Impact of food additive titanium dioxide on gut microbiota composition, microbiota‐associated functions, and gut barrier: A systematic review of in vivo animal studies

Background: Titanium dioxide (TiO2) is used as a food additive in pastries, sweets, and sauces. It is recognized as safe by food safety authorities, but in recent years, governments and sci-entists have raised concerns about its genotoxicity. This systematic review aims to assess the potential associations between food TiO2 exposure and microbiota composition and functions. Methods: A systematic literature search was performed up to December 2020 in PubMed, Web of Science, and Scopus databases. The PRISMA guidelines followed. The risk of bias was assessed from ARRIVE and SYRCLE tools. Results: A total of 18 animal studies were included (n = 10 mice, n = 5 rats, n = 2 fruit flies, n = 1 silkworm). Studies varied significantly in protocols and outcomes assessment. TiO2 exposure might cause variations in abundance in specific bacterial species and lead to gut dysfunc-tions such as a reduction in SCFAs levels, goblet cells and crypts, mucus production, and increased biomarkers of intestinal inflammation. Conclusions: Although the extrapolation of these results from animals to humans remains difficult, this review highlights the key role of gut microbiota in gut nanotoxicology and stimulates discussions on the safe TiO2 use in food and dietary supple-ments. This systematic review was registered at PROSPERO as CRD42020223968.