A fiber-deprived diet may degrade the colonic mucus barrier and promote enteric pathogen infection in mice

Dietary fiber from plant-based foods is the most common fuel for some bacterial species in the gut microbiota and in some contexts has been shown to play a key role in protecting the host against immune-mediated diseases such food allergies and even neurological disorders. A diet rich in microbiota-accessible carbohydrates (MACs), which are complex carbohydrates found in fruits, vegetables, whole grains, and legumes, has a crucial role in shaping the gut microbial ecosystem. In this context, conserving and restoring the human gut microbiome by increasing consumption of dietary fiber is a current nutritional challenge. However, little is known about the underlying mechanisms by which fiber deprivation impacts the gut microbiota and influences disease risk.

A recent study, led by Dr. Eric Martens from the University of Michigan Medical School in Ann Arbor (USA), has found that a fiber-deprived diet may lead to a degradation of the colonic mucus layer and enhance enteric pathogen infection in mice.

The researchers studied interactions between dietary fiber, gut microbiota and the colonic mucus barrier in a gnotobiotic mouse model, in which germ-free mice were colonized with synthetic human gut microbiota with a known full genetic signature that allowed tracking of their activity over time. The 14 selected species were chosen to represent the five dominant phyla and collectively hold a versatile capacity for degrading indigestible polysaccharides.

Three groups of mice were maintained by constant feeding of one of three different diets: fibre-rich (contained intact fiber particles present naturally in food), fiber-free, or prebiotic (contained a mixture of purified polysaccharides, matching those used in prebiotic formulations). To imitate fluctuating exposures to dietary fiber in humans, four other groups were alternated between the fiber-rich and fiber-free or prebiotic and fiber-free diets on a daily or 4-day basis. During either chronic or intermittent dietary fiber deficiency, there was an increase in the proliferation of mucus-degrading species such as Akkermansia muciniphila and Bacteroides caccae and a decrease in fiber-degrading bacteria such as Eubacterium rectale and Bacteroides ovatus both in fecal samples and in the colonic lumen and mucus layer.

The increased abundance of mucin-degrading bacteria was explained by their ability to degrade mucus as an alternative nutrient, as the lack of naturally complex plant fiber (free-fiber and prebiotic diets) led to a higher expression of carbohydrate active enzymes, sulfatases, and proteases that enable gut bacteria to utilize dietary fiber and mucosal polysaccharides.

The colonic mucus layer thickness from proximal colon to rectum was highest in the colonized group fed the fiber-rich diet. Besides this, mucus production was altered in colonized mice fed the fiber-free diet and led to altered host intestinal responses. Fecal lipocalin – a neutrophil protein involved in low-grade inflammation – was increased in the group of colonized mice fed the fiber-free diet compared to those fed the fiber-rich diet. Secondly, colon length was shorter in colonized fiber-free diet mice when compared to colonized fiber-rich fed mice. Altogether, these data show that fiber deprivation led the gut microbiota to degrade the colonic mucus barrier and altered some host responses.

Finally, in order to test whether the reduction in colonic mucus layer thickness was associated with increased pathogen susceptibility, the researchers examined changes in gut microbial communities in response to Citrobacter rodentium, a murine pathogen that resembles the human enteric species Escherichia coli. When mice were infected with C. rodentium, this invading pathogen flourished more in the guts of mice fed a fiber-free diet. Besides this, many of those mice began to show signs of illness and lost weight over time. Measurements of inflamed tissue area in different intestinal segments showed that the colonized fiber-free diet group experienced inflammation that covered significantly more surface area, resulting in more severe colitis by C. rodentium. These results show that a fiber-deprived gut microbiota promotes heightened pathogen susceptibility.

To sum up, a fiber-deprived diet may promote expansion and activity of colonic mucus-degrading bacteria, with a consequently negative impact on the colonic mucus layer and increased susceptibility to a gastrointestinal pathogen through reduction of this barrier.

Reference:

Desai MS, Seekatz AM, Koropatkin NM, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016; 167(5):1339-53. doi: 10.1016/j.cell.2016.10.043.