Synergistic effects of human-origin novel postbiotic Bacteroides & Phocaeicola on obesity and thermogenesis in high-fat diet-induced metabolic dysfunction.

Abstract

Recently, Bacteroides species, a dominant genus of commensal gut bacteria, have been increasingly recognised as potential next-generation postbiotics. The present study isolated nine Bacteroides POTENTIAL postbiotics from healthy human feces. Among them, Phocaeicola vulgatus (PV-1), Bacteroides thetaiotaomicron (BT-1), and Bacteroides uniformis (BU-1) were selected based on their capacity to inhibit lipogenesis and their potential synergy in vitro. Subsequently, the anti-obesity effect of the three Bacteroides postbiotics was comparatively investigated, both in combination (VTU) and individually, using a high-fat diet (HFD)-fed mouse model. VTU more notably reduced HFD-triggered excessive body mass, fat, and liver weights compared to the individual postbiotics. Additionally, VTU markedly attenuated serum triglyceride, total cholesterol, fasting blood glucose, and insulin levels compared to the HFD-alone treatment. Furthermore, VTU significantly downregulated the expression of lipogenesis-associated genes in the liver, including PPARγ, C/EBPα, AP2, CD36, FAS, ACC1, and LDLR, while upregulating beige-specific marker genes in the white adipose tissue, such as PRDM16, UCP1, and PPARγ. Moreover, VTU significantly altered the serum metabolomic profile, significantly changing several metabolites like lysophosphatidylcholines (LPCs) and Boc-homoglutamic acid. These findings indicate that the combination of PV-1, BU-1, and BT-1 synergistically ameliorated obesity by regulating lipid and glucose metabolism. Hence, we propose that Bacteroides postbiotics, including their combinations, could be developed as novel therapeutic agents for alleviating obesity and its complications in the future.