# Impact of Gut Bacterial Interactions on the Response to Fiber-Based Prebiotics

> **NIH NIH F30** · WASHINGTON UNIVERSITY · 2021 · $50,516

## Abstract

Project Summary/Abstract
 The gut microbiota has been linked to many features of human health, spawning efforts to develop
microbiota-directed therapeutics or prebiotics. Identifying strategies/reagents for safe, efficacious manipulation
of the microbiota is a high priority goal of current precision medicine initiatives. Achieving this goal requires
informative preclinical models to describe the magnitude and mechanism of prebiotics’ effects on gut microbes
and host biology, and to obtain a fundamental understanding of gut community dynamics. Fiber-based foods
have been shown to have beneficial microbially-mediated effects on health. Understanding how dietary fibers
produce these effects is confounded by (i) their compositional complexity (e.g., what are the bioactive
glycans?), (ii) limited knowledge of which bacteria use specific constituent glycans in fiber, and (iii) competition
and cooperation between bacteria over these glycans. I hypothesize that the polysaccharide components
of fibers and gut community membership interact to dictate responses to fiber-based prebiotics.
Knowledge of these interactions, and their underlying mechanisms, will inform development of improved
microbiota-directed therapeutics.
 I plan to test this hypothesis in a series of experimental aims. AIM 1 will identify fiber-dependent
bacterial interactions in a model human gut microbiota composed of sequenced, cultured bacterial strains
installed in gnotobiotic mice. I will systematically omit bacteria from this model community prior to its
introduction into mice fed a representative ‘unhealthy’ low fiber high saturated fat USA diet ± supplementation
with a purified plant-derived dietary fiber. I will analyze the effects of community manipulation/fiber
supplementation on bacterial gene expression and abundance. Using forward genetic screens (whole genome
transposon mutant libraries) and mass spectrometry-based proteomics and metabolomics, I will characterize
the genetic determinants of bacterial fiber responses and the bioactive components of fiber preparations
across informative community contexts. AIM 2 will extend these gnotobiotic/multi-omic studies through a novel
use of CRISPR technology that allows for selective depletion of targeted bacteria from an established
community in a fiber-supplemented diet context. This work will refine our understanding of microbiota function
and how we might drive a community toward stable, beneficial states. I will generate and analyze many
multi-omic datasets while receiving excellent scientific training from leading researchers in human microbiome
science and computational biology. Together, with the stellar clinical mentorship and training provided by
Washington University SOM, this proposal will help me to develop into an independent physician-scientist.

## Key facts

- **NIH application ID:** 10166599
- **Project number:** 5F30DK123838-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Zachary Walter Beller
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $50,516
- **Award type:** 5
- **Project period:** 2020-06-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166599

## Citation

> US National Institutes of Health, RePORTER application 10166599, Impact of Gut Bacterial Interactions on the Response to Fiber-Based Prebiotics (5F30DK123838-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166599. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*