Research discover potential triggers for inflammatory bowel disease

A new study from the University of Michigan discovered a complex interplay between diet, genes, and the gut microbiota that could explain why Inflammatory bowel disease develops.

The study published in the journal Cell Host & Microbe found that a low-fibre diet led to a proliferation of mucin-degrading bacteria—bacteria that thrive by eating the mucus lining of the intestine.

Researchers analyzed the genetic link using mice with identical immune alterations. While some developed intestinal inflammation, its severity varied and worsened with specific bacteria and a low-fibre diet. Manipulating the presence of a human gut microbiome and dietary fibre in mice models allowed the team to regulate inflammation levels. Moreover, inflammation from fibre-free diets intensified with higher levels of mucin-degrading bacteria.

“These bacteria start foraging on the mucus layer for nutrients, reducing its thickness and barrier function and bringing microbes just 10-100 microns closer to the host tissue. That was enough in the context of the mice with IBD genetics to make them sick,” said Martens, professor of microbiology and immunology at U-M Medical School.

Conversely, feeding the mice a fibre-rich diet prevented inflammation from developing and even returning mice fed low fibre to a high-fibre diet led to a peak in inflammation followed by a decline, suggesting fibre can reverse the deleterious effects of mucus erosion on inflammation.

IBD, particularly in children, is frequently managed with exclusive enteral nutrition (EEN), a fiber-lacking formula-based diet. Surprisingly, EEN reduces inflammation without a clear explanation. To understand, researchers administered dried-down formula to mice with IBD genetics. Results showed varying inflammation levels among the mice, with some experiencing notably less inflammation compared to those on a fibre-free diet, despite EEN also reducing mucus thickness.

The team then discovered that elevated amounts of a single branched-chain fatty acid, isobutyrate, was elevated in EEN fed mice and might suppress inflammation. Isobutyrate is produced through fermentation by some bacteria in the gut.

"Our findings suggest a potential new path for treating IBD. By tailoring specific dietary interventions to influence gut microbiome function, we may be able to manipulate these bacterial communities to alleviate inflammation,” said Gabriel Pereira, first author of the study.

Reference: Gabriel Vasconcelos Pereira, Marie Boudaud, Mathis Wolter, Celeste Alexander, Alessandro De Sciscio, Erica T. Grant, Bruno Caetano Trindade, Eric C. Martens; Opposing diet, microbiome, and metabolite mechanisms regulate inflammatory bowel disease in a genetically susceptible host; Journal: Cell Host & Microbe; DOI: 10.1016/j.chom.2024.03.001