Irritable bowel syndrome: Toward mechanistic subgroups

Recently, an (open-access) article co-authored with colleagues Hans Törnblom & Magnus Simrén appeared in Nature Reviews Gastroenterology and Hepatology – Crosstalk at the mucosal border: importance of the gut microenvironment in IBS.

This review addresses the complex pathophysiology of irritable bowel syndrome (IBS). We discuss four factors that may be involved:

  • Gut microbiota composition
  • Increased intestinal permeability
  • Imbalance in the enteroendocrine system
  • Perturbed immune system in the gut

The review makes a case that crosstalk locally at gut mucosal border might be important in how these four factors contribute to IBS symptoms.

The process might start with altered composition of the gut microbiota community, leading to an impaired intestinal barrier through degradation of epithelial tight junction proteins. The gut microbiota could also influence the activity of enteroendocrine cells, resulting in altered hormones in the gut and changes in immune cell activity.

In certain subgroups of IBS patients, symptoms could be initiated when an exogenous or endogenous trigger (not the gut microbiota) increases immune activity. This activity could potentially harm the epithelial barrier and the endocrine activity of the gut, helping the microbiota adhere to the gut mucosa. The immune system and its interactions with the nervous system might generate the IBS symptoms.

Below, I answer some questions from GMFH editors.

Why is the gastrointestinal mucosa such an important site in the body?

The lumen, the gastrointestinal tube, is really ‘outside’ on the inside of the body. Thus, the gastrointestinal mucosa is really facing the outside. The gastrointestinal mucosa comprises a very big area, often said to be the size a football field, where we have to be able to protect ourselves from any potential invader or pathogen. However, at the same time the intestinal mucosa has to be permeable to allow the nutrients from [our] food to pass the intestinal barrier. Hence the gut barrier has a complex task: to protect and hinder translocation of harmful intruders but still be permeable to allow uptake of nutrients.

Can you explain the latest thinking on how IBS arises?

Due to what we know so far about IBS, it’s probably multi-factorial: it’s not just one factor or one unifying mechanism driving symptoms in all IBS patients. There are most likely several subgroups of IBS patients where certain mechanisms may be of more importance for symptom generation. Thus, there might be subgroups of IBS patients where immunity, gut microbiota or psychobiology, respectively, is more important for the underlying mechanisms of the disorder.

Today IBS patients are subgrouped according to dominating bowel habit symptoms, which may not at all reflect the mechanisms of the disease. The difficulty in defining “mechanistic” subgroups suggests that underlying disease mechanisms are multi-factorial, and may differ between patient subgroups.

How is the gut-brain axis implicated in IBS?

Recent mouse studies indicate that changes in the gut microbiota could have an important effect on the CNS [central nervous system], as demonstrated by changes in behavior. For obvious reasons it’s more difficult to do these kinds of studies in humans. Still, these mouse studies are really interesting and intriguing in the context of IBS. It is well known that feeling anxious, for example about giving a presentation, will [affect] your gut. Hence there is bidirectional communication between the brain and the gut and how that is of importance in IBS will be in focus of research during the forthcoming years.

What are the clinical implications of studying the mechanisms of IBS?

An improved understanding of the mechanism of a disorder/disease will allow development of better treatment. Due to the fact that IBS is most likely a multifactorial disorder with a heterogeneous patient group it will not be possible to identify “one treatment” for all IBS patients. Hopefully, several different treatment targets will be identified that could be useful for treatment of different subgroups of individuals.

Reference:

Öhman L, Törnblom H & Simrén M. (2014) Crosstalk at the mucosal border: Importance of the gut microenvironment in IBS. Nature Reviews Gastroenterology & Hepatology, doi:10.1038/nrgastro.2014.200

GMFH Editing Team
GMFH Editing Team