Lactobacillus probiotics attenuate hyperlipidemia and fatty liver in rat via LPS and 5-HT-related signaling axis

This study aims to explore the mechanism of action of three Lactobacillus, Lactiplantibacillus plantarum (Lp), Lactobacillus fermentum (Lf), and Lactobacillus brevis (Lb), in alleviating hyperlipidemia and fatty liver induced by a high-fat diet (HFD) in rats. Wistar rats were fed an HFD to induce hyperlipidemia and fatty liver. The effects of the three probiotic strains were assessed by analyzing blood lipids, inflammatory markers, oxidative stress, key signaling pathways, and fecal short-chain fatty acids (SCFAs). Their anti-lipidemic effect was further verified in C. elegans. The probiotics suppressed weight gain, hyperlipidemia, and liver injury. They modulated lipid metabolism, reduced inflammation and oxidative stress by deactivating the TLR4/MyD88/NF-κB pathway, and inhibited hepatic ferroptosis via the Nrf2/GPX4 pathway. They also increased fecal lipid excretion and SCFA production. SCFAs (acetate, propionate, butyrate) alone alleviated lipid deposition in C. elegans. The three Lactobacillus strains effectively protected against HFD-induced liver injury by modulating multiple pathways related to inflammation, lipid metabolism, and ferroptosis, with SCFAs being a potential contributing factor.