Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome

The herbicide active ingredient glyphosate can affect the growth of microorganisms, which rely on the shikimate pathway for aromatic amino acid biosynthesis. However, it is uncertain whether glyphosate exposure could lead to perturbations in the population of human gut microbiota. We have addressed...

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Main Authors: Robin Mesnage, Michael N. Antoniou
Format: Article
Language:English
Published: Elsevier 2020-06-01
Series:Current Research in Toxicology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666027X20300049
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author Robin Mesnage
Michael N. Antoniou
author_facet Robin Mesnage
Michael N. Antoniou
author_sort Robin Mesnage
collection DOAJ
description The herbicide active ingredient glyphosate can affect the growth of microorganisms, which rely on the shikimate pathway for aromatic amino acid biosynthesis. However, it is uncertain whether glyphosate exposure could lead to perturbations in the population of human gut microbiota. We have addressed this knowledge gap by analysing publicly available datasets to provide new insights into possible effects of glyphosate on the human gut microbiome. Comparison of the abundance of the shikimate pathway in 734 paired metagenomes and metatranscriptomes indicated that most gut bacteria do not possess a complete shikimate pathway, and that this pathway is mostly transcriptionally inactive in the human gut microbiome. This suggests that gut bacteria are mostly aromatic amino acid auxotrophs and thus relatively resistant to a potential growth inhibition by glyphosate. As glyphosate blocking of the shikimate pathway is via inhibition of EPSPS, we classified E. coli EPSPS enzyme 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 2144 human faecal metagenomes, 9 subspecies have class II EPSPS. The study of publicly available gut metagenomes also indicated that glyphosate might be degraded by some 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 gut microbiome. Further investigations using more advanced molecular profiling techniques are needed to ascertain whether glyphosate and glyphosate-based herbicides can alter the function of the gut microbiome with consequent health implications.
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spelling doaj.art-865843b955ce406bb05b274e3fdbb0e32022-12-21T22:42:10ZengElsevierCurrent Research in Toxicology2666-027X2020-06-0112533Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiomeRobin Mesnage0Michael N. Antoniou1Corresponding author.; Gene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, 8th Floor, Tower Wing, Great Maze Pond, London SE1 9RT, United KingdomGene Expression and Therapy Group, King's College London, Faculty of Life Sciences & Medicine, Department of Medical and Molecular Genetics, Guy's Hospital, 8th Floor, Tower Wing, Great Maze Pond, London SE1 9RT, United KingdomThe herbicide active ingredient glyphosate can affect the growth of microorganisms, which rely on the shikimate pathway for aromatic amino acid biosynthesis. However, it is uncertain whether glyphosate exposure could lead to perturbations in the population of human gut microbiota. We have addressed this knowledge gap by analysing publicly available datasets to provide new insights into possible effects of glyphosate on the human gut microbiome. Comparison of the abundance of the shikimate pathway in 734 paired metagenomes and metatranscriptomes indicated that most gut bacteria do not possess a complete shikimate pathway, and that this pathway is mostly transcriptionally inactive in the human gut microbiome. This suggests that gut bacteria are mostly aromatic amino acid auxotrophs and thus relatively resistant to a potential growth inhibition by glyphosate. As glyphosate blocking of the shikimate pathway is via inhibition of EPSPS, we classified E. coli EPSPS enzyme 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 2144 human faecal metagenomes, 9 subspecies have class II EPSPS. The study of publicly available gut metagenomes also indicated that glyphosate might be degraded by some 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 gut microbiome. Further investigations using more advanced molecular profiling techniques are needed to ascertain whether glyphosate and glyphosate-based herbicides can alter the function of the gut microbiome with consequent health implications.http://www.sciencedirect.com/science/article/pii/S2666027X20300049GlyphosateGut microbiomeMetagenomePesticidesShikimate
spellingShingle Robin Mesnage
Michael N. Antoniou
Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
Current Research in Toxicology
Glyphosate
Gut microbiome
Metagenome
Pesticides
Shikimate
title Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
title_full Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
title_fullStr Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
title_full_unstemmed Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
title_short Computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
title_sort computational modelling provides insight into the effects of glyphosate on the shikimate pathway in the human gut microbiome
topic Glyphosate
Gut microbiome
Metagenome
Pesticides
Shikimate
url http://www.sciencedirect.com/science/article/pii/S2666027X20300049
work_keys_str_mv AT robinmesnage computationalmodellingprovidesinsightintotheeffectsofglyphosateontheshikimatepathwayinthehumangutmicrobiome
AT michaelnantoniou computationalmodellingprovidesinsightintotheeffectsofglyphosateontheshikimatepathwayinthehumangutmicrobiome