A probiotic for preventing microplastic toxicity: Clostridium dalinum mitigates microplastic-induced damage via microbiota-metabolism-barrier interactions

Microplastics (MPs) are widely distributed and accumulated in the environment, making it nearly impossible for humans to avoid ingestion. Their toxicity can cause serious health damage and pose a threat to human health. In this context, developing strategies to prevent and restore toxic damage from their ingestion is extremely urgent. This study comprehensively employs various techniques, including metagenomics and metabolomics, to explore the pre-protective and restorative effects of Clostridium dalinum , a potential probiotic with excellent antioxidant and anti-inflammatory capabilities, on damage induced by exposure to polystyrene microplastics (PS-MPs) in mice. The results show that exposure to PS-MPs leads to significant intestinal damage in mice; preemptive intake of C. dalinum for pre-protection, or post-exposure intake of C. dalinum for restorative treatment, both significantly reduced the damage caused by MPs exposure, as evidenced by changes in intestinal length (PS-MPs exposure vs C. dalinum pre-protection vs C. dalinum restoration vs control = 36.55 vs 39.94 vs 40.12 vs 41.05 cm), barrier protein content (27.12 % vs 97.28 % vs 97.73 % vs 100.00 %), and inflammation levels (284.56 % vs 101.05 % vs 98.17 % vs 100.00 %). Mechanistically, the pre-protective and restorative effects of C. dalinum both rely on upregulating the expression of barrier proteins such as ZO-1 and Occludin and inhibiting the TLR4/NF-κB inflammatory signaling pathway. Meanwhile, the two intervention modes also exhibit specific mechanisms: in the pre-protection mode, C. dalinum enhances lipid metabolic balance and antioxidant reserves by pre-activating the PPARγ/GPR43 pathway, and enriches the ABC transporters pathway to promote toxin efflux capacity, thereby preventing PS-MPs-induced damage; in the restoration mode, C. dalinum repairs intestinal damage by enriching the beneficial bacterium Lachnospiraceae NK4A136 and inhibiting the pro-inflammatory bacterium Desulfovibrio , and regulating intestinal metabolites. In summary, this study is the first to confirm that C. dalinum can effectively prevent and restore intestinal damage caused by PS-MPs exposure through the synergistic pathway of "microbiota-metabolism-barrier". Importantly, this study is the first to reveal the potential and unique mechanisms of probiotics in preventing and restoring MPs exposure toxicity, providing a theoretical basis for the future development of probiotic-based defense strategies. • C. dalinum prevents and restores MPs-induced gut damage. • C. dalinum enhances intestinal tight junctions, mucus layer, and ameliorates barrier. • C. dalinum counters MPs damage by multi-pathway suppressing inflammatory cascade. • C. dalinum modulates gut microbiota, fortifies microbial barrier to combat MPs damage. • C. dalinum ameliorates MPs-induced metabolic disorders and mitigates gut damage.