# Low dietary fiber and gut microbiota-induced mucus layer erosion as IBD triggers

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $542,873

## Abstract

Summary
The precise etiologies of the multiple disorders collectively known as inflammatory bowel disease (IBD) remain
unknown. Despite identification of >100 human genetic polymorphisms that are thought to play a role, an
unexplained facet of genetic predisposition to IBD is that it typically explains only a fraction of disease risk. The
existence of modifying factors has thus been invoked to explain the weakly penetrant disease development.
Environmental factors—including diet and the dense community of gut microbes (microbiota)—have been
prominent suspects. However, the functional interconnections between these potential contributors remain
unknown. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut
microbiota composed of fully sequenced and metabolically characterized commensal bacteria, we have begun
to elucidate the mechanistic interactions between dietary fiber, the gut microbiota and the colonic mucus
barrier, which serves as a primary defense against encroachment by intestinal bacteria. During dietary fiber
deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to
erosion of the mucus layer. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota,
promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. More
strikingly, when this same synthetic microbiota is assembled in mice deficient in interleukin 10 (IL-10), a
cytokine for which loss of function defects have been associated with human IBD, animals develop lethal
spontaneous inflammation in the absence of C. rodentium, but only on a low fiber diet. Our work has therefore
revealed functional interconnections between diet, gut microbiota, mucosal barrier function and spontaneous
IBD development. Our central hypothesis is that there is a dynamic balance between fiber- and mucus-
degrading bacteria, such that in low fiber conditions the mucus layer is increasingly eroded resulting in a
temporal disease progression involving host or microbial changes and that this can be ameliorated by
preventative or therapeutic fiber consumption. The proposed work will extend the findings outlined above by
first measuring the respective contributions of mucin-degrading bacteria and their functions towards eroding
the mucosal barrier and precipitating inflammation. Following this, we will measure the impact of different types
of dietary fibers, along with their dosing and consumption schedules, that are required to treat or prevent
inflammation. Finally, we will perform time course experiments with microbial, immunological and mucosal
barrier readouts to determine how disease progression in this model—which occurs over the course of several
weeks—is driven by changes in the homeostasis between gut microbes and the host. We anticipate that our
findings will provide detailed functional insight into the constellation of genetic and environmental ...

## Key facts

- **NIH application ID:** 9900776
- **Project number:** 5R01DK118024-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Eric C Martens
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $542,873
- **Award type:** 5
- **Project period:** 2018-07-03 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900776

## Citation

> US National Institutes of Health, RePORTER application 9900776, Low dietary fiber and gut microbiota-induced mucus layer erosion as IBD triggers (5R01DK118024-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9900776. Licensed CC0.

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