Mesnage · Environmental health perspectives 2021 · Controlled animal exposure study with in vitro assays · n=?

Use of Shotgun Metagenomics and Metabolomics to Evaluate the Impact of Glyphosate or Roundup MON 52276 on the Gut Microbiota and Serum Metabolome of Sprague-Dawley Rats.

Cited 151 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Animal study (rodent toxicity model) and in vitro assay.

PubMed 33502259 · doi:10.1289/EHP6990 · record verified 2026-08-29

What was done

Sprague-Dawley rats were exposed for 90 days to glyphosate (0.5, 50, or 175 mg/kg body weight/day) or the herbicide formulation Roundup MON 52276 at equivalent glyphosate doses. Researchers evaluated gut effects using cecal microbiome shotgun metagenomics along with cecal and serum metabolomics. Supplementary in vitro growth assays were conducted on Lacticaseibacillus rhamnosus strains exposed to glyphosate, MON 52276, and Roundup GT plus.

What was found

Glyphosate and MON 52276 exposure led to cecal accumulation of shikimic acid and 3-dehydroshikimic acid, consistent with inhibition of the microbial shikimate pathway enzyme 5-enolpyruvylshikimate-3-phosphate synthase. Cecal levels of cysteinylglycine, γ-glutamylglutamine, and valylglycine increased, though these changes were not reflected in serum. Serum metabolomics demonstrated alterations in nicotinamide, branched-chain amino acid, methionine, cysteine, and taurine pathways, indicating oxidative stress, with more pronounced changes from MON 52276 than glyphosate alone. Metagenomics revealed increased abundance of Eggerthella spp., Shinella zoogleoides (MON 52276 only), Acinetobacter johnsonii, and Akkermansia muciniphila. In vitro, Roundup GT plus inhibited bacterial growth at concentrations where glyphosate and MON 52276 showed no effect. Numerical values and effect sizes were not provided in the abstract.

Why it matters

This study provides evidence that glyphosate-based herbicides can directly inhibit the shikimate pathway of the mammalian gut microbiome in vivo and alter host metabolic profiles.

Limits

The study was conducted in a rodent model and bacterial cultures, which may not directly reflect human physiological or microbiome responses. The abstract does not report the total sample size (n), baseline microbiome controls, or quantitative effect sizes and statistical confidence intervals.

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