Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 May 3;7(3):235-45.
doi: 10.1080/19490976.2016.1182288.

H2 Metabolism Is Widespread and Diverse Among Human Colonic Microbes

Affiliations
Free PMC article

H2 Metabolism Is Widespread and Diverse Among Human Colonic Microbes

Patricia G Wolf et al. Gut Microbes. .
Free PMC article

Abstract

Microbial molecular hydrogen (H2) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H2 is produced as an endproduct of carbohydrate fermentation and is reoxidised primarily by sulfate-reduction, acetogenesis, and methanogenesis. However, the enzymatic basis for these processes is incompletely understood and the hydrogenases responsible have not been investigated. In this work, we surveyed the genomic and metagenomic distribution of hydrogenase-encoding genes in the human colon to infer dominant mechanisms of H2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H2. A wide variety of anaerobically-adapted hydrogenases were present, with [FeFe]-hydrogenases predominant. We subsequently analyzed the hydrogenase gene content of stools from 20 healthy human subjects. The hydrogenase gene content of all samples was overwhelmingly dominated by fermentative and electron-bifurcating [FeFe]-hydrogenases emerging from the Bacteroidetes and Firmicutes. This study supports that H2 metabolism in the human gut is driven by fermentative H2 production and interspecies H2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H2 reoxidation in the human colon, generating reduced ferredoxin to sustain carbon-fixation (e.g. acetogenesis) and respiration (via the Rnf complex). This work provides the first comprehensive bioinformatic insight into the mechanisms of H2 metabolism in the human colon.

Keywords: electron-bifurcation; hydrogen; hydrogenase; hydrogenogen; hydrogenotroph; interspecies H2 transfer.

Figures

Figure 1.
Figure 1.
Genomic distribution of hydrogenases in human colonic microorganisms. (A) The proportion of microbial species that encode hydrogenases. This was determined using the 343 microbial species represented in the Human Microbiome Project Gastrointestinal Tract (HMP GI) genome database. (B) Distribution of human colonic hydrogenase sequences by microbial phyla and hydrogenase class. Hydrogenase sequences were obtained from human colonic microorganisms represented in the NCBI Reference Sequence database and were classified according to previously-outlined criteria.
Figure 2.
Figure 2.
Phylogenetic trees showing the diversity of the human colonic hydrogenases. The trees represent the protein sequences of the [FeFe]-hydrogenase catalytic domains (A) and [NiFe]-hydrogenase catalytic subunits (B) derived from the genomes of human colonic microorganisms. The trees were constructed by the neighbor-joining method, are bootstrapped with 500 replicates, and are color -coded by hydrogenase class.
Figure 3.
Figure 3.
Distribution of hydrogenase-encoding genes in human colonic metagenomes. The hydrogenase content of 20 metagenomes derived from the HMP GI metagenome database was determined at a depth of 5 million reads. (A) Probable phylum-level affiliation of hydrogenases detected. This was determined by recording the closest BLAST hit for each read against a databank of 3284 hydrogenase sequences. (B) Number of reads corresponding to each [FeFe]-hydrogenase class. (C) Number of reads corresponding to each [NiFe]-hydrogenase class.
Figure 4.
Figure 4.
Summary of human colon H2 metabolism based on the described genome and metagenome surveys. (A) Summary of the predominant known routes of H2 evolution and reoxidation in the human colon. The microbial phyla and hydrogenase classes mediating these processes are shown. The hydrogenases are sized according to the relative abundance of the genes encoding them in the 20 metagenomes surveyed. The most dominant hydrogenogenic hydrogenases were the Group A1 and Group B [FeFe]-hydrogenases that mediate ferredoxin-dependent H2 evolution. NADPH- or formate-dependent H2 evolution appears to be quantitatively less important. The electron-bifurcating Group A3 [FeFe]-hydrogenases were by far the most abundant hydrogenotrophic hydrogenases identified in our genome and metagenome surveys. These enzymes are linked to acetogenesis, though our metagenomes surveys suggest that many hydrogenotrophs are also capable of oxidising H2 without producing detectable endproducts, i.e. through H2-mediated ferredoxin reduction followed by subsequent ferredoxin respiration. The determinants of hydrogenotrophic methanogenesis, sulfate reduction, and fumarate reduction were identified, but appear to be comparatively rare. (B) Simplified pathways showing interspecies hydrogen transfer between the 2 most dominant H2-metabolising phyla in the human colon. The H2 evolved by a carbohydrate-fermenting Bacteroides species by the [FeFe] Group B hydrogenase. The H2 is transferred to a hydrogenotroph of the genus Clostridium and is bifurcated at [FeFe] Group A3 to reduce ferredoxin and NADH. The derived reductant sustains respiration through the Rnf complex and CO2 fixation through reductive acetogenesis. Our survey suggests alternative pathways may also occur in the human colon resulting in H2 oxidation in Firmicutes, H2 production in Bacteroidetes, and internal recycling of H2. It is probable that the [FeFe] Group A3 hydrogenase can generate reductant in Firmicutes and Bacteroidetes independently of acetogenesis. Key: Nuo = NADH dehydrogenase, Frd = fumarate reductase, Rnf = ferredoxin:NAD+ oxidoreductase. Modeled based on references.

Similar articles

See all similar articles

Cited by 26 articles

See all "Cited by" articles

Publication types

Feedback