49,50] This concept, referred to as visceral hypersensitivity, may help explain the presence of abdominal pain or discomfort in patients with IBS.

Other studies have demonstrated altered processing of brain signals. Patients with IBS may differ from patients without IBS in how their CNS integrates and processes signals from the gut.[4,50] For example, positron emission tomography, which can identify areas of increased brain blood flow in healthy controls, showed that colorectal distention activated the anterior cingulate cortex, an area rich in opiate receptors that may be involved in inhibiting painful sensations. However, this area was not activated in patients with IBS. Patients with IBS may process CNS information differently, and this processing may fail to activate brain areas involved in pain inhibition or the processing of painful stimuli.[38,51] In another study, functional magnetic resonance imaging showed that the anterior cingulate cortex was activated upon painful visceral stimulation both in patients with IBS and in controls, but that IBS patients had enhanced pain sensitivity and perception of visceral afferent (sensory) signals in the brain-gut axis corresponding to increased subjective reports of pain.[52]

Serotonin may play a major role in the visceral hypersensitivity seen in patients with IBS.[50] 5-HT3-receptors transmit sensory information from the gut to the spinal cord. Although the exact mechanism by which 5-HT4-receptors are involved in visceral sensation remains unknown, stimulation of 5-HT4-receptors has been shown to decrease the activity of the visceral afferent nerve fibers.[4,50,53,54] Peripheral 5-HT4-receptor-mediated mechanisms are thought to be involved in colonic hypersensitivity. Agonism of 5-HT4-receptors was shown to normalize pain sensitivity in an in vitro splanchnic nerve colon preparation from rats"

http://www.medscape.com/viewarticle/503569_5

This puts it a little more simply

Harvard

"The Trusted Source
.
.
Harold J. DeMonaco, M.S.

Harold J. DeMonaco, M.S., is senior analyst, Innovative Diagnostics and Therapeutics, and the chair of the Human Research Committee at the Massachusetts General Hospital. He is author of over 20 publications in the pharmacy and medical literature and routinely reviews manuscript submissions for eight medical journals.
.
.
June 19, 2001
.
A:

Irritable bowel syndrome is now recognized as a disorder of serotonin activity. Serotonin is a neurotransmitter in the brain that regulates sleep, mood (depression, anxiety), aggression, appetite, temperature, sexual behavior and pain sensation. Serotonin also acts as a neurotransmitter in the gastrointestinal tract.

Excessive serotonin activity in the gastrointestinal system (enteric nervous system) is thought to cause the diarrhea of irritable-bowel syndrome. The enteric nervous system detects bowel distension (expansion) on the basis of pressure-sensitive cells in the bowel lumen (opening). Once activated, these pressure-sensitive cells promote the release of serotonin, which in turn promotes both secretory function and peristaltic function (the contractions of the intestines that force the contents outward). At least four serotonergic receptors have been identified to be participants in the secretory and peristaltic response.

Patients with diarrhea-predominant IBS may have higher levels of serotonin after eating than do people without the disorder. This recognition led to the development of the first drug used specifically to treat diarrheal symptoms of IBS, alosetron (also known as Lotronex). Alosetron blocked the specific serotonin receptors responsible for recognizing bowel distention. In doing so, it blocked the effects of serotonin and reduced both bowel secretions and peristalsis. Constipation was the most common side effect seen. (Note: Alosetron was removed from the market by the manufacturer after repeated reports of a dangerous condition known as ischemic colitis became known.) Tegaserod (Zelmac) is another drug under development and under review by the U.S. Food and Drug Administration for approval. Tegaserod is indicated for the treatment of constipation-predominant IBS and works to increase enteric nervous system serotonin activity.

So, increasing serotonin activity in the enteric nervous system produces increased bowel secretions and peristalsis (and potentially diarrhea), whereas depressing serotonin activity produces reduced secretions and reduce peristalsis (and potentially constipation). Increasing serotonin activity in the brain would increase awareness and, in higher doses, produce anxiety, insomnia and restlessness."

However, the mechanisms are not fully understood because its so complex and other factors are also very important in IBS.

But this has in part explain why there is abnormal motility in IBS the D and c and d/c, that there is a problem in serotnin singaling in the gi tract. The cells that store the majority of it in the gi tract, EC cells or enterochromaffin cells.

In post infectious IBS, that is one of the abnormalities they found, an increase in enterochromaffin cells for one.

Distinctive Features of Postinfective Irritable Bowel Syndrome

"July 25, 2003 — Patients with postinfective irritable bowel syndrome (PI-IBS) have more diarrheal symptoms, fewer psychiatric symptoms, and a greater increase in serotonin-containing enterochromaffin (EC) cells than those whose IBS did not start after an infectious disease, according to the results of a study published in the July issue of the American Journal of Gastroenterology. The investigators speculate that subclassifying patients may allow for better and more specific therapies for some patients with IBS.

"IBS patients are heterogeneous, both in symptoms and in etiology, and progress in understanding pathogenesis has been limited for lack of objective measures to allow meaningful subdivision," write Simon P. Dunlop, MSc, from University Hospital in Nottingham, U.K., and colleagues. "Recently there has been progress in defining one subgroup of patients, i.e., those developing IBS symptoms after an episode of infective gastroenteritis."

They have also given rats a kind of IBS by messing with the EC cells.

Serotonin is also cruical for signaling sensations and pain to the brain.

However

"Visceral Sensations and Brain-Gut Mechanisms
By: Emeran A. Mayer, M.D., Professor of Medicine, Physiology and Psychiatry; Director, Center for Neurovisceral Sciences & Women's Health, David Geffen School of Medicine at UCLA

"Our brain-gut axis is not designed to generate conscious perceptions of every alteration in gut homeostasis and internal environment, in particular when these changes are chronic, and when there is no adaptive behavioral response an affected organism could generate.

