| Summary: | Titanium dioxide nanoparticles (TiO<sub>2</sub> NPs) are generally added in considerable amounts to food as a food additive. Oral exposure to TiO<sub>2</sub> NPs could induce intestinal damage, especially in obese individuals with a high-fat diet. The probiotic <i>Bacillus coagulans</i> (<i>B. coagulans</i>) exhibits good resistance in the gastrointestinal system and is beneficial to intestinal health. In this study, <i>B. coagulans</i> was used to treat intestinal damage caused by TiO<sub>2</sub> NPs in high-fat-diet mice via two intervention methods: administration of TiO<sub>2</sub> NPs and <i>B. coagulans</i> simultaneously and administration of TiO<sub>2</sub> NPs followed by that of <i>B. coagulans</i>. The intervention with <i>B. coagulans</i> was found to reduce the inflammatory response and oxidative stress. A 16S rDNA sequencing analysis revealed that <i>B. coagulans</i> had increased the diversity of gut microbiota and optimized the composition of gut microbiota. Fecal metabolomics analysis indicated that <i>B. coagulans</i> had restored the homeostasis of sphingolipids and amino acid metabolism. The intervention strategy of administering TiO<sub>2</sub> NPs followed by <i>B. coagulans</i> was found to be more effective. In conclusion, <i>B. coagulans</i> could alleviate intestinal damage induced by TiO<sub>2</sub> NPs in high-fat-diet mice TiO<sub>2</sub><i>B. coagulans</i>. Our results suggest a new avenue for interventions against intestinal damage induced by TiO<sub>2</sub> NPs.
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