Dataset Information

Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

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.

SUBMITTER: Pinget G

PROVIDER: S-EPMC6534185 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

Pinget Gabriela G Tan Jian J Janac Bartlomiej B Kaakoush Nadeem O NO Angelatos Alexandra Sophie AS O'Sullivan John J Koay Yen Chin YC Sierro Frederic F Davis Joel J Divakarla Shiva Kamini SK Khanal Dipesh D Moore Robert J RJ Stanley Dragana D Chrzanowski Wojciech W Macia Laurence L

Frontiers in nutrition 20190514

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<sub>2</sub>), prevalent in processed food, is less established. In this project, we investigated the impact of food grade TiO<sub>2</sub> on gut microbiota of mice when or ...[more]

PMID: 31165072

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Project description:Interventions: This study is a cross-over design, including only healthy volunteers. A cross-over design was chosen because it is the most appropriate design for this study: it will reduce the individual differences by allowing every subject to be his own control. This study will be done in 4 weeks and include 2 periods. The volunteers will be randomized in two groups: one group will start with the intervention period and the other one will start with the control period. After, these 2 weeks of intervention or control periods, the volunteers will start the control period and intervention period respectively for another 2 weeks. The time of exposure is 2 weeks. Indeed, it takes 5 to 7 days for the turnover of the epithelial cells in the gut. This will ensure the exposure of all the cells of the luminal surface of the colon. The control period, is meant to reduce to a minimum the ingestion of E171 in order to have all the volunteers to start the same level of E171. During this period the volunteers will receive a list of products to avoid like cookies, chewing gum, certain toothpaste that are known to contain a significant amount of E171. The intervention period, is meant to control the amount of E171 that the volunteers will ingest. A concentration, 0.82 mg/kg bw/day, corresponding to a normal daily consumption will be given to the volunteers. The quantity will be adjusted to the body weight and dispersed in yoghurt that will be eaten at breakfast, lunch and dinner. In order to verify the compliance of the subjects, once in every period the subjects will prepare a package that include exactly what they ate and drank all day. This food package will be mixed and tested for TiO2 content. Primary outcome(s): The primary outcome parameters are differences in transcriptomic markers after consumption of food additive E171. These outcomes in humans will shed light on the relevance of markers identified in preclinical studies, and how the animal data on the risk of facilitation of tumour growth can be extrapolated to humans Study Design: Randomized controlled trial, Single blinded (masking used), N/A , unknown, Crossover

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.

Dataset Information

Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

Publications

Impact of the Food Additive Titanium Dioxide (E171) on Gut Microbiota-Host Interaction.

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