Evolution has not designed our brain-gut axis to experience abdominal pain every time the number of mast cells in our ileum goes up, or the number of our serotonin containing cells goes down. It would be counter productive for an animal with a chronic parasite infestation to experience constant visceral pain, and it wouldn't have any advantage for people living in third world countries with frequent enteric infections to suffer from chronic abdominal pain. It has even been suggested that visceral pain may be a secondary phenomenon of an elaborate system of signaling non-painful signals to the brain: hunger, fullness (satiety), well-being after a meal, urge to evacuate, etc. At the same time, powerful mechanisms have evolved that keep many other aversive signals out of conscious perception: contractions, luminal distension, gas volume, low-grade inflammation, etc.

The most common symptoms of IBS patients are related to altered perception of sensations arising from the GI tract, and frequently from sites outside the GI tract, such as the genitourinary system or the musculoskeletal system. Sensations of bloating, fullness, gas, incomplete rectal evacuation and crampy abdominal pain are the most common symptoms patients experience. Numerous reports have demonstrated that a significant percentage of FBD patients (about 60%) rate experimental distensions of the colon as uncomfortable at lower distension volumes or pressures when compared to healthy control subjects. This finding of an increased perception of visceral signals ("visceral hypersensitivity") has been demonstrated during balloon distension tests of the respective part of the GI tract regardless of where their primary symptoms are – the esophagus, the stomach, or the lower abdomen.


In contrast to the current emphasis on mechanisms that may result in sensitization of visceral afferent pathways in the gut, it may well be that alterations in the way the nervous system normally suppresses the perception of the great majority of sensory activity arising from our viscera are essential for the typical symptom constellation of IBS and other functional GI disorders to develop."

http://www.aboutibs.org/Publications/VisceralSensations.html

What's New in the Management of IBS and Chronic Constipation? CME
Disclosures

Brian E. Lacy, MD, PhD


Introduction
Over 10,000 physicians, scientists, researchers, and allied health personnel from around the world attended this year's Digestive Disease Week (DDW) meeting. Judging from the large number of oral presentations and posters, research on the etiology, pathophysiology, and treatment of functional bowel disorders continues at a rapid pace. This report reviews information presented during DDW 2006 with a focus on the clinically important lower gastrointestinal functional disorders of chronic constipation and irritable bowel syndrome (IBS).

"Factors in Etiology
Although the precise etiology of IBS remains unknown, proposed mechanisms include genetic predisposition, inflammation, infection, stress, and psychological distress.[20] In addition, evidence now suggests that a deficiency in serotonin is associated with IBS with constipation, whereas excess serotonin is associated with IBS with diarrhea.

http://www.medscape.com/viewarticle/536306

MedGenMed Gastroenterology
IBS -- Review and What's New

Introduction
IBS -- a complex, multifaceted condition broadly characterized by abdominal pain/discomfort associated with altered bowel habits -- is among the most prevalent gastrointestinal (GI) motility disorders. Prevalence estimates for IBS range from 3% to 20%, with most estimates in North America ranging from 10% to 15%.[1-3] Women are affected by IBS more often than men (2:1 in the community setting and 3:1 to 4:1 in the tertiary care setting). IBS-related symptoms are often chronic and bothersome, negatively affecting patient activities of daily living (eg, sleep, leisure time), social relationships, and productivity at work or school.[4-6] Patients with IBS typically score lower than population norms or those with other chronic GI and non-GI disorders on measures of quality of life.[7-10] IBS also puts a heavy economic burden on patients, employers, and the healthcare system, resulting in more than $10 billion in direct costs (eg, from office visits, medications) and $20 billion in indirect costs (eg, through work absenteeism and reduced productivity) each year.[11-14]

Advances in research during the past several decades have provided insight into the underlying pathophysiology of IBS, particularly the role of serotonin in the GI tract; the development of stepwise, symptom-based diagnostic strategies; and the development of targeted treatment options. This review discusses recent advances in research and explores how these findings can be applied in the clinical practice setting.

"The Science of IBS
Given the lack of definitive organic markers for IBS, the absence of a unifying hypothesis regarding its underlying pathophysiology is not surprising. Nevertheless, important advances in research made during the past 50 years have brought us closer than ever to understanding the numerous putative etiologic factors involved in this multifaceted disorder, including environmental factors, genetic links, previous infection, food intolerance, and abnormal serotonergic signaling in the GI tract.

Environmental Influences
Although a patient's psychological state may influence the way in which he or she presents, copes with illness, and responds to treatment, no evidence supports the theory that psychological disturbances are the cause of IBS.[39,40] The biopsychosocial model proposed by Engel takes into account the interplay between biologic, psychological, and social factors.[41] This model proposes that there is an underlying biologic predisposition for IBS that may be acted on by environmental factors and psychological stressors, which contribute to disease development, the patient's perception of illness, and impact on treatment outcomes.[42,43]

Studies evaluating the role of acute stress have shown that stress can result in release of stress-related hormones that affect colonic sensorimotor function (eg, corticotropin-releasing factor [CRF] and inflammatory mediators [eg, interleukin (IL)-1]), leading to inflammation and altering GI motility and sensation.[44] For example, CRF-1 receptors located in the central nervous system (CNS) and gut can affect colonic motility, epithelial water transport, and gut permeability.[45] Sagami and colleagues[46] determined that the peripheral administration of a nonselective corticotropin-releasing hormone (CRH) receptor antagonist improved GI motility, visceral perception, and negative mood in response to gut stimulation in patients with IBS. These findings suggest that CRH may play an important role in the pathophysiology of IBS.

