# Characterization of Microbiota-derived Polymethoxyflavone Metabolites and their Anti-inflammatory Actions in the Colon

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2020 · $382,120

## Abstract

PROJECT SUMMARY
 Accumulating evidence suggested that gut microbiota-derived metabolites of dietary flavonoids are
important for their biological actions in the colon such as anti-inflammation. However, currently, there is only
a poor understanding of the formation and biofunctions of microbiota-derived flavonoid metabolites, which
greatly limits our ability to develop dietary flavonoid-based strategies for inhibiting colonic inflammation.
Consumption of citrus fruits and their components has been found to associate inversely with inflammation-
related chronic diseases in humans. Polymethoxyflavones (PMFs), a unique class of citrus flavonoids,
displayed potent anti-inflammatory properties in the colon in our animal studies. We found that gut
microbiota mediated the production of an array of colonic metabolites of PMFs after their oral administration
in mice, and these metabolites possessed much stronger anti-inflammatory effects than their parental
PMFs. Importantly, our results showed that oral intake of PMFs by human volunteers resulted in the
production of these bioactive metabolites in human stool. Furthermore, we identified multiple strains of
PMF-metabolizing bacteria from human stool and found that dietary PMFs modulated the abundance and
metabolic functions of these bacteria in mice with colitis. Overall, our results provided a strong basis for the
application of citrus PMFs in the prevention of colonic inflammation and associated diseases. The objective
of this project is to elucidate the mode of interaction between PMFs and gut microbiota, and its implication
in inhibiting colonic inflammation. Based on our preliminary results, we hypothesize that gut microbiota
mediates the production of bioactive PMF metabolites, and these metabolites are critical for the anti-
inflammatory actions of PMFs in the colon. To test our hypothesis, we will pursue the following 3 specific
aims: 1) Identify novel microbiota-derived metabolites of PMFs in the colon and characterize their tissue
profiles in PMF-fed mice; 2) Determine the role of microbiota-derived PMF metabolites in inhibiting colonic
inflammation; and 3) Characterize the interaction between PMFs and PMF-metabolizing fecal bacteria in
both healthy mice and mice with colitis. Our rationale is that the successful completion of this project will
contribute to the development of effective dietary strategies for amelioration of colonic inflammation and
associated diseases through the PMF/microbiota interaction.

## Key facts

- **NIH application ID:** 10018668
- **Project number:** 5R01AT010229-03
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** Hang Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,120
- **Award type:** 5
- **Project period:** 2018-09-20 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018668

## Citation

> US National Institutes of Health, RePORTER application 10018668, Characterization of Microbiota-derived Polymethoxyflavone Metabolites and their Anti-inflammatory Actions in the Colon (5R01AT010229-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10018668. Licensed CC0.

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