Lactobacillus rhamnosus B16 regulates lipid metabolism homeostasis by producing acetic acid

Hyperlipidemia, a chronic disorder caused by abnormal lipid metabolism, increases risks of atherosclerosis and cardiovascular diseases. Current single-target drugs have limited efficacy and side effects, prompting interest in probiotics such as Lactobacillus rhamnosus, though their mechanisms remain unclear.

A novel Lactobacillus rhamnosus strain from healthy human feces was identified via API 50CH and ANI analysis. Integrated genomic and proteomic analyses were performed on the novel Lactobacillus rhamnosus B16 (L. rB16) strain to characterize its lipid metabolism-related traits. A cholesterol degradation assay, gastrointestinal fluid tolerance test, and biofilm formation assay were used to evaluate the functional properties of L. rB16, while foam cell models were employed to assess its cholesterol-lowering effects. Western blotting was used to determine the expression levels of key lipid metabolism-associated proteins (LXRα, ABCA1, ABCG1, HMGCR, and SREBP1) in foam cells treated with heat-inactivated L. rB16 (HI-L. rB16). For in vivo validation, a high-fat diet (HFD)-induced hyperlipidemic mouse model was established, and analyses including serum lipid profiling, histological examination, and immunohistochemical staining were conducted. Metabolomic and short-chain fatty acids (SCFAs) analyses identified key metabolites, validated by sodium acetate treatment.

We identified a novel strain of L. rB16 from healthy human feces, which had cholesterol-lowering ability in a cholesterol-enriched MRS broth. Moreover, we found that HI-L. rB16 could reduce foam cell cholesterol levels through the Liver X receptor alpha (LXRα) signaling pathway and regulate hepatic lipid metabolism balance by regulating the expression of key lipid proteins. Metabolomics showed the acetic acid produced by HI-L. rB16 was the main metabolite that exerted the cholesterol-lowering effect.

HI-L. rB16 alleviates HFD-induced hyperlipidemia in mice by reducing cholesterol through acetate-mediated LXRα signaling, demonstrating its therapeutic potential as a probiotic for lipid metabolism disorders.