Lactococcus lactis Subsp. lactis LL-1 and Lacticaseibacillus paracasei LP-16 Influence the Gut Microbiota and Metabolites for Anti-Obesity and Hypolipidemic Effects in Mice

This study utilized a high-fat diet-induced obese male C57BL/6 mice model to investigate the anti-obesity and lipid-lowering effects of <i>Lactococcus lactis</i> subsp. <i>lactis</i> LL-1 and <i>Lacticaseibacillus paracasei</i> LP-16. A gut microbiota analysis via 16S rRNA sequencing, along with measurements of body weight, lipids, inflammation markers, and gut metabolites, revealed that lactic acid bacteria (LAB) significantly reduced body weight, blood lipid levels, and liver oxidative stress. They also enhanced gut microbiota diversity and evenness, potentially by modulating the <i>Firmicutes</i>/<i>Bacteroidetes</i> ratio to limit excess energy absorption. Malondialdehyde (MDA) showed extremely significant positive correlations with <i>Lachnospiraceae</i>, <i>Blautia</i>, and <i>Colidextribacter</i>, and a significant positive correlation with <i>Helicobacter,</i> while superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) exhibited opposite trends. Specifically, <i>Muribaculaceae</i>, <i>Bacteroides</i>, and <i>Lactobacillus</i> showed negative correlations with MDA levels and positive correlations with SOD and GSH-Px. Short-chain fatty acids (SCFAs) positively correlated with <i>Muribaculaceae</i>, <i>Bacteroides</i>, <i>Mucispirillum</i>, and <i>Lactobacillus,</i> but negatively correlated with <i>Lachnospiraceae</i>, <i>Blautia</i>, <i>Colidextribacter</i>, <i>Alistipes</i>, and <i>Helicobacter</i>. They increased SCFA levels by promoting beneficial bacteria and reducing pathogens, alleviating obesity and hyperlipidemia. Additionally, they regulated the gut microbiota, decreasing bile acids and long-chain fatty acids while increasing SCFAs, short peptides, and vitamins, thereby improving gut metabolic disorders and enhancing host gut health.