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<p>Disruption of hydrogen (H<sub>2</sub>) cycling in the gut is linked to gastrointestinal disorders, infections and cancers. However, the mechanisms and microorganisms controlling H<sub>2</sub> production in the gut remain unresolved. Here we show that gut H<sub>2</sub> production is primarily driven by the microbial group B [FeFe]-hydrogenase. Metagenomics and metatranscriptomics of stool and tissue biopsy samples show that hydrogenase-encoding genes are widely present and transcribed in gut bacteria. Assessment of 19 taxonomically diverse gut isolates revealed that the group B [FeFe]-hydrogenases produce large amounts of H<sub>2</sub> gas and support fermentative growth of Bacteroidetes and Firmicutes. Further biochemical and spectroscopic characterization of purified enzymes show that they are catalytically active, bind a di-iron active site and reoxidize ferredoxin derived from the pyruvate:ferredoxin oxidoreductase reaction. Group B hydrogenase-encoding genes are significantly depleted in favour of other fermentative hydrogenases in patients with Crohn’s disease. Finally, metabolically flexible respiratory bacteria may be the dominant hydrogenotrophs in the gut, rather than acetogens, methanogens and sulfate reducers. These results uncover the enzymes and microorganisms controlling H<sub>2</sub> cycling in the healthy human gut.</p>

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A widespread hydrogenase supports fermentative growth of gut bacteria in healthy people

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月23日

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  • Caitlin Welsh,
  • Princess R. Cabotaje,
  • Vanessa R. Marcelino,
  • Thomas D. Watts,
  • Duncan J. Kountz,
  • Marion Jespersen,
  • Jodee A. Gould,
  • Nhu Quynh Doan,
  • James P. Lingford,
  • Thilini Koralegedara,
  • Jessica Solari,
  • Gemma L. D’Adamo,
  • Ping Huang,
  • Natasha Bong,
  • Emily L. Gulliver,
  • Remy B. Young,
  • Henrik Land,
  • Kaija Walter,
  • Isaac Cann,
  • Gabriel V. Pereira,
  • Eric C. Martens,
  • Patricia G. Wolf,
  • Jason M. Ridlon,
  • H. Rex Gaskins,
  • Edward M. Giles,
  • Dena Lyras,
  • Rachael Lappan,
  • Gustav Berggren,
  • Samuel C. Forster,
  • Chris Greening

摘要

Disruption of hydrogen (H2) cycling in the gut is linked to gastrointestinal disorders, infections and cancers. However, the mechanisms and microorganisms controlling H2 production in the gut remain unresolved. Here we show that gut H2 production is primarily driven by the microbial group B [FeFe]-hydrogenase. Metagenomics and metatranscriptomics of stool and tissue biopsy samples show that hydrogenase-encoding genes are widely present and transcribed in gut bacteria. Assessment of 19 taxonomically diverse gut isolates revealed that the group B [FeFe]-hydrogenases produce large amounts of H2 gas and support fermentative growth of Bacteroidetes and Firmicutes. Further biochemical and spectroscopic characterization of purified enzymes show that they are catalytically active, bind a di-iron active site and reoxidize ferredoxin derived from the pyruvate:ferredoxin oxidoreductase reaction. Group B hydrogenase-encoding genes are significantly depleted in favour of other fermentative hydrogenases in patients with Crohn’s disease. Finally, metabolically flexible respiratory bacteria may be the dominant hydrogenotrophs in the gut, rather than acetogens, methanogens and sulfate reducers. These results uncover the enzymes and microorganisms controlling H2 cycling in the healthy human gut.