Genes Encoding Microbial Acyl Coenzyme A Binding Protein/Diazepam-Binding Inhibitor Orthologs Are Rare in the Human Gut Microbiome and Show No Links to Obesity

Acyl coenzyme A (CoA) binding protein (ACBP), also called diazepam-binding inhibitor (DBI) is a phylogenetically conserved protein that is expressed by all eukaryotic species as well as by some bacteria. Since elevated ACBP/DBI levels play a major role in the inhibition of autophagy, increase in appetite and lipoanabolism that accompany obesity, we wondered whether ACBP/DBI produced by the human microbiome might affect host weight. We found that the genomes of bacterial commensals rarely contain ACBP/DBI homologues, which are rather encoded by genomes of some pathogenic or environmental taxa that were not prevalent in human feces. Exhaustive bioinformatic analyses of 1,899 gut samples from healthy individuals refuted the hypothesis that bacterial ACBP/DBI might affect the BMI in a physiological context. Thus, the physiological regulation of BMI is unlikely to be affected by microbial ACBP/DBI-like proteins. However, at the speculative level, it remains possible that ACBP/DBI produced by potential pathogenic bacteria might enhance their virulence by inhibiting autophagy and hence subverting innate immune responses.ImportanceAcyl coenzyme A (CoA) binding protein (ACBP) can be encoded by several organisms across the domains of life, including microbes, and has shown to play major roles in human metabolic processes. However, little is known about its presence in the human gut microbiome and whether its microbial counterpart could also play a role in human metabolism. In the present study, we found that microbial ACBP/DBI sequences were rarely present in the gut microbiome across multiple metagenomic datasets. Microbes that carried ACBP/DBI in the human gut microbiome included Saccharomyces cerevisiae, Lautropia mirabilis and Comamonas kerstersii, but these microorganisms were not associated with body-mass index, further indicating an unconvincing role for microbial ACBP/DBI in human metabolism.