Ruminations on gut fermentation—any link to IBS?

The aetiology of irritable bowel syndrome (IBS), a disease that may affect at least 10% of the general population, continues to puzzle gastroenterologists and other scientists. While there is some evidence of perturbed gut microbiota in patients with IBS, microbiota profiles reliably linked to IBS remain to be identified. Meanwhile, studies of intestinal fermentation might hold the key to expanding our knowledge on the aetiology and management of IBS.

In a recent article in the American Journal of Gastroenterology, Rajilić-Stojanović et al. reviewed data on the impact of diet and the intestinal microbiota on IBS symptoms.¹ One of their important conclusions was that powerful interactions between distinct dietary patterns and intestinal microbial communities may—at least in part—be responsible for the fact that IBS has not yet been shown to be defined by certain microbiota profiles. As a lot of data going into studies exploring associations between microbiota profiles and disease conditions are cross-sectional, what we need to know much more about is how, including how quickly, changes in diet influences our gut microbiota, and therefore how resilient gut microbiota are to dietary changes.

A study that appeared in Gut earlier in 2015 was looking into just that issue. In their study, Halmos et al. considered whether differences in dietary FODMAP (fermentable oligo-, di-, monosaccharides and polyols) content reflect differences in the colonic luminal microenvironment.² Study participants (IBS patients and healthy controls) consumed their habitual diets for 1 week, but were subsequently switched to one of two challenge diets for 3 weeks (i.e. either a diet low in FODMAPs or a typical Australian diet). They were then allowed a wash-out period of 5 days, during which they consumed their habitual diets, and then later allocated to the alternative challenge diet for a further 3 weeks.

Halmos et al. found that the higher FODMAP content of the Australian diet compared with that of the low FODMAP or habitual diets was associated with specific stimulation of the growth of bacterial groups with putative health benefits, including butyrate-producers and mucus-associated Akkermansia muciniphila. This finding made the team speculate that long-term use of low-FODMAP diets should be used with caution, at least until the long-term effects of such diets on intestinal microbiota have been fully elucidated. To this end, a recent randomized controlled trial by Böhn et al. compared the effects of a diet low in FODMAPs with traditional dietary advice in patients with IBS. The findings of this study suggest that traditional IBS dietary advice is just as effective in terms of reducing IBS symptoms as adhering to a diet low in FODMAPs.³

In the study by Halmos et al., the concentration of short-chain fatty acids (SCFAs) in stool, which was used as a colonic health index, was independent of diet type.² The SCFAs acetate, propionate, and butyrate are produced primarily by bacterial fermentation of undigested carbohydrates (primarily dietary fibre aka ‘resistant starch’). The relevance of using the faecal SCFA concentration as a biomarker has, however, been questioned. Ringel–Kulka et al. looked into altered intestinal bacterial fermentation in the setting of IBS with regard to bowel characteristics and gastrointestinal symptoms.⁴ In their study, the primary aim was not merely to look at the distribution and composition of the microbiota, but to look at what the bacteria were actually doing. For this purpose, they looked at surrogate markers of gut bacterial fermentation, namely intestinal intraluminal pH and faecal SCFAs. Faecal SCFAs are naturally acidic and therefore cause a drop in the pH of the intestinal lumen. Compared with healthy controls, patients with IBS—independent of subtype—exhibited a significantly lower mean total colonic pH level, which could indicate higher intraluminal bacterial fermentation in this cohort. Of note, small-intestine pH levels did not differ between IBS patients and healthy controls, which suggests that bacterial fermentation is not increased in the small intestine of IBS patients. This finding may have important implications for understanding the contribution of small intestinal bacterial overgrowth (SIBO) in the pathophysiology of IBS. The SCFA levels in stool from IBS patients and healthy controls did not differ. Although this could be due to a number of circumstances, including differences in the absorption of SCFAs and colonic transit time, the authors do not recommend using faecal SCFAs as a marker for estimating intraluminal bacterial fermentation.

There seems to be an emerging focus on the role of SCFAs in intestinal health and disease. While the low-FODMAP diet used by some IBS patients is associated with reduced SCFA production, these fermented substances appear to have a central role in the prevention of colon cancer and possibly other diseases. The use of surrogate markers of fermentation may have taken us some way already in our search for aetiological factors, but we need to know more about the direct impact of changes in intestinal fermentation and the various molecules generated by these processes on the development and course of IBS. I look forward to discussing the impact on SCFAs on intestinal homeostasis specifically and public health in general in one or more future blog posts.

References

1. Rajilić-Stojanović M, Jonkers DM, Salonen A, et al. Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena? Am J Gastroenterol 2015; 110: 278–287. http://www.nature.com/ajg/journal/v110/n2/abs/ajg2014427a.html
2. Halmos EP, Christophersen CT, Bird AR, et al. Diets that differ in their FODMAP content alter the colonic lumincal microenvironment. Gut Epub ahead of print 12 July 2015 doi: 10.1136/gutjnl-2014-307264. http://gut.bmj.com/content/early/2014/07/12/gutjnl-2014-307264
3. Böhn L, Störsrud S, Liljebo T, et al. Diet low in FODMAPs reduces symptoms of irritable bowel syndrome as well as traditional dietary advice: A randomized controlled trial. Gastroenterology Epub ahead of print 5 August 2015. DOI: 10.1053/j.gastro.2015.07.054. http://www.gastrojournal.org/article/S0016-5085(15)01086-0/abstract?referrer=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpubmed%2F26255043
4. Ringel-Kulka T, Choi CH, Temas D, et al. Altered colonic bacterial fermentation as a potential pathophysiological factor in irritable bowel syndrome. Am J Gastroenterol 2015; 110: 1339–1346. http://www.nature.com/ajg/journal/v110/n9/full/ajg2015220a.html