Bifidobacterium animalis subsp. animalis GY007 Mitigates High Fluoride Exposure-Induced Ileal Injury and Restores the Ileal Microbiota–Metabolome Imbalances

Exposure to fluoride is strongly associated with impaired intestinal function. Probiotics are widely regarded as an effective strategy to maintain microbial homeostasis and to mitigate the progression of fluoride-induced intestinal injury. This study aimed to evaluate the measurable protective effects of the probiotic strain Bifidobacterium animalis subsp. animalis (B. animalis subsp. animalis) GY007 in reversing high fluoride-induced ileal injury. The results showed that GY007 (1 × 109 CFU/mL, once/daily) attenuated intestinal barrier disruption and alleviated ileal mucosal abnormalities in mice receiving fluoride (24 mg/kg) by gavage for eight consecutive weeks. GY007 attenuated elevated oxidative stress and modulated the inflammatory response associated with the TLR9/NF-κb/IRF7 signaling pathway. Microbiome and metabolomic analyses showed that GY007 reversed the dysregulation of the ileal microbial community structure and metabolite profiles. Spearman’s rank correlation analysis further supported a regulatory role for Bifidobacterium in this protective process and identified three key functional metabolites meriting further investigation: isocytosine (ISO), 7α,24S-dihydroxy-3-oxocholest-4-en-26-oic acid (OIC-7α), and sinapinic acid (SIA). Our findings demonstrate that GY007 protects against fluoride-induced ileal injury and elucidate the associated changes in the intestinal microbial community and metabolite profiles. This study provides new evidence clarifying the restorative effect of the probiotic GY007 on the ileum under environmental fluoride exposure, offering an integrative perspective on the interaction between microorganisms and their host.