Emerging evidence is showing that a one-size-fits-all treatment for irritable bowel syndrome (IBS) may not be feasible. That is mainly due to the complex etiology of IBS, with multiple environmental triggers leading to gastrointestinal symptoms and impaired quality of life.

Diet is one of the major culprits of the symptoms reported by patients. For instance, gastrointestinal symptoms related to food are reported by 84% of patients with IBS, and are especially true for foods containing incompletely absorbed carbohydrates and fat.

Studies in mice and humans have revealed several mechanisms by which food may result in IBS symptoms. Mechanisms subject to the largest number of studies include, among others, the direct osmotic effects of food in the gut lumen, changes to the gut microbiota and immune activation.

Indeed, randomized controlled trials (RCTs) suggest that gluten-free diets and diets low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may improve IBS symptoms in certain patients through the above-mentioned mechanisms.

Other approaches, such as excluding foods for which we have developed immunoglobulin G antibodies, limiting dietary fiber intake, low-fructose/fructan diets and low carbohydrate diets, are all based on clinical experience, but have not always been formally tested in clinical trials.

Beyond the plausibility of different mechanisms, it is also important to assess exclusion diets’ efficacy and safety in patients with IBS through the use of RCTs. And the major challenges being faced by researchers and clinicians in that regard are discussed in a recent review article in Nature Reviews Gastroenterology & Hepatology.

The challenges include the design of the control diet, which can be participants’ regular diet; an alternative or sham diet; an inverse diet; or a diet with offending foods. None of those options is free from disadvantages, while blinding is also a limitation. It is suggested that the intervention diet participants are following, should not be advertised until it is proved to reduce symptoms.

In addition to considering the choice of the control group, collecting mechanistic and symptom data is also relevant for elucidating mechanisms by which exclusion diets might be effective in IBS. How wheat might cause IBS symptoms has been widely studied in nutrition and microbiome studies. However, gluten alone is not the major culprit of IBS symptoms; rather, FODMAPs (e.g. fructans), alpha-amylase trypsin inhibitors (ATIs) and wheat-germ agglutinin are also involved, possibly through innate immune responses.

Elena Verdu’s lab has shown that Pseudomonas in the small intestine produce elastases that have proteolytic activity against gluten. However, in the presence of genes associated with celiac disease, they can also synergize with gluten and induce inflammatory responses. Likewise, wheat ATIs can synergize with gluten and induce an innate immune system activation by activating the Toll-like receptor 4 pathway, leading to increased intestinal permeability, cholinergic activation and gut dysmotility. The observation that Lactobacillus can degrade ATIs, leading to a reduction in its pro-inflammatory effects, opens up the potential of using probiotics in celiac disease and in wheat sensitivity in IBS patients.

On the whole, the mechanisms by which food drives IBS symptoms are becoming progressively clear. It seems that taking those mechanisms, coupled with clinical data, into account offers valuable insights into the nutritional management of IBS and other functional gastrointestinal disorders, especially in the context of studies that clarify the contribution of both the gut microbiota and the immune system in response to exclusion diets.



Böhn L, Störsrud S, Törnblom H, et al. Self-reported food-related gastrointestinal symptoms in IBS are common and associated with more severe symptoms and reduced quality of life. Am J Gastroenterol. 2013; 108(5):634-41. doi: 10.1038/ajg.2013.015.

Moayyedi P, Simrén M, Bercik P. Evidence-based and mechanistic insights into exclusion diets for IBS. Nat Rev Gastroenterol Hepatol. 2020; 17:406-13. doi: 10.1038/s41575-020-0270-3.