Genetics
Studies with twins have shown that IBS is twice as prevalent in monozygotic twins as in dizygotic twins.[47-49] Limited research on familial aggregation has found that individuals who have a family member (other than a spouse) with a history of abdominal pain or bowel disorder have more than 2-fold increased odds of having IBS. It is likely that environmental influences may help explain this finding (eg, awareness of the symptom status of family members may make sufferers more open to discussing their symptoms and seeking help for the condition).[50] Preliminary findings also suggest that IBS may be associated with select gene polymorphisms, including those in IL-10, G-protein GNb3, alpha adrenoceptor, and serotonin reuptake transporter (SERT).[47, 51-54] Despite these potential links, however, conclusive evidence for a genetic basis for IBS has not been established.

Postinfectious IBS
The presence of postinfectious (PI)-IBS, referring to the development of IBS symptoms -- particularly abdominal pain and diarrhea -- shortly after an enteric infection, is based on research from prospective studies in which IBS symptoms developed in 7% to 32% of patients after they recovered from bacterial gastroenteritis.[52,55,56] Specific risk factors for the development of PI-IBS have been identified, including younger age, female sex, presence of severe infectious gastroenteritis for a prolonged period, use of antibiotics to treat this infection, and presence of concomitant psychological disorders (eg, anxiety).[39,52,55,57] Difficulty in downregulating intestinal inflammation in the colonic mucosa has been suggested as a potential underlying mechanism in this condition.[52] Also suggested as a potential underlying mechanism is the presence of colonic changes shown in patients with PI-IBS compared with controls, including increased gut permeability, increased mucosal enterochromaffin cell production, and increased concentration of mast cells and T lymphocytes in the gut mucosa.[39,52,55,57] Despite considerable evidence linking IBS with an inflammatory etiology (perhaps triggered by enteric infection), in a controlled trial of patients with PI-IBS, anti-inflammatory treatment with prednisolone was not more effective than placebo in improving patient symptoms.[58] The true role of prior infection as a key factor in PI-IBS remains to be established.[59]

The use of probiotics (products containing live or attenuated bacteria that have a positive effect on the host) in alleviating symptoms in patients with PI-IBS is an area of recent focus.[60,61] The potential utility of probiotics in this setting stems from their antibacterial, antiviral, and immune-modulating properties; their ability to modify intestinal flora; and their potential to enhance intestinal mucus secretion or influence stool consistency or volume and gas handling.[60] The number of studies evaluating the efficacy of probiotic preparations in patients with IBS is limited but growing.[60-68] Because trials vary in study design, dose, and strain (Lactobacillus and Bifidobacteria alone or in combination; mixture of Lactobacillus, Bifidobacteria, and Streptococcus), direct comparison of results is challenging. Overall, some degree of IBS symptom improvement has been demonstrated in symptoms such as abdominal pain,[65,66] bloating,[63,66] gas,[66] and daily symptom scores.[62,65] O'Mahoney and colleagues[60] have recently demonstrated that results with the Bifidobacterium infantis strain are particularly promising. In a separate analysis, these investigators showed that the baseline characteristics of urgency and hard stool increased the odds ratio of response to this strain, whereas straining and alcohol consumption reduced the likelihood of response.[69,70] The ultimate place in therapy of probiotics in IBS remains to be elucidated.

Small Intestinal Bacterial Overgrowth
The presence of a higher than usual population of bacteria in the small intestine (leading to bacterial fermentation of poorly digestible starches and subsequent gas production) has been proposed as a potential etiologic factor in IBS.[71] Pimentel and colleagues have shown that, when measured by the lactose hydrogen breath test (LHBT), small intestinal bacterial overgrowth (SIBO) has been detected in 78% to 84% of patients with IBS.[71,72] However, the accuracy of the LHBT in testing for the presence of SIBO has been questioned.[73] Sensitivity of the LHBT for SIBO has been shown to be as low as 16.7%, and specificity approximately 70%.[74] Additionally, this test may suboptimally assess treatment response.[75] The glucose breath test has been shown to be a more reliable tool,[76] with a 75% sensitivity for SIBO[77] vs 39% with LHBT for the "double-peak" method of SIBO detection.[74] In a recently conducted retrospective study involving review of patient charts for the presence of gastrointestinal-related symptoms (including IBS) in patients who were referred for glucose hydrogen breath tests for SIBO, of 113 patients who met Rome II criteria for IBS, 11% tested positive for SIBO.[78] Thus, results demonstrated that IBS symptoms are often unrelated to the presence of SIBO. Despite the controversy regarding the contribution of SIBO to the underlying pathophysiology of IBS and its symptoms, short-term placebo-controlled clinical studies with select antibiotics, including neomycin and rifaximin, have demonstrated symptom improvement in IBS patients.[61,72,79] Antibiotics may therefore have potential utility in select subgroups of IBS patients in whom SIBO contributes to symptoms. However, the chronic nature of IBS symptoms often leads to the need for long-term treatment. Given the fact that long-term use of antibiotics is generally undesirable, the place of antibiotics in IBS therapy remains to be established.[73]

Food Intolerance
Food intolerance has been proposed as a potential cause of GI symptoms in some patients with IBS; however, this link is not well established. Although some patients associate onset of IBS symptoms with ingestion of particular foods, identification of a true food intolerance is challenging, and elimination diets are typically time-consuming and difficult to implement. Recent research involving exclusion of foods to which patients had immunoglobulin (Ig) G antibodies, which are associated with a more delayed response after antigen exposure than IgE antibodies, resulted in significantly better symptom improvement than in patients in the nonexclusion group.[80] Further research into the role of food intolerance in IBS is warranted.

