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

Abstract

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. Importance Acyl 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.

Alterations of the Gut Microbiome in Patients With Pituitary Adenoma

“…On the other hand, Oscillibacter sp. 57_20 was found to associate with decreased BMI [ 25 ]. Notably, a significant decrease in the abundance of the genus Oscillibacter was observed in newly diagnosed acromegaly patients with adenoma in the pituitary gland [ 13 ].…”

High plasma concentrations of acyl‐coenzyme A binding protein (ACBP) predispose to cardiovascular disease: Evidence for a phylogenetically conserved proaging function of ACBP

“…Acyl‐coenzyme A binding protein (ACBP), which is encoded by a diazepam‐binding inhibitor (DBI), is a leaderless polypeptide that can be secreted unconventionally during the activation of autophagy (Bravo‐San Pedro, Sica, Martins, Anagnostopoulos, et al, 2019 ; Duran et al, 2010 ; Manjithaya et al, 2010 ). ACBP/DBI is a phylogenetically conserved protein, the existence of which has been documented in prokaryotes (in particular in eubacteria) as well as in all major eukaryotic kingdoms including animals, fungi, and plants (Du et al, 2016 ; Thomas et al, 2021 ). Its autophagy‐dependent release has been reported in unicellular and multicellular fungi (Duran et al, 2010 ; Manjithaya et al, 2010 ) as well as in human and murine cells (Bravo‐San Pedro, Sica, Martins, Anagnostopoulos, et al, 2019 ; Loomis et al, 2010 ).…”

ACBP/DBI protein neutralization confers autophagy-dependent organ protection through inhibition of cell loss, inflammation, and fibrosis

“…Moreover, induction of polyclonal autoantibodies capable of neutralizing ACBP/DBI failed to induce visible side effects over several months. It is remarkable, however, that the liver disease–attenuating effects of α-DBI are mimicked by those of the inducible Dbi knockout, constitutive mutation of the ACBP/DBI receptor, as well as by the induction of autoantibodies, strongly arguing in favor of the hypothesis that α-DBI acts on target rather than by recognizing additional host genome–encoded or microbial proteins that structurally resemble ACBP/DBI ( 60 , 61 ).…”