Short chain fatty acids, including butyrate, proprionate, and lactate, are generated in the colon as result of bacterial fermentation of dietary fibre by luminal bacteria such as Bifidobacterium, Eubacterium, and Lactobacillus species. Roediger et al demonstrated significant inhibition of butyrate but not glucose oxidation by hydrogen sulphide in the ascending colon, splenic flexure, and in the rectosigmoid region.15 A direct anti-inflammatory effect for butyrate, the most extensively studied of the short chain fatty acids, may be attributable to its inhibition of nuclear factor κB, thus preventing the transcript
ion of proinflammatory cytokines.16 In this study, butyrate also attenuated dextran sulphate sodium (DSS) induced colitis. Furthermore, butyrate has been demonstrated to reduce colonic permeability by enhancing peroxisome proliferator activated receptor γ (PPAR-γ) activation.17 This is of special interest as PPAR-γ ligands show antineoplastic and anti-inflammatory effects in experimental colitis.18
Patients with active extensive UC have decreased colonic butyrate oxidation. As remission of disease is associated with normalisation of butyrate oxidation, UC mucosa is not intrinsically altered in butyrate oxidation.19 Butyrate enemas have been shown to be of benefit in the management of distal UC.20,21
So, how to increase faecal butyrate levels? In animal and human studies, ingestion of resistant fibre has resulted in an increase in the population of Bifidobacillus and Lactobacillus in the colon and an increase in faecal butyrate concentrations. Administration of oat bran over three months to UC patients in remission (corresponding to 20 g dietary fibre) has recently been shown to result in increased faecal butyrate levels and in this pilot study no relapses were observed.22 Alternative strategies of delivering short chain fatty acids to the inflamed colon are by providing a substrate, a “prebiotic”, for short chain fatty acid production by colonic bacteria, or directly delivering probiotics to the intestinal lumen.
PREBIOTICS IN UC: EFFECTIVE VIA BUTYRATE INDUCTION?
Prebiotics are defined as non-digestible food ingredients that beneficially affect the host by selectively stimulating the growth or activity of bacterial species already present in the gut. A germinated barley foodstuff (GBF) which contains hemicellulose rich fibre and glutamine rich protein has been shown to attenuate inflammation in DSS, trinitrobenzene sulphonic acid (TNBS), and HLA-B27 transgenic animal models of colitis.23 In DSS colitis, GBF suppressed significantly serum interleukin 6 levels and mucosal STAT-3 expression. These effects may be caused by increased faecal butyrate production.24 GBF has been demonstrated to improve disease activity in a small pilot study in patients with active UC.25 In a controlled small study investigating 18 patients with active UC, patients were treated with baseline anti-inflammatory treatment with or without GBF. GBF therapy resulted in a significantly better outcome and was associated with increased faecal concentrations of Bifidobacterium and Eubacterium limosum.26 Another important study in the area of prebiotic and dietary fibre has been performed by a Spanish collaborative group.27 In this large study, Plantago ovata seeds (dietary fibre 20 g/day) was compared with mesalamine in the maintenance of remission in patients with UC (n = 105). Treatment failure rate was 40% in the Plantago ovata seed group, 35% in the mesalamine group, and 30% in the Plantaga ovata plus mesalamine group. A significant increase in faecal butyrate levels was observed after Plantago ovata seed administration. The same preparation was also shown to ameliorate colonic damage in HLA-B27 transgenic rats and this effect was also associated with increased production in short chain fatty acids.28 Therefore, most of prebiotic products might exert their beneficial effects via modulating short chain fatty acid metabolism.