Abstract

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 (TiO2), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO2 on gut microbiota of mice when orally administered via drinking water. While TiO2 had minimal impact on the composition of the microbiota in the small intestine and colon, we found that TiO2 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 TiO2 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 TiO2 is not inert, but rather impairs gut homeostasis which may in turn prime the host for disease development.

Highlights

  • Bacterial species that inhabit the colon interact with the host, promoting the development and function of immune cells locally and systemically

  • We employed dynamic light scattering (DLS) to determine the hydrodynamic size of the E171 product used in this study

  • We employed nanoparticle tracking analysis (NTA) and scanning electron microscopy (SEM) to further investigate the size and shape of the TiO2 nanoparticles dispersed in drinking water

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Summary

Introduction

Bacterial species that inhabit the colon interact with the host, promoting the development and function of immune cells locally and systemically. Alterations in antimicrobial peptide production, mucus layer thickness and/or epithelial permeability have been implicated in the development of a broad range of diseases such as colitis and colorectal cancer [10]. These diseases have been linked to abnormal interactions between the host epithelium and the gut microbiota through the formation of biofilm. The mechanisms behind the formation and the role of biofilm in the gut are not fully understood, but biofilm formation has been shown to impact both disease development and resolution Both in a colitis rat model and in humans, biofilm in the colon has been shown to facilitate pathobiont adherence to the epithelium and translocation to the host [12, 13]. A recent study has shown that inoculation of germ-free mice with biofilm positive human colon inocula was carcinogenic [15]

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