# Personalizing prebiotic therapies that target human gut microbiota

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $357,750

## Abstract

Dietary carbohydrates nourish human gut bacterial communities (microbiota) that resist pathogens, metabolize
drugs, and train the immune system. Short-chain fatty acids, which are end products of microbial
polysaccharide fermentation, are also crucial metabolic precursors and energy sources for human colon cells.
The potential health benefits of dietary carbohydrates that stimulate the growth and activity of intestinal
bacteria (prebiotics) have led millions of Americans to consume these compounds annually. Yet, the effects of
prebiotics on gut microbiota and their fermentation are known to vary substantially between individuals. Our
objective here is to understand why and how prebiotics should be tailored to individuals and their gut
microbiota. To address advance prebiotic research, we have developed innovative new tools: a microfluidic
technique for creating and assaying millions of individual bacterial cultures; Bayesian state-space models for
longitudinal microbiota data; and, an artificial human intestine that we can sample and manipulate with arbitrary
frequency. We propose combining these new methods to test our central hypothesis that the impact of
prebiotic treatments can be maximized by personalization to individuals and their microbiota. Our proposal has
three specific aims: 1) Use our microfluidic culture techniques to measure how different carbohydrate
compounds affect the growth and metabolism of thousands of distinct human gut bacterial species. By
identifying which bacterial species are directly stimulated by prebiotics, we can begin to understand how these
treatments reshape each individuals' gut microbiota. 2) Develop a probabilistic state-space model of microbial
community dynamics and apply it our existing datasets tracking human diet, gut microbiota, and short chain
fatty acid levels over time. The resulting model will pinpoint interactions between bacterial species growth,
microbial fermentation, and subject diet that influence response to prebiotic treatments. 3) Use our artificial
human gut models to carry out prebiotic trials on human gut microbiota with doses that are either fixed or
periodically updated based on changes to microbiota structure and function. The resulting data will establish
how initial microbiota shifts caused by prebiotic treatment affect later dose responses, as well as assess
whether eliminating differences in host compliance and response affect variations in prebiotic impact.
Ultimately, the proposed aims are expected to provide the first systematic study on the underlying mechanisms
driving individualized responses to prebiotic treatments and help establish a new research field focused on
personalized prebiotic treatments. The computational and experimental techniques developed here will also
serve as a preclinical platform that could directly translate potential prebiotics to human clinical trials. More
broadly, these techniques are designed to be generalizable and could thus be used for the rati...

## Key facts

- **NIH application ID:** 10065002
- **Project number:** 5R01DK116187-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Lawrence Anthony David
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $357,750
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10065002

## Citation

> US National Institutes of Health, RePORTER application 10065002, Personalizing prebiotic therapies that target human gut microbiota (5R01DK116187-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10065002. Licensed CC0.

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