Serotonin Signaling The effect of serotonergic mechanisms in the manifestation of IBS symptoms has led to development of a new drug class for the treatment of IBS patients: the GI serotonergic agents.

Normal GI function relies on a properly functioning brain-gut axis, which involves the coordinated interplay of the GI musculature, the CNS, the autonomic nervous system, and the enteric nervous system (ENS). The ENS contains millions of neurons embedded in the wall of the digestive tract and functions, at least in part, independently of the CNS. The size, complexity, and independent function of the ENS has resulted in application of the terms "the second brain" and "the mini-brain."[81] Impaired function or coordination of any of these systems, or the communication between these systems and the GI musculature, can lead to symptoms of dysmotility and altered sensory perception, which are characteristic of IBS and select other GI motility disorders.[82]

The neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) is a predominant signaling molecule in the ENS. Most (90% to 95%) of the body's serotonin is found in the gut, and smaller amounts are found in the brain (about 3%) and in platelets (about 2%).[83] In the GI tract, serotonin facilitates communication between the ENS and its effector systems (muscles, secretory endothelium, endocrine cells, and vasculature of the GI tract), thus playing a key role in normal GI tract functioning.[84] In addition, serotonin plays a role in the communication between the ENS and the CNS.

In the gut, serotonin is synthesized by and stored in the enterochromaffin cells, which are located within the mucosa of the intestinal wall. When material passes through the lumen and the mucosa is stimulated, enterochromaffin cells release serotonin, which then binds to its receptors (primarily 5-HT1P receptors) on intrinsic primary afferent neurons, initiating peristalsis and secretion. Serotonin also binds to 5-HT4 receptors on interneurons, which augments the transmission of signals to motor neurons, resulting in enhanced peristaltic activity. In transgenic mice lacking 5-HT4 receptors, colonic motility is abnormally slow, confirming the role of these receptors in facilitating normal colonic motility.[85] By binding to 5-HT3 receptors on efferent sensory innervations coming from the vagus and the spinal nerves, serotonin mediates signaling between the ENS and the CNS and, thus, modulates pain perception.

To regulate the signaling process, excess serotonin must be removed; this is accomplished by the SERT molecule expressed by intestinal epithelial cells.[86] Human studies have shown that defects in serotonin signaling contribute to the pathophysiology of IBS and, potentially, other GI motility disorders. In a recent study by Coates and colleagues,[87] biopsy specimens from patients with IBS showed significantly lower mucosal serotonin concentrations than those from healthy controls, potentially the result of lower mRNA levels for tryptophan hydroxylase (the rate-limiting enzyme in serotonin synthesis), which were also significantly lower in patients with inflammatory bowel disease.[87] There was no significant difference in the number of enterochromaffin cells or in the capacity of these cells to release serotonin under stimulated conditions. In another study, higher serotonin levels were observed in mucosal biopsy samples from patients with IBS with constipation (IBS-C) than in patients with IBS-D or in healthy volunteers.[88]

Serotonin levels may also be affected by altering the amount or function of SERT. The study by Coates and colleagues[87] showed a significant decrease in the level of SERT mRNA and SERT protein expressed in the intestinal epithelial cells of IBS patients compared with that of healthy volunteers. In another study,[89] SERT expression and binding capacity in platelets were decreased in women with IBS-D compared with expression and binding capacity in healthy controls. Furthermore, Chen and colleagues[90] showed that mice with a SERT gene deletion had altered colonic motility. It is interesting to note that the mice thrived in laboratory housing conditions, indicating that other transporters could compensate for the lack of SERT. Additional studies have focused on SERT polymorphisms. Yeo and colleagues[91] showed an association between patients with IBS-D and the homozygous short polymorphism of the SERT gene promoter. This mutation results in lower levels of SERT gene transcription and reduced amounts of SERT protein available for reuptake of serotonin. In addition, Camilleri and colleagues[92] showed a possible link between the long promoter polymorphism and patient response to therapy.

Thus, a substantially large body of work shows that normal gut physiology is predicated on the interplay between the GI musculature and the ENS, autonomic nervous system, and CNS. One of the central mediators of this complex interplay is the neurotransmitter serotonin. Impairment or imbalance in serotonergic signaling, which can affect GI motility, secretion, and visceral sensitivity, may be affected by defects or deficiencies in serotonin production, specific serotonin receptors, or proteins such as SERT. These changes can manifest in symptoms associated with IBS, including abdominal pain, altered bowel habits (constipation, diarrhea, or alternation between these 2 states), and bloating."

http://www.medscape.com/viewarticle/532089_print

Gastroenterology. 2007 Jan;132(1):397-414.The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders.Gershon MD, Tack J.
Department of Pathology & Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York.

Serotonin is an important gastrointestinal signaling molecule. It is a paracrine messenger utilized by enterochromaffin (EC) cells, which function as sensory transducers. Serotonin activates intrinsic and extrinsic primary afferent neurons to, respectively, initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is also a neurotransmitter utilized by a system of long descending myenteric interneurons. Serotonin is synthesized through the actions of 2 different tryptophan hydroxylases, TpH1 and TpH2, which are found, respectively, in EC cells and neurons. Serotonin is inactivated by the serotonin reuptake transporter (SERT)-mediated uptake into enterocytes or neurons. The presence of many serotonin receptor subtypes enables selective drugs to be designed to therapeutically modulate gastrointestinal motility, secretion, and sensation. Current examples include tegaserod, a 5-HT(4) partial agonist, which has been approved for treatment of irritable bowel syndrome (IBS) with constipation in women and for chronic constipation in men and women. The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea. Serotonergic signaling abnormalities have also been putatively implicated in the pathogenesis of functional bowel diseases. Other compounds, for which efficacy has not been rigorously established, but which may have value, include tricyclic antidepressants and serotonin selective reuptake inhibitors to combat IBS, and 5-HT(1) agonists, which enhance gastric accommodation, to treat functional dyspepsia. The initial success encountered with serotonergic agents holds promise for newer and more potent insights and therapies of brain-gut disorders.

