# Glyphosate impairs glucose homeostasis via gut microbiome induced alterations to bile acid signaling

> **NIH NIH F31** · UNIVERSITY OF ARIZONA · 2024 · $32,431

## Abstract

PROJECT SUMMARY
The prevalence of type 2 diabetes (T2D) is steadily increasing, highlighting a critical need to understand the
etiology of this condition. In line with the dramatic rise in T2D, chronic insecticide and herbicide use has also
increased, with RoundUp being the most applied herbicide in the US. As glyphosate, the active ingredient in
RoundUp, targets the shikimate pathway in found in plants, but not mammals, glyphosate is proposed to be safe
for human use. However, our preliminary data show that, even at a dose equivalent to the US Acceptable Daily
Intake, chronic glyphosate exposure impairs oral glucose tolerance in mice. Unlike mammalian cells, several
species of gut bacteria utilize the shikimate pathway, and data from our lab and others indicates that chronic
glyphosate exposure alters the gut microbiome. It is now well-known that the gut microbiome impacts host health,
mediated at least in part by bacterial modification of host endogenous compounds, including bile acids. Primary
bile acids, produced in the liver, are biotransformed into secondary bile acid species by gut bacteria and act as
signaling molecules involved in glucose homeostasis. My preliminary data shows that chronic glyphosate
exposure in mice is associated with a decrease in secondary bile acids, likely occurring due to gut microbiome
shifts. As secondary bile acids primarily agonize the G-protein coupled bile acid receptor 1 (Gpbar1, also known
as TGR5), and TGR5 activation is beneficial for glucose tolerance, it is plausible that glyphosate-mediated shifts
in the gut microbiome impact glucose homeostasis via modification of bile acids and TGR5 signaling. This
hypothesis will be tested in the following Aims: 1) Determine the impact of glyphosate exposure on glucose
tolerance and the gut microbiome and determine if the gut microbiome is necessary for the effects; 2) Determine
how glyphosate alters enterohepatic bile acid homeostasis and if TGR5 mediates the effects of glyphosate on
glucose tolerance. This fellowship will provide training in transgenic mouse colony maintenance, shotgun
metagenomic sequencing and analyses, and bile acid quantification, as well as opportunities for collaboration
with experienced scientists in the field and professional development through conference attendance and
presentations. The lab of Dr. Frank Duca and the University of Arizona provide an excellent environment for this
research, with access to the Microbiome Core at the Steele Children’s Research Center, the University of Arizona
Gnotobiotic Facility, as well as knowledge from researchers in the fields of pharmacology and toxicology and
metabolism.

## Key facts

- **NIH application ID:** 10873735
- **Project number:** 5F31DK137424-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Rachel Meyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $32,431
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873735

## Citation

> US National Institutes of Health, RePORTER application 10873735, Glyphosate impairs glucose homeostasis via gut microbiome induced alterations to bile acid signaling (5F31DK137424-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10873735. Licensed CC0.

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