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Impact of Food Additive Titanium Dioxide on Gut Microbiota Composition, Microbiota-Associated Functions, and Gut Barrier: A Systematic Review of In Vivo Animal Studies.

ABSTRACT: 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 scientists have raised concerns about its genotoxicity. This systematic review aims to assess the potential associations between food TiO2 exposure and microbiota composition and functions. 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. 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 dysfunctions such as a reduction in SCFAs levels, goblet cells and crypts, mucus production, and increased biomarkers of intestinal inflammation. 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 supplements. This systematic review was registered at PROSPERO as CRD42020223968.

SUBMITTER: Rinninella E

PROVIDER: S-EPMC7922260 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Impact of Food Additive Titanium Dioxide on Gut Microbiota Composition, Microbiota-Associated Functions, and Gut Barrier: A Systematic Review of In Vivo Animal Studies.

Rinninella Emanuele E Cintoni Marco M Raoul Pauline P Mora Vincenzina V Gasbarrini Antonio A Gasbarrini Antonio A Mele Maria Cristina MC

International journal of environmental research and public health 20210219 4

<h4>Background</h4>Titanium dioxide (TiO<sub>2</sub>) 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 scientists have raised concerns about its genotoxicity. This systematic review aims to assess the potential associations between food TiO<sub>2</sub> exposure and microbiota composition and functions.<h4>Methods</h4>A systematic literature search was performed up to December 2020 in PubMed, Web ...[more]

PMID: 33669592

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Project description:ObjectiveUp to 44% of particulates of food-grade titanium dioxide (TiO2) are in nanoscale, while the effect and combined effect of which with other substances on intestinal barrier haven't been fully understood yet. This study is aimed to study the effect of two kinds of TiO2 nanoparticles (TiO2 NPs and TiO2 MPs) on intestinal barrier functions, to reveal the combined effect of TiO2 NPs and Lipopolysaccharide (LPS) on intestinal barrier.MethodsMale ICR mice were randomly divided into 18 groups (3 feed types * 3 exposure length * 2 LPS dosage) and were fed with normal or TiO2-mixed feed (containing 1% (mass fraction, w/w) TiO2 NPs or TiO2 MPs) for 1, 3, 6 months, followed by a single oral administration of 0 or 10 mg/(kg body weight) LPS. Four hours later, the transportation of TiO2, the intestinal barrier functions and the inflammatory response were evaluated.ResultsBoth TiO2 notably increased the intestinal villi height / crypt depth ratios after 1 and 3 months of exposure, and increased the expression of ileal tight junction proteins (ZO-1 and occludin) after 1 month of exposure. After 6 months of exposure, TiO2 NPs led to reduced feed consumption, TiO2 MPs caused spare microvilli in small intestine and elevated Ti content in the blood cells. The intestinal permeability didn't change in both TiO2 exposed groups. After LPS administration, we observed altered intestinal villi height / crypt depth ratios, lowered intestinal permeability (DAO) and upregulated expression of ileal ZO-1 in both (TiO2 +LPS) exposed groups. There are no significant changes of ileal or serum cytokines except for a higher serum TNF-α level in LPS treated group. The antagonistic effect was found between TiO2 NPs and LPS, but there are complicated interactions between TiO2 MPs and LPS.ConclusionLong-term intake of food additive TiO2 could alter the intestinal epithelial structure without influencing intestinal barrier function. Co-exposure of TiO2 and LPS would enhance intestinal barrier function without causing notable inflammatory responses, and there is antagonistic effect between TiO2 NPs and LPS. All the minor effects observed might associate with the gentle exposure method where TiO2 being ingested with feed.

Project description:The present opinion deals with an updated safety assessment of the food additive titanium dioxide (E 171) based on new relevant scientific evidence considered by the Panel to be reliable, including data obtained with TiO2 nanoparticles (NPs) and data from an extended one-generation reproductive toxicity (EOGRT) study. Less than 50% of constituent particles by number in E 171 have a minimum external dimension < 100 nm. In addition, the Panel noted that constituent particles < 30 nm amounted to less than 1% of particles by number. The Panel therefore considered that studies with TiO2 NPs < 30 nm were of limited relevance to the safety assessment of E 171. The Panel concluded that although gastrointestinal absorption of TiO2 particles is low, they may accumulate in the body. Studies on general and organ toxicity did not indicate adverse effects with either E 171 up to a dose of 1,000 mg/kg body weight (bw) per day or with TiO2 NPs (> 30 nm) up to the highest dose tested of 100 mg/kg bw per day. No effects on reproductive and developmental toxicity were observed up to a dose of 1,000 mg E 171/kg bw per day, the highest dose tested in the EOGRT study. However, observations of potential immunotoxicity and inflammation with E 171 and potential neurotoxicity with TiO2 NPs, together with the potential induction of aberrant crypt foci with E 171, may indicate adverse effects. With respect to genotoxicity, the Panel concluded that TiO2 particles have the potential to induce DNA strand breaks and chromosomal damage, but not gene mutations. No clear correlation was observed between the physico-chemical properties of TiO2 particles and the outcome of either in vitro or in vivo genotoxicity assays. A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out. Several modes of action for the genotoxicity may operate in parallel and the relative contributions of different molecular mechanisms elicited by TiO2 particles are not known. There was uncertainty as to whether a threshold mode of action could be assumed. In addition, a cut-off value for TiO2 particle size with respect to genotoxicity could not be identified. No appropriately designed study was available to investigate the potential carcinogenic effects of TiO2 NPs. Based on all the evidence available, a concern for genotoxicity could not be ruled out, and given the many uncertainties, the Panel concluded that E 171 can no longer be considered as safe when used as a food additive.

Dataset Information

Impact of Food Additive Titanium Dioxide on Gut Microbiota Composition, Microbiota-Associated Functions, and Gut Barrier: A Systematic Review of In Vivo Animal Studies.

Publications

Impact of Food Additive Titanium Dioxide on Gut Microbiota Composition, Microbiota-Associated Functions, and Gut Barrier: A Systematic Review of In Vivo Animal Studies.

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