PMID: 17241888

http://www.usnews.com/usnews/health/articl.../6healthweb.htm


Expert Opin Investig Drugs. 2007 Jun;16(6):761-5.5-HT and the brain-gut axis: opportunities for pharmacologic intervention.Crowell MD, Wessinger SB.
Interactions between the enteric nervous system of the gut and the brain occur bidirectionally over sympathetic and parasympathetic pathways. Coordinated actions of the central, autonomic and enteric nervous systems modulate intestinal motor, sensory and secretory activities by neuromodulators, including 5-HT, noradrenaline and dopamine. 5-HT is an important signaling molecule in the brain-gut axis and the 5-HT released from enterochromaffin cells modulates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. Irritable bowel syndrome is associated with altered motility, secretion and sensation; enteric 5-HT signaling may be defective in this disorder. In this editorial, recent data are reviewed and the potential for the development of pharmacologic intervention is assessed.

PMID: 17501688

Neurogastroenterol Motil. 2007 May 21; [Epub ahead of print]
Sigmoid-colonic motility in health and irritable bowel syndrome: a role for 5-hydroxytryptamine.Houghton LA, Atkinson W, Lockhart S, Fell C, Whorwell PJ, Keevil B.
Neurogastroenterology Unit, Academic Division of Medicine and Surgery, Wythenshawe Hospital, Manchester, UK.

Evidence suggests that sigmoid-colonic motility is increased in patients with irritable bowel syndrome (IBS). 5-Hydroxytryptamine (5-HT) plays a role in the control of motility, but its involvement in the dysmotility seen in IBS remains unclear. To investigate the relationship between platelet depleted plasma 5-HT (PDP 5-HT) concentration and sigmoid-colonic motility in patients with IBS and healthy volunteers. Pre- and postprandial PDP 5-HT concentrations were assessed while recording sigmoid-colonic motility in 35 IBS patients (aged 19-53 years, eight male) and 16 healthy volunteers (aged 18-39 years, six male). Motility was recorded using a five-channel solid-state catheter introduced to a depth of 35 cm into an unprepared bowel. 5-Hydroxytryptamine concentration was measured by reverse-phase HPLC with fluorimetric detection. Irritable bowel syndrome patients had elevated concentrations of PDP 5-HT under fasting (P < 0.004) and fed (P = 0.079) conditions compared with controls. Likewise, they exhibited increased sigmoid-colonic motility under fasting (activity index: P < 0.02) and fed (P < 0.05) conditions compared with controls. Platelet depleted plasma 5-HT concentration positively correlated with colonic activity index under both fasting (r = 0.402; P = 0.003) and fed (r = 0.439; P = 0.001) conditions. These data show a possible relationship between endogenous concentrations of 5-HT and sigmoid-colonic motility recorded in both IBS and healthy subjects.

PMID: 17539895


Neurogastroenterol Motil. 2007 Aug;19 Suppl 2:13-8.
Importance of 5-hydroxytryptamine receptors on intestinal afferents in the regulation of visceral sensitivity.Greenwood-van Meerveld B.
Veteran's Affairs Medical Center and Oklahoma Center for Neuroscience, University of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA. beverley-greenwood@ouhsc.edu

Serotonin (5-HT) plays an important role as a signalling molecule in the gastrointestinal (GI) tract. The regulation of GI sensitivity via 5-HT is mediated by specific 5-HT receptor subytypes on intrinsic and extrinsic afferents. This review discusses visceral afferent hypersensitivity in irritable bowel syndrome (IBS) and the importance of 5HT(3), 5HT(4), and 5HT(2B) receptor-mediated mechanisms in the regulation of visceral sensitivity.

PMID: 17620083


Neurogastroenterol Motil. 2007 Aug;19 Suppl 2:19-24.
Serotonin and neuroprotection in functional bowel disorders.Gershon MD, Liu MT.
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA. mdg4@columbia.edu

The 5-HT(4) partial agonist tegaserod is effective in the treatment of chronic constipation and constipation predominant irritable bowel syndrome. 5-HT(4) receptors are located on presynaptic terminals in the enteric nervous system. Stimulation of 5-HT(4) receptors enhances the release of acetylcholine and calcitonin gene related peptide from stimulated nerve terminals. This action strengthens neurotransmission in prokinetic pathways, enhancing gastrointestinal motility. The knockout of 5-HT(4) receptors in mice not only slows gastrointestinal activity but also, after 1 month of age, increases the age-related loss of enteric neurons and decreases the size of neurons that survive. 5-HT(4) receptor agonists, tegaserod and RS67506, increase numbers of enteric neurons developing from precursor cells and/or surviving in culture; they also increase neurite outgrowth and decrease apoptosis. The 5-HT(4) receptor antagonist, GR113808, blocks all of these effects, which are thus specific and 5-HT(4)-mediated. 5-HT(4) receptor agonists, therefore, are neuroprotective and neurotrophic for enteric neurons. Because the age-related decline in numbers of enteric neurons may contribute to the dysmotilities of the elderly, the possibility that the neuroprotective actions of 5-HT agonists can be utilized to prevent the occurrence or worsening of these conditions should be investigated.

