Phylogenetic diversity of the carbon monoxide-utilizing prokaryotes and their divergent carbon monoxide metabolisms in the human gut microbiome

Abstract

Although the production of toxic CO within the human body has been detected, only a few CO-utilizing prokaryotes (CO utilizers) have been reported in the human gut, and their phylogenetic and physiological diversity remains unclear. Here, we unveiled more than thousand representative genomes originating from previously unexplored potential CO-utilizing prokaryotes, which contain CO dehydrogenase (CODH) genes. More than half of CODH-bearing prokaryotes possess genes for the autotrophic Wood-Ljungdahl pathway (WLP). However, 95% of these prokaryotes commonly lack a key gene for WLP, which encodes enzyme that synthesizes formate from CO2 and H2, suggesting that they share a degenerated WLP. Instead, many were predicted to possess an alternative way of synthesizing formate from pyruvate, which is a product of glycolysis. This suggests that glycolysis may serve as a potential supplier of carbon and reducing power to degenerate WLP, which may no longer function as a complete autotrophic pathway. In addition to degenerated WLP, one of the seven predicted CO metabolic pathways involves CO oxidation, which is linked to nitrate reduction and oxaloacetate synthesis. Our findings reveal the unique and diverse nature of CO metabolism in the human gut microbiome, suggesting its potential contribution to CO consumption and gut homeostasis.