The interaction between gut microbiota and host plays a central role in health. Dysbiosis, detrimental changes in gut microbiota and inflammation have been reported in non-communicable diseases. While diet has a profound impact on gut microbiota composition and function, the role of food additives such as titanium dioxide (TiO
2
), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO
2
on gut microbiota of mice when orally administered via drinking water. While TiO
2
had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO
2
treatment could alter the release of bacterial metabolites
in vivo
and affect the spatial distribution of commensal bacteria
in vitro
by promoting biofilm formation. We also found reduced expression of the colonic mucin 2 gene, a key component of the intestinal mucus layer, and increased expression of the beta defensin gene, indicating that TiO
2
significantly impacts gut homeostasis. These changes were associated with colonic inflammation, as shown by decreased crypt length, infiltration of CD8
+
T cells, increased macrophages as well as increased expression of inflammatory cytokines. These findings collectively show that TiO
2
is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.
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