PMID: 17620084


Neurogastroenterol Motil. 2007 Aug;19 Suppl 2:25-31.
Recent advances in understanding the role of serotonin in gastrointestinal motility in functional bowel disorders: alterations in 5-HT signalling and metabolism in human disease.Spiller R.
Professor of Gastroenterology, Wolfson Digestive Diseases Centre, Nottingham, UK. robin.spiller@nottingham.ac.uk

Serotonin (5-hydroxytryptamine, 5-HT) is present in abundance within the gut, most stored in enterochromaffin cell granules. It is released by a range of stimuli, most potently by mucosal stroking. Released 5-HT stimulates local enteric nervous reflexes to initiate secretion and propulsive motility. It also acts on vagal afferents altering motility and in large amounts induces nausea. Rapid reuptake by a specific transporter (serotonin transporter, SERT) limits its diffusion and actions. Abnormally increased 5-HT is found in a range of gastrointestinal disorders including chemotherapy-induced nausea and vomiting, carcinoid syndrome, coeliac disease, inflammatory bowel disease and irritable bowel syndrome (IBS) with diarrhoea (IBS-D), especially that developing following enteric infection. Impaired SERT has been described in IBS-D and might account for some of the increase in mucosal 5-HT availability. 5-HT(3) receptor antagonists inhibit chemotherapy-induced nausea and diarrhoea associated with both carcinoid syndrome and IBS. While IBS-D is associated with increased 5-HT postprandially, IBS with constipation (IBS-C) is associated with impaired 5-HT response and responds to 5-HT(4) agonists such as Prucalopride and 5-HT(4) partial agonists such as Tegaserod.

PMID: 17620085

Neurogastroenterol Motil. 2007 Aug;19 Suppl 2:40-5.
Pharmacogenomics and serotonergic agents: research observations and potential clinical practice implications.Camilleri M.
CENTER Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. camilleri.michael@mayo.edu

Pharmacogenomics of serotonin are potentially relevant in research and clinical practice. There are few proven examples of the importance of pharmacogenetics of serotonin-modifying agents used in functional gastrointestinal or motility disorders. Drug metabolism is dependent on function of the cytochrome P450 enzymes, such as 2D6 and 3A4. Genetic variations in transporters and translation mechanisms have been associated with responses to treatment in irritable bowel syndrome and in obesity. Research on the impact of polymorphisms of key proteins on the pharmacokinetics and pharmacodynamics of drugs that alter serotonin-mediated signalling will assist in explaining diverse responses to those drugs and ultimately improve clinical practice, individualizing medicine.

PMID: 17620087

Chin Med J (Engl). 2007 Dec 5;120(23):2069-74.
Expression and role of 5-HT7 receptor in brain and intestine in rats with irritable bowel syndrome.Zou BC, Dong L, Wang Y, Wang SH, Cao MB.
Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, China.

BACKGROUND: The 5-hydroxytryptamine7 receptor (5-HT(7) receptor, 5-HT(7)R) plays an important role in the regulation of smooth muscle relaxation and visceral sensation and might be involved in the pathogenesis of the gastrointestinal dyskinesia, abdominal pain and visceral paresthesia in irritable bowel syndrome (IBS). The aim of this study was to investigate the role of the 5-HT(7) receptor in the pathogenesis of IBS. METHODS: A rat model of irritable bowel syndrome with diarrhea (IBS-D) was established by colonic instillation of acetic acid and restraint stress. A rat model with irritable bowel syndrome with constipation (IBS-C) was established by stomach irrigated with 0 - 4 degrees C cool water daily for 14 days. The content and distribution of 5-HT in the brain and gut were examined by immunohistochemistry and the mRNA expression of the 5-HT(7) receptor was determined by fluorescent quantitative reverse transcription polymerase chain reaction. The accumulation of cyclic adenosine monophosphate (cAMP) in all the same tissues was measured by radioimmunity. RESULTS: The models of IBS were reliable by identification. The immunohistochemistry results showed that there were significantly more 5-HT positive cells in the IBS-D group than in the control group in the hippocampus, hypothalamus, jejunum, ileum, proximate colon and distal colon (P < 0.05), as well as more than were found in the IBS-C group in jejunum and ileum (P < 0.05). There were more 5-HT positive cells in the IBS-C group than in the control hippocampus, hypothalamus, ileum, proximate colon, and distal colon (P < 0.05). Real time-PCR results showed that the expression level of the 5-HT(7) receptor in both the IBS-C and IBS-D groups were enhanced compared with the control group in the hippocampus and hypothalamus (P < 0.05). The expression level of 5-HT(7) receptors in the IBS-C group was notably greater when compared with the controls in the ileum and colon (P < 0.05). The cAMP accumulation in the hippocampus and hypothalamus in both the IBS-C and IBS-D groups was higher than that in the control group (P < 0.01 and P < 0.05). The cAMP accumulation in the IBS-C group was higher than that in the control group in the proximal and distal colon (P < 0.05). CONCLUSIONS: The increased 5-HT content in the brain and intestine is related to the IBS pathogenesis. The up-regulated expression of the 5-HT(7) receptor in the brain and colon might play an important role in the pathogenesis of IBS-C.

PMID: 18167178

World J Gastroenterol. 2007 Dec 7;13(45):6041-7. Links
Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome.Wang SH, Dong L, Luo JY, Gong J, Li L, Lu XL, Han SP.
Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, 157, Xi 5 Road, Xi'an 710004, Shaanxi Province, China. donglei4488@sina.com.

