Gut Bacteria Use Hydrogen Gas to Stay Healthy and Fight Disease
- Authors
- 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
- Journal
- Nature Microbiology
- Year
- 2025
- DOI
- 10.1038/s41564-025-02154-w
- Study Type
- Human
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Australia
- Health Condition
- Crohn's Disease
- Body System
- Digestive
TL;DR
Group B [FeFe]-hydrogenases are key microbial drivers of hydrogen (H₂) production in the human gut; their depletion in Crohn’s disease may disrupt gut H₂ cycling and microbial balance.
Key Finding
Group B [FeFe]-hydrogenases are the primary drivers of hydrogen gas production in the healthy human gut, and these enzymes are significantly depleted in patients with Crohn's disease.
Summary
Researchers studied how bacteria in the healthy human gut produce hydrogen gas and found that a specific type of enzyme called group B [FeFe]-hydrogenase is responsible for most of this production. By analyzing gut bacteria samples from healthy people and those with Crohn's disease (an inflammatory bowel condition), they discovered that these enzymes help bacteria break down food and generate energy. Importantly, people with Crohn's disease had significantly lower levels of these hydrogen-producing enzymes, suggesting that disrupted hydrogen cycling in the gut may be connected to inflammatory bowel disease.
Practical Takeaway
This research identifies a specific mechanism by which gut bacteria produce hydrogen and suggests that impaired hydrogen cycling may contribute to inflammatory bowel disease. However, this study focuses on understanding natural hydrogen production in the gut rather than the effects of consuming hydrogen water, so its direct relevance to hydrogen water supplementation remains unclear. Further research would be needed to determine whether external hydrogen administration could restore or compensate for depleted hydrogen-producing capacity in people with gastrointestinal disorders.
Abstract
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.