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A systematic analysis of metabolic pathways in the human gut microbiota

View ORCID ProfileVictòria Pascal Andreu, View ORCID ProfileHannah E. Augustijn, View ORCID ProfileLianmin Chen, View ORCID ProfileAlexandra Zhernakova, View ORCID ProfileJingyuan Fu, View ORCID ProfileMichael A. Fischbach, View ORCID ProfileDylan Dodd, View ORCID ProfileMarnix H. Medema
doi: https://doi.org/10.1101/2021.02.25.432841
Victòria Pascal Andreu
1Bioinformatics Group, Wageningen University, Wageningen, The Netherlands
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Hannah E. Augustijn
1Bioinformatics Group, Wageningen University, Wageningen, The Netherlands
2University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
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Lianmin Chen
2University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
3University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands
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Alexandra Zhernakova
2University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
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Jingyuan Fu
2University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, Netherlands
3University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, Netherlands
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Michael A. Fischbach
4Department of Bioengineering, Stanford University, Stanford, USA
5Department of Microbiology & Immunology, Stanford University, Stanford, USA
7Chan Zuckerberg Biohub, San Francisco, CA USA
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  • For correspondence: ddodd2@stanford.edu fischbach@fischbachgroup.org marnix.medema@wur.nl
Dylan Dodd
5Department of Microbiology & Immunology, Stanford University, Stanford, USA
6Department of Pathology, Stanford University, Stanford, USA
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  • For correspondence: ddodd2@stanford.edu fischbach@fischbachgroup.org marnix.medema@wur.nl
Marnix H. Medema
1Bioinformatics Group, Wageningen University, Wageningen, The Netherlands
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  • For correspondence: ddodd2@stanford.edu fischbach@fischbachgroup.org marnix.medema@wur.nl
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Abstract

The gut microbiota produce hundreds of small molecules, many of which modulate host physiology. Although efforts have been made to identify biosynthetic genes for secondary metabolites, the chemical output of the gut microbiome consists predominantly of primary metabolites. Here, we systematically profile primary metabolic genes from the gut microbiome, identifying 19,885 gene clusters in 4,240 high-quality microbial genomes. We find marked differences in pathway distribution among phyla, reflecting distinct strategies for energy capture. These data explain taxonomic differences in short-chain fatty acid production and suggest a characteristic metabolic niche for each taxon. Analysis of 1,135 subjects from a Dutch population-based cohort shows that the level of 14 microbiome-derived metabolites in plasma is almost completely uncorrelated with the metagenomic abundance of the corresponding biosynthetic genes, revealing a crucial role for pathway-specific gene regulation and metabolite flux. This work is a starting point for understanding differences in how bacterial taxa contribute to the chemistry of the microbiome.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 26, 2021.
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A systematic analysis of metabolic pathways in the human gut microbiota
Victòria Pascal Andreu, Hannah E. Augustijn, Lianmin Chen, Alexandra Zhernakova, Jingyuan Fu, Michael A. Fischbach, Dylan Dodd, Marnix H. Medema
bioRxiv 2021.02.25.432841; doi: https://doi.org/10.1101/2021.02.25.432841
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A systematic analysis of metabolic pathways in the human gut microbiota
Victòria Pascal Andreu, Hannah E. Augustijn, Lianmin Chen, Alexandra Zhernakova, Jingyuan Fu, Michael A. Fischbach, Dylan Dodd, Marnix H. Medema
bioRxiv 2021.02.25.432841; doi: https://doi.org/10.1101/2021.02.25.432841

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