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography-electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 +/- 90, 122 +/- 54, 61 +/- 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 +/- 84, 188 +/- 91, and 93 +/- 45 ng/mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 +/- 9.4 and 35.8 +/- 5.5/high power field (hpf), respectively, which were significantly more than that in the normal group (29.8 +/- 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 +/- 9.4, 35.8 +/- 5.5, 29.8 +/- 4.4/hpf, respectively) than at the duodenum (19.6 +/- 4.7, 18.5 +/- 6.3, 19.2 +/- 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

PMID: 18023097 [PubMed - in process]

Cell Mol Life Sci. 2007 Dec 15 [Epub ahead of print] Links
Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives.Lesurtel M, Soll C, Graf R, Clavien PA.
Swiss HPB Center, Department of Visceral and Transplant Surgery, University Hospital of Zurich, Rämistrasse 100, CH-8091, Zürich, Switzerland, clavien@chir.unizh.ch.

Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases.

PMID: 18080089

Gastroenterology. 2007 Jan;132(1):397-414. Links
The serotonin signaling system: from basic understanding to drug development for functional GI disorders.Gershon MD, Tack J.
Department of Pathology & Cell Biology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA. mdg4@columbia.edu

Serotonin is an important gastrointestinal signaling molecule. It is a paracrine messenger utilized by enterochromaffin (EC) cells, which function as sensory transducers. Serotonin activates intrinsic and extrinsic primary afferent neurons to, respectively, initiate peristaltic and secretory reflexes and to transmit information to the central nervous system. Serotonin is also a neurotransmitter utilized by a system of long descending myenteric interneurons. Serotonin is synthesized through the actions of 2 different tryptophan hydroxylases, TpH1 and TpH2, which are found, respectively, in EC cells and neurons. Serotonin is inactivated by the serotonin reuptake transporter (SERT)-mediated uptake into enterocytes or neurons. The presence of many serotonin receptor subtypes enables selective drugs to be designed to therapeutically modulate gastrointestinal motility, secretion, and sensation. Current examples include tegaserod, a 5-HT(4) partial agonist, which has been approved for treatment of irritable bowel syndrome (IBS) with constipation in women and for chronic constipation in men and women. The 5-HT(3) antagonists, granisetron and ondansetron, are useful in combating the nausea associated with cancer chemotherapy, and alosetron is employed in the treatment of IBS with diarrhea. Serotonergic signaling abnormalities have also been putatively implicated in the pathogenesis of functional bowel diseases. Other compounds, for which efficacy has not been rigorously established, but which may have value, include tricyclic antidepressants and serotonin selective reuptake inhibitors to combat IBS, and 5-HT(1) agonists, which enhance gastric accommodation, to treat functional dyspepsia. The initial success encountered with serotonergic agents holds promise for newer and more potent insights and therapies of brain-gut disorders.

PMID: 17241888

Biol Res Nurs. 2007 Oct;9(2):161-9. Links
Relationship of SERT polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome.Jarrett ME, Kohen R, Cain KC, Burr RL, Poppe A, Navaja GP, Heitkemper MM.
Department of Biobehavioral Nursing & Health Systems, University of Washington, Seattle, Washington 98195-7266, USA. jarrett@u.washington.edu

This study investigates the association of psychological symptoms with the distribution of two serotonin transporter gene (SERT) polymorphisms, located in the promoter region (5-HTTLPR) and in intron 2 (STin2 VNTR), in patients with irritable bowel syndrome (IBS). Participants, 21 men and 117 women, were assessed for mental health history and current psychological distress. A blood sample was used for genotyping. Participants who were homozygous for the short allele of 5-HTTLPR or carried a STin2.9 VNTR allele were significantly more likely to have a history of depression. Participants did not differ by genotype in their history of anxiety or suicidal ideation nor in their current levels of depression, anxiety, or general psychological distress. The results support a biopsychosocial model of IBS in which SERT genotype modifies the risk for depressive episodes. Long term, practitioners may individualize treatment of patients with IBS using genotype as one of the factors.

PMID: 17909168



Neurogastroenterol Motil. 2008 Jan 13 [Epub ahead of print]
Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model.o'mahony S, Chua AS, Quigley EM, Clarke G, Shanahan F, Keeling PW, Dinan TG.
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.

Efforts to define either a biomarker for irritable bowel syndrome (IBS) or a valid animal model have proven disappointing. The aims of this study were to determine if buspirone stimulates prolactin release through the 5-hydroxytryptamine (5HT)1a receptor and whether this response is altered in patients with IBS and in the rat maternal separation model. Buspirone (30 mg) was used to stimulate prolactin release in 40 patients with IBS and in 40 healthy controls. In study 1, 10 IBS patients and 10 controls underwent pretreatment with pindolol (5HT1a antagonist) or placebo followed by buspirone. In study 2, 30 patients with IBS and 30 healthy controls had prolactin release stimulated by buspirone. Maternally separated and nonseparated rats were also treated with buspirone and prolactin monitored. Serotonin metabolites were measured together with the expression of the 5HT1a and serotonin transporter (SERT) gene. Pindolol produced a dose-dependent decrease in the buspirone prolactin response. Patients with IBS and maternally separated rats showed an exaggerated release of prolactin in response to buspirone. In the animal model, an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene. In conclusion altered central serotonin responses are found in both IBS and in an animal model.

PMID: 18194152

Clin Gastroenterol Hepatol. 2008 Jan 30 [Epub ahead of print]
Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Andresen V, Montori VM, Keller J, West CP, Layer P, Camilleri M.
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program; Department of Internal Medicine, Israelitic Hospital, University of Hamburg, Germany.

