# Host-Microbiota-Diet Interactions in Metabolic Syndrome and IBD

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2021 · $521,900

## Abstract

Humanity is increasingly afflicted by chronic inflammatory diseases, including inflammatory bowel disease
(IBD) and metabolic syndrome (Met Syn), which collectively refers to the constellation of metabolic problems
associated with obesity. The grant this application seeks to renew has developed our hypothesis that IBD and
Met Syn share commonalities of disease pathophysiology, namely that poor management of gut microbiota
plays a key role in driving inflammation that is central to both disease states. A central feature of the
microbiota dysbiosis observed in both IBD and Met Syn is a more “aggressive” microbiota that encroaches
upon the gut epithelium, which is likely germane to its promotion of inflammation. One means of inducing
microbiota encroachment and its inflammatory consequences is via consumption of a diet lacking fermentable
fiber. We found that such low fiber diet-induced encroachment involves ablation of microbiota-mediated
innate lymphoid cell (ILC) IL-22 production that normally serves to fortify the epithelium. Consequently,
enriching such diets with the fermentable fiber inulin, but not the insoluble/non-fermentable fiber cellulose,
restored IL-22 production, reduced microbiota encroachment, ameliorated low-grade inflammation, and
protected mice from diet-induced Met Syn. However, we’ve also observed that enriching refined diets with
some fermentable fibers also induced some IL-22-independent negative consequences, including exacerbating
experimentally-induced colitis and promoting liver cancer thus highlighting that, at present, we lack the
knowledge to safely engineer health-promoting foods. Hence, our central overall hypothesis is that better
mechanistic understanding of how dietary fiber impacts the host-microbiota relationship will inform efforts to
design diets and/or more safely and effectively engineer foods that promote beneficial intestine-microbiota
interactions, thus ameliorating gut inflammation and its associated disease states, including IBD and Met Syn.
We will investigate this hypothesis via 3 specific aims: Aim 1: Identify means by which nourishing microbiota
with fiber results in ILC-mediated IL-22 production. Aim 2: Define mechanism underlying psyllium’s ability to
protect against metabolic syndrome and colitis. Aim 3: Develop a means of targeted delivery of colonic IL-22
and investigate its ability to restore gut health and ameliorate inflammatory diseases.

## Key facts

- **NIH application ID:** 10077834
- **Project number:** 5R01DK083890-11
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Andrew T Gewirtz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,900
- **Award type:** 5
- **Project period:** 2010-04-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10077834

## Citation

> US National Institutes of Health, RePORTER application 10077834, Host-Microbiota-Diet Interactions in Metabolic Syndrome and IBD (5R01DK083890-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10077834. Licensed CC0.

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