Postbiotics from Lacticaseibacillus rhamnosus IOB820 Combat Obesity in HFD Mice by Modulating Gut Microbiota and Enhancing SCFA Production

<b>Aims:</b> To evaluate whether <i>Lacticaseibacillus rhamnosus</i> (<i>L. rhamnosus</i>) IOB820 and its postbiotics can combat high-fat diet (HFD)-induced obesity, improve metabolic parameters, and modulate gut microbiota and systemic inflammation in a mouse model. <b>Methods:</b> Seventy 4-week-old male C57BL/6J mice were divided into a normal diet group, an HFD control group, two postbiotic dose groups, two live bacteria dose groups, and an orlistat control group. After 10 weeks of intervention with live <i>L. rhamnosus</i> IOB820 or its postbiotics, body weight, metabolic parameters (blood glucose, lipid profile, hepatic steatosis), pro- and anti-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10), gut microbiota composition (α, β diversity and taxonomic shifts), and fecal short-chain fatty acid (SCFA) levels were assessed. <b>Results:</b> Both live <i>L. rhamnosus</i> IOB820 and its postbiotics significantly alleviated HFD-induced weight gain and improved metabolic outcomes. The treatments also reduced systemic inflammation, as indicated by decreased levels of TNF-α, IL-6, and IL-1β and elevated IL-10. These effects were accompanied by restoration of gut microbial diversity, enrichment of beneficial taxa, and increased fecal SCFA concentrations. <b>Conclusions:</b><i>L. rhamnosus</i> IOB820 and its postbiotics effectively mitigate obesity and related metabolic disturbances in HFD-fed mice. Their beneficial effects are likely mediated through modulation of gut microbiota composition and enhancement of SCFA-driven anti-inflammatory responses.