Can glyphosate and commercial glyphosate-based herbicide formulations alter human microbiomes?

Abstract

Glyphosate exerts its herbicidal action by inhibiting 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) of the shikimate pathway, thus blocking aromatic amino acid biosynthesis. Glyphosate may also affect shikimate pathway positive microorganisms and is patented as an antibiotic. We have recently shown that glyphosate and a commercial formulation of glyphosate-based herbicide can indeed inhibit EPSPS and the shikimate pathway in the gut microbiome of rats. However, it is uncertain whether glyphosate exposure could lead to perturbations of human microbiota including those of the gut. We have thus conducted bioinformatics analyses of publicly available datasets for effects of glyphosate on human microbiomes, especially the gut. Data from the Human Microbiome Project for 6 major body sites shows that the shikimate pathway is found in almost all individuals and all locations. Comparison of the abundance of the shikimate pathway in paired metagenomes and metatranscriptomes indicated that in the human gut microbiome most bacteria do not possess a complete shikimate pathway, which is mostly transcriptionally inactive. This suggests that gut bacteria are mostly aromatic amino acid auxotrophs and thus relatively resistant to potential growth inhibition by glyphosate. We also classified E. coli EPSPS homologues as Class I (sensitive to glyphosate) and Class II (resistant to glyphosate). Among 44 subspecies reference genomes, accounting for 72% of the total assigned microbial abundance in 2,144 human faecal metagenomes, 9 subspecies have Class II EPSPS. The study of gut metagenomes also indicated that glyphosate might be degraded by Proteobacteria in the human gut microbiome using the carbon-phosphorus lyase pathway. Overall, there is limited experimental evidence available for the effects of glyphosate on the human microbiomes including the gut. Further investigations using more advanced molecular profiling techniques including transcriptomics and metabolomics are needed to ascertain whether glyphosate and glyphosate-based herbicides can alter the function of microbiomes with consequent health implications.