H₂metabolism is widespread and diverse among human colonic microbes

Abstract

Microbial molecular hydrogen (H 2 ) cycling is central to metabolic homeostasis and microbial composition in the human gastrointestinal tract. Molecular H 2 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 H 2 cycling. The data demonstrate that 70% of gastrointestinal microbial species listed in the Human Microbiome Project encode the genetic capacity to metabolise H 2 . A wide variety of anaerobicallyadapted 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 H 2 metabolism in the human gut is driven by fermentative H 2 production and interspecies H 2 transfer. However, it suggests that electron-bifurcation rather than respiration is the dominant mechanism of H 2 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 H 2 metabolism in the human colon.

Metabolism of hydrogen gases and bile acids in the gut microbiome

“…1). In vitro studies have shown that members of the genera Roseburia, Ruminococcus, and Eubacterium generate H 2 [25]. Another means of microbial H 2 production is through the oxidation of reduced ferredoxin (Fd) and pyridine nucleotides by microbial hydrogenases.…”

Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation

“…Microbial hydrogenogenesis and hydrogenotrophy involves the reversible oxidation of H 2 by hydrogenase harboring organisms. Categorized by their metal functional cores, hydrogenases are phylogenetically widespread and functionally diverse and include both hydrogen evolving and hydrogen uptake [NiFe] hydrogenases, hydrogen evolving [FeFe] hydrogenases, and hydrogen uptake [Fe]‐only hydrogenases . Hydrogenotrophic microbes utilize hydrogen to convert carbon dioxide to acetate (i.e., acs , fhs genes), methane ( mcrA gene), and hydrogen sulfide ( dsrA gene) .…”

“…Categorized by their metal functional cores, hydrogenases are phylogenetically widespread and functionally diverse and include both hydrogen evolving and hydrogen uptake [NiFe] hydrogenases, hydrogen evolving [FeFe] hydrogenases, and hydrogen uptake [Fe]only hydrogenases. 10 Hydrogenotrophic microbes utilize hydrogen to convert carbon dioxide to acetate (i.e., acs, fhs genes), 11 methane (mcrA gene), 12 and hydrogen sulfide (dsrA gene). 13 Conceivably, low methane production may reflect low hydrogenotrophic methanogenic abundance or low substrate availability (i.e., hydrogen), perhaps due to fewer hydrogenogenic microbes.…”

Hydrogen Therapy in Cardiovascular and Metabolic Diseases: from Bench to Bedside

“…Endogenous H 2 is catalyzed and produced by hydrogenases (H 2 ases) in bacteria, such as Escherichia coli, Bacteroidetes and Firmicutes in colon [3-5]. The great majority of H 2 ases contain iron-sulfur clusters and two metal atoms at their active center, a Ni and a Fe atom, the [NiFe]-H 2 ases, or two Fe atoms, the [FeFe]-H 2 ases [6].…”