A human gut microbiota deprived of dietary fibre compensates the lack of nutrients by degrading the mucus barrier that lines the intestinal wall, thus increasing the risk of pathogen infection. The study containing these findings, conducted by LIH researcher Dr Mahesh Desai together with national and international teams of researchers, was published in the November 2016 issue of the prestigious journal Cell.

Human dietary habits used to include a large amount of fibres (up to 100 g per day) that have proven health benefits. Over the last few decades, this intake has fallen drastically mainly due to the consumption of processed food and a change in our lifestyles which has been connected to increased cases of intestinal diseases including colon cancer. However, the mechanisms behind these connections had remained poorly understood.

Fibre-deprived diet makes friendly gut microbes furious
The researchers aimed to investigate the impact of a high-fibre and a fibre-deprived diet on the gut microbiota composition and physiology, and the resulting effects on the colonic mucus barrier. For this, they selected 14 representative, well-characterised bacterial species from the human gut to colonise the intestine of germ-free mice and observed that this synthetic microbiome was able to respond dynamically to variations in dietary fibre intake.

Mucus-degrading bacteria were significantly enriched in the absence of dietary fibre, leading to increased production of mucus-degrading bacterial enzymes. ‘We have found a mechanism by which reduced consumption of dietary fibre makes some of our friendly intestinal bacteria furious’, says Dr Desai, group leader at LIH’s Department of Infection and Immunity and lead author on the publication.

Furious gut microbes befriend enteric pathogens
By analysing histological sections of the gut, the scientists revealed that fibre deprivation leads the microbiota to degrade the colonic mucus barrier to reduce its integrity. As the mucus lining of the gut is an important innate barrier to pathogen invasion, the authors rationalised that fibre-deprived mice would be more susceptible to infection.

To better understand the functional implications of the reduced mucus barrier, the researchers infected the thick and thin mucus layer phenotypes of mice with the murine pathogen Citrobacter rodentium − this enteric pathogen easily traversed the mucus layer to reach the epithelium and caused severe disease in mice fed with fibre-free diet. ‘The “holes” created by the microbiota while eroding the mucus serve as wide open doors for pathogenic microorganisms to invade’, explains Dr Desai.

Implications for health and dietary therapeutics
The findings of this study highlight the important role of fibre in nutrition and reveal a strong link between diet, gut microbiota and a healthy intestinal barrier. ‘Our results amplify everything that doctors and nutritionists have been telling us for decades: eat a lot of fibre from diverse natural sources,’ emphasises Dr Eric Martens, Associate Professor at the University of Michigan Medical School, who conceived, designed and led the study together with Dr Desai.

The researchers also tried a diet excluding fruits and vegetables but integrating classical prebiotic supplementation. This diet resulted in a similar erosion of the mucus layer as observed in the lack of fiber. ‘These exciting results open up avenues for designing next-generation prebiotics using dietary therapeutics that would target human gut microbiome and might be useful in treating and preventing diseases of the intestinal tract such as inflammatory bowel disease’, says Prof Markus Ollert, Director of LIH's Department of Infection and Immunity.

An international team with inter-disciplinary expertise
The outcomes of the research result from a collaboration under the lead of LIH’s Department of Infection and Immunity together with LIH's Department of Oncology, the Luxembourg Centre for Systems Biomedicine of the University of Luxembourg, the University of Michigan Medical School (Ann Arbor, US), the Washington University School of Medicine (St-Louis, US), and the Aix-Marseille University (Marseille, France). The study was primarily supported by the Luxembourg National Research Fund (FNR) (INTER Mobility and CORE grants) as well as the National Institutes of Health (R01 grant).

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Desai et al., 2016, Cell 167, 1339–1353
DOI :  http://dx.doi.org/10.1016/j.cell.2016.10.043