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.19 (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.11,27