Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome

Abstract

EDITORS, I have read with great interest the systematic review with meta- analysis written by Ianiro and co-workers,1 in which the authors have evaluated the efficacy of faecal microbiota transplantation (FMT, or bacteriotherapy) for the treatment of irritable bowel syndrome (IBS). Although only a handful of studies were eligible to be included in this meticulous analysis, the authors implied that donor stool delivered via colonoscopy/nasojejunal tube may be useful in IBS whereas no ben- efis were seen with autologous stool. A subgroup analysis revealed a potential advantage on IBS symptoms when stool transplant was administered via the lower gastrointestinal tract. Despite many open questions of interpretation, an affirmative link between FMT and IBS could be attributed to the specific microbial mass transplanted.1,2 I agree with this sound inference, and present here a reasonable hy- pothesis that the beneficial effects might be due to FBT-driven mod- ulation of hydrogen-producing microbiota in IBS. Hydrogen gas (H2) is continuously produced by many members of gut flora and subsequently utilised by cross-feeding microbes for growth and metabolism. A possible disbalance in intestinal H2 turnover could have many detrimental effects on human health,3,4 either when gut hydrogen is abundant or deficient. Specifically, diarrhoea-predominant IBS appears to be associated with the over- production of H2 due to small intestine gut dysbiosis.5 Theoretically, hydrogen surplus in IBS could be attributed to the high abundance of hydrogen-releasing bacteria (such as Clostridium, Tissierella, and Prevotella) and/or a comparative dearth of hydrogenotrophs (eg sulphate-reducing bacteria, methanogens, acetogens). This supposition lies in line with recent trials where increased levels in Clostridium clusters accompanied by the low abundance of methanogens were found in faecal samples of IBS patients comparing to healthy con- trols.6,7 This perhaps vindicates a rationale for a bacteriotherapy to restore gut H2 homeostasis in IBS. For example, a recent study has shown that FBT with donor material containing an abundance of butyrate-producing bacteria may rebuild the gut microbiota ecosystem in IBS,8 which with hydrogenotrophic microbial communities could influence butyrate output and consequently diminish biohydrogen synthesis.9 Luminal H2 concentrations before and after FBT in patients with IBS have not been measured so far so no evidence is currently available to back up the above supposition. Further studies are thus warranted to confirm a disequilibrium between H2-producing and -consuming gut flora as a possible therapeutic target in IBS. These need to scrutinise advantages of FBT to counterbalance H2 excess in patients with IBS while accounting for diverse microbial profiles of donors and patients, IBS subtypes, working protocols and routes of FMT administration, and types of control intervention, in well-designed robust long-term RCTs.

Study details

Article type

Letter

Disease / injury model

Irritable Bowel Syndrome (IBS)

Dose-dependent effect

No

Outcome

Neutral

Findings

The article hypothesizes that the beneficial effects of faecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) may be due to modulation of hydrogen-producing microbiota, suggesting that balancing gut hydrogen could be a therapeutic target. However, it notes that direct evidence is lacking and calls for further studies.