Phylogenetic diversity of putative nickel-containing carbon monoxide dehydrogenase-encoding prokaryotes in the human gut microbiome

Although the production of carbon monoxide (CO) within the human body has been detected, only two CO-utilizing prokaryotes (CO utilizers) have been reported in the human gut. Therefore, the phylogenetic diversity of the human gut CO-utilizing prokaryotes remains unclear. Here, we unveiled more than a thousand representative genomes containing genes for putative nickel-containing CO dehydrogenase (pCODH), an essential enzyme for CO utilization. The taxonomy of genomes encoding pCODH was expanded to include 8 phyla, comprising 82 genera and 248 species. In contrast, putative molybdenum-containing CODH genes were not detected in the human gut microbial genomes. pCODH transcripts were detected in 97.3 % (<i>n</i>=110) of public metatranscriptome datasets derived from healthy human faeces, suggesting the ubiquitous presence of prokaryotes bearing transcriptionally active pCODH genes in the human gut. More than half of the pCODH-encoding genomes contain a set of genes for the autotrophic Wood-Ljungdahl pathway (WLP). However, 79 % of these genomes commonly lack a key gene for the WLP, which encodes the enzyme that synthesizes formate from CO₂, suggesting that potential human gut CO-utilizing prokaryotes share a degenerated gene set for WLP. In the other half of the pCODH-encoding genomes, seven genes, including putative genes for flavin adenine dinucleotide-dependent NAD(P) oxidoreductase (FNOR), ABC transporter and Fe-hydrogenase, were found adjacent to the pCODH gene. None of the putative genes associated with CO-oxidizing respiratory machinery, such as energy-converting hydrogenase genes, were found in pCODH-encoding genomes. This suggests that the human gut CO utilization is not for CO removal, but potentially for fixation and/or biosynthesis, consistent with the harmless yet continuous production of CO in the human gut. Our findings reveal the diversity and distribution of prokaryotes with pCODH in the human gut microbiome, suggesting their potential contribution to microbial ecosystems in human gut environments.