A detoxifying multi-strain probiotic formula attenuates toxicity induced by heavy metals and phthalates

Environmental toxicants including heavy metals (lead, cadmium) and phthalate plasticizers (DEHP, DBP, DINP) are ubiquitous contaminants that enter the human body through multiple pathways, accumulate in tissues, and induce multi-organ toxicity. While chelation therapy for heavy-metal poisoning carries significant adverse effects, effective clinical management for phthalate exposure remains limited beyond exposure reduction. We therefore developed a composite probiotic formulation containing Lactiplantibacillus plantarum CCFM1019, L. plantarum CCFM259, Limosilactobacillus reuteri CCFM8631, and Bifidobacterium bifidum CCFM1258 (ratio 1:1:0.8:1.2), supplemented with inulin, raffinose, and fructo-oligosaccharides as prebiotics, to evaluate its protective efficacy against heavy-metal and phthalate toxicity. In Pb/Cd exposure models, probiotic treatment enhanced fecal metal elimination from week 2 onward, reduced tissue burdens in liver, kidney, and bone, and partially restored Ca/Fe/Zn/Mn homeostasis. Simultaneously, the intervention counteracted ALAD inhibition and dyslipidemia associated with lead exposure, elevated hepatic and renal SOD, GSH, and GPx levels while reducing MDA, and ameliorated histopathological damage in liver and kidney tissues. In DEHP/DBP/DINP exposure models, the probiotic treatment enhanced fecal and urinary excretion of parent compounds and metabolites (e.g., MEHP, MBP), diminished hepatic, renal, and testicular accumulation, and normalized ALT/AST/ALP levels and blood lipid profiles. The intervention also reduced pro-inflammatory cytokines (IL-1β, TNF-α, IL-6), restored endocrine parameters along the hypothalamic-pituitary-gonadal axis (testosterone, FSH, LH), and markedly alleviated hepatic ballooning/vacuolation and seminiferous tubule disorganization. 16S rRNA gene sequencing revealed increased α-diversity and β-diversity shifts toward control conditions, with enrichment of Lactobacillus, Bifidobacterium, and Akkermansia and suppression of Escherichia-Shigella and Turicibacter. The composite probiotic provided comprehensive protection through multiple coordinated mechanisms-promoting toxicant excretion, limiting tissue accumulation, correcting mineral/redox-inflammatory imbalances, preserving endocrine and organ function, and remodeling the gut ecosystem. Overall, the synbiotic formulation showed consistently greater benefits than the low-dose probiotic regimen and was generally comparable to the high-dose regimen across key endpoints, supporting a safe, translational nutrition-based approach for populations facing environmental exposures.