Effects of Glyphosate and Glyphosate‐Based Herbicides on the Mammalian Gut Microbiome: A Critical Review

ABSTRACT Glyphosate has long been considered to pose negligible direct risk to mammals on the grounds that its molecular target, 5‐enolpyruvylshikimate‐3‐phosphate synthase (EPSPS), of the shikimate pathway, is absent from animal cells. This rationale is inaccurate as a complete toxicological argument, because the shikimate pathway is present in some commensal bacteria in the mammalian gut. This review appraises the evidence that glyphosate and glyphosate‐based herbicides (GBHs) perturb the gut microbiome of mammals. Controlled rodent studies provide the most consistent evidence, with several reporting shifts in community composition, including a depletion of lactobacilli, sometimes accompanied by intestinal inflammation, altered microbial metabolism and increased intestinal permeability. Experimental evidence indicates that luminal aromatic amino acid availability attenuates the antibacterial effect. Formulated products are frequently more disruptive than the active ingredient alone. Some studies suggest that the gut mycobiome is also affected. Neurobehavioural and reproductive outcomes have also been reported, although microbiome‐mediated causality is not established in most studies. Glyphosate‐induced effects are strongly influenced by dose, by whether the active ingredient or a formulated product is tested, by sex and by a developmental window of exposure. Available human data, confined to in vitro systems and small biomonitoring cohorts, are limited. In conclusion, glyphosate and some GBHs can perturb the rodent gut microbiome under defined experimental conditions. These animal findings are relevant to hazard assessment and support inclusion of microbiome endpoints in regulatory toxicology, although the magnitude and health relevance of comparable effects at realistic human exposures remain uncertain.