# Proanthocyanidin metabolites produced by commensal gut microbes may promote metabolic resilience

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2021 · $385,506

## Abstract

Project Summary: This multidisciplinary proposal aims to define how proanthocyanidins (PACs), a major class
of grape polyphenols (GPs), alter the intestinal milieu to promote a biological signature associated with resilience
to metabolic syndrome (MetS) and type-2 diabetes (T2D). Using urine, blood, and gut microbiota samples from
PAC-supplemented mice and GP-supplemented humans, microbiome-wide association studies will be
performed to correlate changes in bacterial strains/species to increases/decreases in microbial metabolites
(MMs). PAC treatment of bacteria in vitro and of germfree mice inoculated with bacterial isolates or defined
consortia will establish relationships between specific commensal bacteria and PAC-derived MMs, which will
then be tested for bioactivity in mammalian cell culture assays and a high-fat diet (HFD)-induced mono-
associated germfree (GF) model of MetS/T2D. PACs are associated with metabolic resilience; however,
mechanism(s) of systemic protection have remained elusive due to generally poor absorption and uncertainty
about molecular targets. PACs reach the colon where they are biotransformed to MM with greater bioavailability;
however, the specific bacteria responsible for these transformations, the molecular targets of resulting MM, and
validation of their efficacy in preclinical models of MetS/T2D remain to be investigated. We observed that GP
supplementation can induce a bloom in the mucolytic gut bacterium Akkermansia muciniphila in association with
reduced serum lipopolysaccharide, less intestinal and systemic inflammation, increased expression of tight
junction protein occludin, improved glucose metabolism, and less adiposity and weight gain in HFD-fed mice.
Increased abundance of A. muciniphila has been observed after gastric bypass surgery and metformin treatment,
underlining its importance in positive metabolic outcomes. GP-supplemented mice also showed: 1) decreased
bacterial community richness; 2) alterations in genera consistent with improved gut barrier integrity and lactic
acid-production; 3) decreased serum levels of bacterial-derived secondary bile acids; 4) decreased thickness of
the mucus layer adjacent to the intestinal epithelium with redistribution of mucus in the colon; and 5) increased
serum levels of desaminotyrosine (DAT), a PAC-derived MM associated with immune modulation and resilience
against virus-induced inflammation. Finally, we showed that PACs, are sufficient to increase intestinal
abundance of A. muciniphila. Our data suggest PAC-induced alterations of the intestinal milieu promote
metabolic resilience. To establish cause-effect relationships we propose to: 1) correlate urine/blood metabolites
with gut bacterial strains/species using samples collected in longitudinal studies of GP-supplemented humans
and PAC-treated mice with concomitant monitoring of metabolic and histological phenotypes in HFD- and low-
fat diet (LFD)-fed murine hosts; 2) perform in vitro and germfree mouse studies ...

## Key facts

- **NIH application ID:** 10234072
- **Project number:** 5R01AT010242-04
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Diana Elizabeth Roopchand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $385,506
- **Award type:** 5
- **Project period:** 2018-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234072

## Citation

> US National Institutes of Health, RePORTER application 10234072, Proanthocyanidin metabolites produced by commensal gut microbes may promote metabolic resilience (5R01AT010242-04). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10234072. Licensed CC0.

---

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