# The gut microbiome and glyphosate neurotoxicity

> **NIH NIH R03** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $73,661

## Abstract

ABSTRACT
This application addresses a significant gap in neurotoxicology, i.e. the role of gut microbiome. The microbiome
of the human intestinal tract has a profound effect on human health through its key role in a wide range of host-
related functions. Mounting evidence indicates that dysregulated gut microflora contribute significantly to a
variety of human diseases. The fact that the gut microbiome can be readily affected by external factors raises
questions regarding the role of xenobiotics on intestinal microflora. Glyphosate-based herbicides, such as
Roundup, are the most widely used pesticides worldwide. Glyphosate acts on the shikimate pathway in plants
through inhibiting 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), which disrupts the synthesis of
aromatic amino acids, leading to plant death. Since the shikimate pathway does not exist in mammals, it is
generally believed that glyphosate would be safe in humans. However, glyphosate adverse effects, including
neurotoxicity, in mammals has been well documented. Of particular importance, many functionally important gut
bacteria of rodents and humans do have the shikimate pathway, highlighting that glyphosate may perturb the
gut microbiome and associated shikimate pathway to alter the homeostasis of aromatic amino acids, precursors
of monoamine neurotransmitters. Of note, neurobehavioral disorders are often characterized with dysregulated
aromatic amino acids and neurotransmitter pathways. However, the functional interaction between the gut
microbiome and glyphosate exposure, especially at doses relevant to human exposure, is largely unexplored
yet. The objective of this particular application is to define the impact of glyphosate on disturbing the gut
microbiome and the role of glyphosate-disrupted microbiome in provoking neurotoxicity in the host. We will
approach the problems in three stages by first characterizing the changes in the gut microbiome profiles with
16S rRNA sequencing, and then using shotgun metagenomics and metabolomics to map metabolic alterations.
Lastly, we will define how glyphosate-perturbed gut microbiome causatively alters metabolome, shikimate and
relevant pathways, neurotransmitters and neurobehavioral phenotypes via microbiome transplantation. Our
proposed study is significant and represents a new frontier in glyphosate research because we focus on gut
microbiome perturbation as a novel mechanism of its neurotoxicity. At the completion of this project, it is our
expectation that these results will lay a foundation for future studies aiming at expanding our understanding of
glyphosate neurotoxicity and the role of gut microbiome in human diseases caused by exposure to glyphosate,
the most widely and heavily used herbicide in history.

## Key facts

- **NIH application ID:** 10229481
- **Project number:** 5R03ES032067-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kun Lu
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $73,661
- **Award type:** 5
- **Project period:** 2020-08-06 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229481

## Citation

> US National Institutes of Health, RePORTER application 10229481, The gut microbiome and glyphosate neurotoxicity (5R03ES032067-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10229481. Licensed CC0.

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