Lactobacillus protects against lead-induced hepatotoxicity by preserving the gut barrier and microbiota remodeling.

Lead (Pb) toxicity is a global health concern that primarily affects the liver. This study explored the protective effects of lactobacilli against Pb(II)-induced hepatotoxicity in mice. Three strains of lactobacilli—Lacticaseibacillus paracasei GMNL-32, Limosilactobacillus fermentum GMNL-93, and Lacticaseibacillus casei GMNL-277—were evaluated for Pb adsorption and antioxidant activity. In a chronic Pb(II) exposure mouse model, GMNL-93 and GMNL-277 more effectively mitigated Pb(II)-associated liver damage, and upregulated RNA expression of gut function-associated proteins (e.g., Cldn3, Cldn5, and Muc5). Microbiome and functional pathway analyses suggested strain-specific modes of action: GMNL-93 was associated with shifts in microbial composition and enrichment of pathways linked to redox balance and bile acid metabolism, whereas GMNL-277 was linked to enhanced thiamine-related metabolism; GMNL-32 showed comparatively limited protective. Overall, lactobacilli are promising candidates for reducing lead toxicity through directly interaction and microbiome-dependent host protection.