Modulation of satiety hormones by Bacteroides thetaiotaomicron, Bacteroides fragilis and their derivatives

Obesity is a complex disorder influenced by various factors, including gut microbiota, which play a crucial role in metabolic regulation. This study is aimed to investigate the effects of Bacteroides thetaiotaomicron and Bacteroides fragilis, along with their derivatives-outer membrane vesicles (OMVs) and cell-free supernatant (CFS)-on the expression and secretion of satiety hormones in the murine intestinal secretin tumor cell line (STC-1). We examined the expression of peptide YY (PYY), glucagon-like peptide-1 and -2 (GLP-1 and GLP-2, encoded by the GCG gene), the enzyme prohormone convertase-1 (PC1/PCSK1 gene), and the receptors G protein-coupled receptor 119 and 120 (GPR119 and GPR120), and G-protein-coupled bile acid receptor (TGR5). Our results demonstrate that live B. fragilis significantly increased PYY expression and secretion. B. thetaiotaomicron CFS notably upregulated GCG, PCSK1, GPR119, GPR120, and TGR5 expression, leading to elevated GLP-1 secretion. B. fragilis CFS decreased GPR119, GPR120, and GCG expression. OMVs from B. thetaiotaomicron at 50 µg/ml significantly enhanced GCG and PCSK1 expression, while B. fragilis OMVs generally decreased gene expression, except for PYY protein abundance. Inactive B. thetaiotaomicron and B. fragilis increased GCG mRNA levels and GLP-1 concentration, with inactive B. fragilis also elevating GLP-2 protein levels.This study suggests that B. thetaiotaomicron and its derivatives, particularly CFS and OMVs, have potential as next-generation probiotics, postbiotics, and paraprobiotics for modulating satiety hormones and managing obesity. Further research is warranted to explore their mechanisms and therapeutic applications in vivo.