Lactobacillus johnsonii BS15 Alleviates Fluoride-Induced Intestinal Barrier Injury by Regulating the RhoA/ROCK-Mediated Cytoskeletal Remodeling.

Abstract

Chronic fluoride exposure is a significant environmental health concern known to induce severe intestinal barrier dysfunction and systemic toxicity. This study investigated the protective effects and underlying mechanisms of Lactobacillus johnsonii BS15 (L. johnsonii BS15) against fluoride-induced intestinal barrier injury in mice. Our results demonstrated that L. johnsonii BS15 intervention ameliorated multifaceted damage caused by high fluoride exposure at functional, structural and oxidative levels: it lowered serum concentration of diamine oxidase (DAO), a marker of intestinal barrier damage; mitigated intestinal pathological lesions including crypt hyperplasia and reduced villus‑to‑crypt ratio; and suppressed oxidative‑stress‑related upregulation of ileal Duox2/Duoxa2 mRNA. Mechanistically, L. johnsonii BS15 inhibited the fluoride-induced elevation of the RhoA/ROCK/p-MLC signaling axis, consequently mitigating pathological F-actin stress fiber polymerization and restoring cytoskeletal dynamic equilibrium. L. johnsonii BS15 intervention restored the integrity of the tight junction complex by restoring the membrane localization and expression levels of ZO-1 and Claudin-1, repairing the membrane continuity of Occludin, and inhibiting the abnormal translocation and accumulation of β-catenin into the cytoplasm. In conclusion, high fluoride-induced intestinal barrier dysfunction was attenuated in mice receiving L. johnsonii BS15, a process involving downregulation of the RhoA/ROCK pathway and downregulation of oxidative stress‑related Duox2/Duoxa2 mRNA expression. These findings reveal a potential microbiota-based intervention strategy and provide new insights for the prevention and treatment of fluorosis.