**5. Conclusions**

In conclusion, in vivo consumption of TiO2 could alter the composition and the activity of intestinal bacteria, promoting an inflammatory environment in the gu<sup>t</sup> and aggravating gu<sup>t</sup> barrier impairment and immune responses in animals already affected by diseases such as colitis or obesity. Therefore, although these findings did not allow us to reach firm conclusions in humans, this systematic review highlights the key role of gu<sup>t</sup> microbiota in nanotoxicology in the gu<sup>t</sup> and stimulates discussions on the safe TiO2 use in food and dietary supplements.

**Supplementary Materials:** The following are available online at https://www.mdpi.com/1660-4 601/18/4/2008/s1, Table S1. PRISMA checklist; Table S2. Search strategy; Table S3. Reporting of in vivo experiments (ARRIVE) guideline assessment for the included animal studies; Table S4. SCYRCLE's tool for assessing the risk of bias in animal studies.

**Author Contributions:** Conceptualization, E.R. and P.R.; methodology, P.R.; validation, M.C.M. and A.G.; investigation, M.C.; resources, V.M.; writing—original draft preparation, P.R.; writing—review and editing, E.R.; visualization, A.G.; supervision, M.C.M. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding. **Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.
