The effects of dynamic glycan foraging in the ecology of the human gut microbiota


CALL: 2013

DOMAIN: BM - Regenerative Medicine in Age-related Diseases





HOST INSTITUTION: University of Luxembourg

KEYWORDS: human gut microbiota; glycan metabolism; gnotobiotic mice; dysbiosis; inflammatory bowel disease (IBD); Bacteroidetes; intestinal mucus layer

START: 2013-09-01



Submitted Abstract

Research question The microbial communities that inhabit the human gastrointestinal tract (GIT) play roles in both health and disease. Although gut microbes supplement human nutrition by degrading complex carbohydrates (glycans) from our diet, a subset of these microorganisms have evolved the ability to degrade glycans in the host mucus layer as alternative nutrients. Our main research hypothesis is that periods of low dietary glycan intake lead to changes in GIT microbiota, which may represent a dysbiotic state. Furthermore, due to lowered concentrations of diet-derived glycans, we hypothesize that specific gastrointestinal microorganisms alter their physiology to degrade glycans constituting the protective intestinal mucus barrier. Degradation of the mucus layer brings them into closer proximity to host cells and, thus, triggers an enhanced host immune response.Project objectivesA major trait of the human gut bacteria is the ability to degrade complex carbohydrates. Changes in the relative proportions of the ~10^3 different species of gut bacteria, termed dysbiosis, have been implicated in several intestinal disorders, including inflammatory bowel disease (IBD) and colon cancer. Little is known about the mechanisms behind dysbiosis; most studies have taken case-control comparative analytical approaches to identify species with altered abundance during disease. However, changes in abundance do not determine if these species initiated disease or are responding to the altered habitat brought about by the disease process. This idea is emphasized by a recent report that identified several individual bacteria that elicit inflammation in a mouse model of IBD without showing altered abundance between healthy and diseased states [1]. Our hypothesis focuses on changes in bacterial glycan degradation as a potential contributor to dysbiosis and therefore represents a novel approach to conceptualizing this process. In order to test this hypothesis, the project objectives may be summarized as follows:• Development of an experimental model composed of a simplified microbiota (13 bacterial species) of fully sequenced human gut bacteria that are introduced into a germ-free mouse host. • Alternation of feeding of glycan-rich and glycan-deficient diets in order to measure the effects of dietary glycan availability on bacterial mucus layer colonization. Overall, we anticipate that prolonged absence of dietary glycans will drive gut bacteria to increased mucus layer colonization and degradation.

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