Foodborne Titanium Dioxide Nanoparticles Induce Stronger Adverse Effects in Obese Mice than Non‐Obese Mice: Gut Microbiota Dysbiosis, Colonic Inflammation, and Proteome Alterations

Abstract

The recent ban of titanium dioxide (TiO2) as a food additive (E171) in France intensified the controversy on safety of foodborne‐TiO2 nanoparticles (NPs). This study determines the biological effects of TiO2 NPs and TiO2 (E171) in obese and non‐obese mice. Oral consumption (0.1 wt% in diet for 8 weeks) of TiO2 (E171, 112 nm) and TiO2 NPs (33 nm) does not cause severe toxicity in mice, but significantly alters composition of gut microbiota, for example, increased abundance of Firmicutes phylum and decreased abundance of Bacteroidetes phylum and Bifidobacterium and Lactobacillus genera, which are accompanied by decreased cecal levels of short‐chain fatty acids. Both TiO2 (E171) and TiO2 NPs increase abundance of pro‐inflammatory immune cells and cytokines in the colonic mucosa, indicating an inflammatory state. Importantly, TiO2 NPs cause stronger colonic inflammation than TiO2 (E171), and obese mice are more susceptible to the effects. A microbiota transplant study demonstrates that altered fecal microbiota by TiO2 NPs directly mediate inflammatory responses in the mouse colon. Furthermore, proteomic analysis shows that TiO2 NPs cause more alterations in multiple pathways in the liver and colon of obese mice than non‐obese mice. This study provides important information on the health effects of foodborne inorganic nanoparticles.

Four Types of TiO2 Reduced the Growth of Selected Lactic Acid Bacteria Strains

“…Mu et al [ 38 ] reported that administration of TiO 2 NPs (10 and 50 nm) to young weaned mice for 2–3 months in the diet reduced the numbers of Bifidobacterium and Lactobacillus , which led to weight loss. In in vivo study conducted by Cao et al [ 11 ], oral administration of TiO 2 (E171, 112 nm) and TiO 2 NPs (33 nm) to obese and non-obese mice (0.1% w/w in the diet for 8 weeks) resulted in a significant reduction in the intestinal amounts of Bifidobacterium and Lactobacillus bacteria count number. The authors found that TiO 2 NPs induced more severe colon inflammation than TiO 2 (E171), especially in the more susceptible obese mice, which was also associated with their high-fat diet.…”

“…The authors found that TiO 2 NPs induced more severe colon inflammation than TiO 2 (E171), especially in the more susceptible obese mice, which was also associated with their high-fat diet. Authors suggested that TiO 2 exposure of mice with reduced levels of Bifidobacterium and Lactobacillus may result in increased susceptibility to such diseases as irritable bowel syndrome [ 11 ].…”

“…In recent years, the use of titanium dioxide as a food additive (E171) has raised considerable controversy [ 11 , 12 , 13 ]. For instance, France was the first country to prohibit the use of this food additive for fear of its potential harmfulness [ 11 ].…”

“…In recent years, the use of titanium dioxide as a food additive (E171) has raised considerable controversy [ 11 , 12 , 13 ]. For instance, France was the first country to prohibit the use of this food additive for fear of its potential harmfulness [ 11 ]. Its presence is increasingly often associated with disorders of the intestinal barrier, including intestinal dysbiosis [ 4 , 14 , 15 ].…”

Toxicity Assessment of SiO2 and TiO2 in Normal Colon Cells, In Vivo and in Human Colon Organoids

“…SiO 2 and TiO 2 nanoparticles can also induce cytotoxicity and thus may have a negative health impact. These studies have shown that SiO 2 and TiO 2 nanoparticles show toxicity in the human lung, intestinal cells and during in vivo experiments [14][15][16][17][18][19].…”