BACKGROUND & AIMS: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT(3)) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). METHODS: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT(3) antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. RESULTS: We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT(3) antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval [CI], 1.49-1.72; I(2) = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I(2) = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I(2) = 65%); there was less constipation with 5-HT(3) antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT(3) antagonists had possible ischemic colitis versus none in control groups. CONCLUSIONS: 5-HT(3) antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT(3) antagonists, although the risk is lower in those with D-IBS.

PMID: 18242143


J Gastroenterol Hepatol. 2007 Dec;22(12):2330-7. Links
Plasma and gastric mucosal 5-hydroxytryptamine concentrations following cold water intake in patients with diarrhea-predominant irritable bowel syndrome.Zuo XL, Li YQ, Yang XZ, Guo M, Guo YT, Lu XF, Li JM, Desmond PV.
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, China.

BACKGROUND AND AIM: The purpose of the present paper was to investigate the effects of cold water intake on 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in diarrhea-predominant irritable bowel syndrome (d-IBS) patients, and to observe the relationship between 5-HT and symptomatology. METHODS: The plasma 5-HT/5-HIAA concentrations at 0, 30 min, 60 min, 90 min, 120 min, 150 min and 180 min following cold or warm water intake were investigated in 32 female subjects with d-IBS and 21 healthy female subjects. Gastric mucosal 5-HT under fasting conditions and following water intake were further investigated in 15 d-IBS patients and nine healthy subjects. Symptomatology was assessed throughout the study. RESULTS: The plasma 5-HT concentrations in IBS patients were significantly higher than those of controls at 30 min (P = 0.022), 60 min (P < 0.001), 90 min (P < 0.001), 120 min (P < 0.001) and 150 min (P = 0.001) after cold water intake. The peak plasma 5-HT/5-HIAA and area under the curve for 5-HT/5-HIAA were also higher in d-IBS patients (P < 0.001). Gastric mucosal 5-HT in d-IBS patients and controls did not show any significant differences both under fasting condition (P = 0.596) and after cold water intake (P = 0.426). Last, the d-IBS patients with symptoms had higher 5-HT concentration (P < 0.001) and there was a positive correlation (r = 0.714, P = 0.001)between the symptomatology and plasma 5-HT level. CONCLUSIONS: These data suggest that symptomatology following cold water intake may be associated with increased plasma 5-HT concentrations in female subjects with d-IBS.

PMID: 18265445


J Gastroenterol. 2006 Apr;41(4):311-7. Links
Visceral hypersensitivity following cold water intake in subjects with irritable bowel syndrome.Zuo XL, Li YQ, Shi L, Lv GP, Kuang RG, Lu XF, Li JM, Desmond PV.
Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan 250012, China.

BACKGROUND: Visceral hypersensitivity has been shown to be present in irritable bowel syndrome (IBS). This study sought to investigate rectal sensitivity and abdominal symptoms in IBS patients before and after 220 ml cold water intake. METHODS: A total of 60 IBS patients and 18 healthy controls participated in this study. Both the perception thresholds and defecation thresholds to rectal balloon distension were measured. Then, all subjects were asked to drink 220 ml 37 degrees C warm water or 4 degrees C cold water, and these steps were repeated 20 min later. Symptoms including abdominal pain/discomfort, bloating, and diarrhea were recorded during the study. RESULTS: Compared with the controls, the thresholds of initial sensation to rectal balloon distention in IBS patients were significantly lower while the defecation thresholds were higher in constipation-predominant IBS patients. After drinking cold water, the perception thresholds in IBS patients and the defecation thresholds in diarrhea-predominant IBS patients were further decreased. However, warm water intake did not change the perception thresholds significantly in either IBS patients or controls. A negative linear correlation was found between the symptoms and the visceral perception thresholds in diarrhea-predominant IBS patients who showed significant symptoms after cold water intake. CONCLUSION: The results indicated that cold water intake leads to lowered visceral perception thresholds in IBS patients that were inversely relevant to the abdominal symptoms in symptomatic diarrhea-predominant IBS patients. The alteration of rectal sensitivity and abdominal symptoms following cold water stimulation provided further objective evidence for visceral hypersensitivity in IBS patients.

PMID: 16741609 [PubMed - indexed for MEDLINE]


The Experts Speak
At IFFGD's 7th International Symposium on Functional Gastrointestinal Disorders in April 2007, we had the opportunity to talk to some of the international experts in functional GI disorders. Our discussions covered some of the most recent developments in this field. Click the topic titles below to go to the video interviews!

Video Corner: Serotonin

Increasingly our understanding of IBS is that it is a heterogeneous disorder – that is, multiple factors contribute to the well defined symptoms of the disorder. One of these suspected underlying dysfunctions involves serotonin, which is a neurotransmitter or messenger to nerves. Most serotonin in the body is in cells that line the gut where it senses what is going on and through receptors signals nerves that stimulate a response. The serotonin must then be reabsorbed (a process called re-uptake) into cells. This process appears to be disrupted in people with IBS.

Serotonin
How does serotonin affect gut function? An interview with Gary M. Mawe, PhD, Professor of Anatomy and Neurobiology, University of Vermont, Burlington, VT. Dr. Mawe is a basic scientist.

http://www.aboutibs.org/site/learning-cent...orner/serotonin

http://www.aboutibs.org/site/learning-center/video-corner/

The above are videos for the public on serotonin and IBS.
I am not a doctor. All information I present is for educational purposes only and should not be subsituted for the advise of a qualified health care provider.

Please make sure you have your symptoms diagnosed by a medical practitioner or a doctor.

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