Lacticaseibacillus rhamnosus CU262 Attenuates High-Fat Diet-Induced Obesity via Gut-Liver Axis Reprogramming

Area of Science:

• Microbiology
• Metabolic Health
• Gut-Liver Axis Research

Background:

• Obesity is linked to gut dysbiosis, dyslipidemia, and liver injury.
• The gut-liver axis plays a critical role in metabolic homeostasis.
• Targeting the gut microbiota offers a potential strategy for obesity management.

Purpose of the Study:

• To evaluate the anti-obesity effects of Lacticaseibacillus rhamnosus CU262.
• To elucidate the underlying mechanisms using a multi-omics approach.
• To assess the impact on gut microbiota, host metabolism, and liver function.

Main Methods:

• A high-fat diet (HFD) mouse model was used.
• Mice were supplemented with L. rhamnosus CU262 for 12 weeks.
• Integrated analysis of phenotypes, serum/liver biochemistry, 16S rRNA sequencing, fecal SCFAs, and RNA-seq was performed.

Main Results:

• CU262 significantly reduced weight gain, adiposity, and improved lipid profiles (TC, TG, LDL-C, HDL-C).
• It lowered liver enzymes (ALT/AST), reduced inflammation (IL-6, TNF-α), and mitigated oxidative stress.
• CU262 modulated gut microbiota composition, increased beneficial bacteria (Akkermansia), and boosted SCFA production (acetate, butyrate).
• Hepatic transcriptomics revealed reversal of HFD-induced cholesterol biosynthesis and ER stress, with enhanced oxidative phosphorylation and glutathione metabolism.

Conclusions:

• Lacticaseibacillus rhamnosus CU262 demonstrates significant anti-obesity effects in an HFD mouse model.
• The probiotic acts through reprogramming the gut microbiota-SCFA-hepatic gene network along the gut-liver axis.
• CU262 shows potential as a functional probiotic for managing obesity and associated metabolic disorders.