A Novel Strain Bifidobacterium longum subsp. longum HN001 Ameliorates High-Fat Diet-Induced Obesity in Mice Through Microbiome-Associated Short-Chain Fatty Acids

Obesity, characterized by excessive fat accumulation, poses global health risks due to its association with metabolic diseases. Beyond conventional treatments, the gut microbiome has emerged as a promising therapeutic target. Given the critical role of microbiome alterations in obesity, modifying its composition through probiotics, prebiotics, or synbiotics offers a novel strategy for mitigating obesity and related conditions. In this study, we demonstrate the dose-dependent anti-obesity effects of a novel strain, Bifidobacterium longum subsp. longum HN001 (HN001), in a high-fat diet (HFD)-induced mouse model. Among the doses tested (100, 200, and 400 mg/kg), the 200 mg/kg dose showed the most pronounced effect, significantly reducing body weight gain, serum triglyceride (TG), and total cholesterol (TC) levels. These effects were associated with reductions in fat mass and adipocyte hypertrophy in white adipose tissue (WAT), suppression of lipogenesis, and enhanced energy expenditure through WAT browning and thermogenesis in brown adipose tissue (BAT). Microbiome analysis revealed that HN001 increased the abundance of beneficial, SCFA-producing microbes while reducing taxa linked to metabolic dysfunction. Importantly, HN001 restored serum short-chain fatty acid (SCFA) levels, and its lipid-lowering effect in adipocytes was attenuated by a GPR43 antagonist, supporting an SCFA–GPR43–mediated pathway that links microbiome modulation with reduced adipogenesis and enhanced thermogenesis. These findings suggest that HN001 may represent a promising therapeutic strategy for obesity via SCFA-driven modulation of host metabolism and gut microbiome composition. • HN001 reduces body weight and lowers serum TG and TC levels in HFD-induced obese mice. • HN001 attenuates adipocyte hypertrophy in WAT and promotes thermogenesis through browning and BAT activation. • HN001 modulates the gut microbiome, enriching beneficial taxa and restoring serum SCFA levels. • The anti-obesity effects of HN001 are partly mediated via SCFA-GPR43 signaling, supporting its therapeutic potential.