Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome.
Level 5 - mechanism / opinion, no new human data
In silico bioinformatic analysis and computational modeling of public datasets (Level 5 by design analogy)
PubMed 34345834 · doi:10.1016/j.crtox.2020.04.001
What was done
Authors analyzed public human microbiome datasets to evaluate potential sensitivity to glyphosate via the shikimate pathway. They assessed shikimate pathway abundance and transcriptional activity across 734 paired metagenomes and metatranscriptomes. They also classified 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) homologues into class I (sensitive) or class II (resistant) across 44 microbial subspecies reference genomes representing 72% of assigned microbial abundance in 2,144 human fecal metagenomes, and screened for carbon-phosphorus lyase degradation pathways.
What was found
The shikimate pathway was incomplete in most gut bacteria and mostly transcriptionally inactive across 734 paired metagenomes and metatranscriptomes. Among the 44 predominant subspecies accounting for 72% of total microbial abundance in 2,144 fecal metagenomes, 9 subspecies possessed class II (glyphosate-resistant) EPSPS enzymes. Metagenomic analysis also identified the carbon-phosphorus lyase pathway in certain Proteobacteria, suggesting potential capacity to degrade glyphosate.
Why it matters
Because most human gut bacteria appear to be aromatic amino acid auxotrophs with inactive shikimate pathways, the direct inhibition of gut bacteria by glyphosate via EPSPS blockade may be lower than previously hypothesized.
Limits
Findings rely entirely on in silico computational predictions from public sequencing databases. The study did not measure in vivo or in vitro glyphosate exposure, non-EPSPS toxic mechanisms, metabolic shifts under live physiological conditions, or the effects of commercial herbicide formulations containing adjuvants.
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