# Impact of gut microbiota-derived molecules on mammalian host health and longevity

> **NIH NIH F32** · STANFORD UNIVERSITY · 2021 · $2,500

## Abstract

Project Summary/Abstract
 My overarching goal is to understand the mechanism by which prominent members of the
human microbiota modulate host aging and age-associated health decline. The human intestinal tract is
inhabited by trillions of microorganisms, collectively referred to as the microbiota, which contributes to
gastrointestinal health and systemic immunity. While metagenomic sequencing has revealed age-associated
compositional changes in the gut microbiota, how individual bacterial species of the human microbiota
functionally contribute to host aging physiology remain largely unexplored. Recent studies have uncovered a
small number of gut microbiota-derived molecules that can bind to cell-surface and nuclear receptors in host
cells and extend lifespan in model organisms, unraveling the potential of microbiota-dependent molecules to
impact human health. However, the human microbiota produces molecules that are vast in numbers and
chemically diverse, posing a tremendous challenge for the field of microbiome science to systematically and
accurately identify them. To overcome this challenge, I built a comprehensive chemical reference library and a
mass spectrometry-based metabolomics pipeline, which enables rapid and high-throughput identification of
over 1000+ metabolites in diverse host samples. My metabolomics profiling of 100+ individual prominent
human gut species and of gnotobiotic mice colonized with individual model gut microbes uncovered a panel of
high abundance, conserved gut microbe-derived molecules. These candidates are tantalizing candidates for
modulating host physiology. Spermidine, one candidate from the polyamine pathway, has been shown to
extend healthspan and lifespan in mammals. However, the role of gut microbe-dependent polyamine
biosynthetic pathway in modulating host aging has not been investigated. Furthermore, the interactions
between the remaining candidates and conserved longevity pathways in the host are largely unknown.
 The goal of my proposal is to investigate the molecular mechanisms by which microbiota-derived
molecules regulate mammalian host health and longevity. Specifically, I hypothesize that a subset of these
candidate molecules impact aspects of host physiology via regulating gastrointestinal health and
systemic aging. My experiment will use genetic manipulations of model gut microbes such as Bt in the
gnotobiotic mouse experimental system to study the impact of microbiota-derived molecules on host aging
biology. Using a combination of mass spectrometry, metabolomics, and microbial genetics, this project will i)
investigate the role of gut microbiota-dependent polyamine biosynthesis in regulating age-associated decline in
host gastrointestinal function, and ii) Identify high-abundance, gut microbiota-derived small molecules that
impact host intestinal health and organismal longevity. This study will provide new insights into the mechanistic
relationships between gut microbiota, small bioactive molecule...

## Key facts

- **NIH application ID:** 10459640
- **Project number:** 3F32AG062119-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Shuo Han
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,500
- **Award type:** 3
- **Project period:** 2019-08-17 → 2022-08-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459640

## Citation

> US National Institutes of Health, RePORTER application 10459640, Impact of gut microbiota-derived molecules on mammalian host health and longevity (3F32AG062119-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10459640. Licensed CC0.

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