Transcriptomics effects of ingestion of food additive titanium dioxide (E171) in the colon of a chemically induced colorectal cancer model
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PROVIDER: PRJNA431295 | ENA |
REPOSITORIES: ENA
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Project description:Exposure to titanium dioxide (TiO2) food additive by ingestion increased over the years. TiO2 is used in food to give a brighter, fresher colour to sweets, cookies, salad dressing under the name E171. New studies on E171 showed that after ingestion in a colorectal cancer mouse model, a significant increased number of colorectal tumours were found. In addition, short-term exposure to E171 induces gene expression changes in relation to oxidative stress responses, an impairment of the immune system, activation of signalling and cancer-related genes. Furthermore, dysregulation of the immune system was also observed after ingestion of E171 in rats. E171 comprises nanoparticles (NPs) and microparticles (MPs). Previous in vitro studies showed the capacity of E171, TiO2 NPs and MPs to induce oxidative stress, DNA damage, and induction of the micronuclei. The aim of our study was to investigate the relative contribution of the NPs and MPs fractions to the effects of E171 at the molecular level. This investigation was performed using in vitro exposure of Caco-2 cells to E171 as well as the NPs and MPs fractions of TiO2 and assessing effects with genome wide gene expression analysis. Results showed that the E171, TiO2 NPs and MPs induce gene expression changes in signalling, inflammation, immune system, transport, and cancer. Contribution of NPs was observed on genes involved in TLR cascade, MHC class I and II presentation, late cornified envelope, potassium channels, and cell cycle. MPs contribution was observed with changes in gene expression on a target to Hedgehog family, α-defensins, cadherin and cholinergic receptors. The gene expression changes associated with the immune system and inflammation induced by E171, MPs, and NPs suggest the creation of a favourable environment for cancer development.
2019-11-22 | GSE110410 | GEO
Project description:Colorectal cancer is one of the most common cancers worldwide. Factors that could influence the increase or reduction of the risks, including dietary pattern, are under investigation. Previous studies showed the capacity of food additive titanium dioxide (E171) to induce DNA damage in vitro and facilitate growth of colorectal tumors in vivo. The aim of this study is to understand the molecular mechanisms behind these effects of E171 exposure. BALB/c mice were exposed by gavage to 5 mg/kgbw/day of E171 for 2, 7, 14 and 21 days. Transcriptome changes of the response to E171 exposure were studied by whole genome mRNA microarray analysis on the distal colons of the mice. The results showed significant changes in the transcriptome, mainly gene expression changes of the olfactory/GPCR receptor family, oxidative stress, immune responses and of cancer related genes. These pathways may represent the underlying molecular mechanisms by which E171 facilitates tumor formation in the colon of these mice.
2018-01-24 | GSE92563 | GEO
Project description:Titanium dioxide, a white colorant, is the mineral the most produced worldwide. It is used in food under the name of E171. Previous studies showed that in a chemically induced colorectal cancer mouse model, E171 increase significantly the number of tumours. The aim of this study was to understand the molecular mechanisms behind these effects of E171 exposure. BALB/c mice were exposed by gavage to 5 mg/kg bw/day of E171 for 2, 7, 14 and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.
2018-07-15 | GSE109520 | GEO
Project description:This study provides critical insights into the adverse effects of titanium dioxide (E171) on human gastrointestinal health and its potential molecular mechanisms of action, marking a significant advancement in food toxicology. Through a human dietary intervention study involving 31 participants consuming 2 mg/kg body weight/day of E171 in yogurt, the research confirmed compliance by detecting significantly elevated titanium levels in feces during the intervention. Importantly, the study identified a statistically significant increase in superoxide radicals in whole blood, indicating that E171 induces oxidative stress. While systemic inflammation markers, including cytokine levels and hs-CRP, showed no relevant changes, gene expression analysis of colon biopsies revealed substantial transcriptomic alterations. Specifically, 73 enriched pathways were identified, including those related to metabolic reprogramming (consistent with the Warburg effect), colorectal cancer development, ribosome biogenesis, PPAR signaling, and chemical carcinogenesis involving reactive oxygen species. Additionally, the characterization of E171's physicochemical properties post-gastrointestinal digestion provided a clearer understanding of nanoparticle exposure in the human gut. This study is novel as it delivers human-specific data, bridging a critical gap in the knowledge of E171’s health risks. It also provides molecular evidence linking its consumption to hallmarks of colorectal cancer. These findings support the European Union’s decision to ban E171 as a food additive and highlight its potential risks, contributing significantly to food toxicology.
2025-09-30 | E-MTAB-15089 | biostudies-arrayexpress
Project description:Microarrays after exposure in Caco-2 cells to titanium dioxide food additive E171 and titanium dioxide nanoparticles and microparticles
| PRJNA433654 | ENA
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
| 20119 | ecrin-mdr-crc
Project description:Food-grade titanium dioxide (E171) is a widely used food additive whose safety is debated, particularly concerning its genotoxic effects. This experiment describes E171-induced effects on iPSC-derived colon organoids and evaluates the dose-response to 10, 100, 250, and 1000 µg/mL of E171 following 24 hours of exposure. Whole genome RNA sequencing was performed to assess molecular mechanisms and effects of E171 on the gene expression of human iPSC-derived colon organoids to better understand the potential mode of action of its adverse effects.
2025-04-30 | E-MTAB-14778 | biostudies-arrayexpress
Project description:Titanium dioxide nanofiber (TDNF) is widely used in the manufacture of various household products including cosmetics. As a result, there is a possibility of negative impact on human health. The goal of the present study is to investigate the short-term effects of titanium dioxide nanofiber ingestion of male Sprague Dawley rats. TDNF was fabricated via electrospinning method, followed by dissolution in water. Six- to seven-week-old male Sprague Dawley rats were exposed to a total of 0, 40, and 60 ppm of TDNF for 2 weeks via oral gavage. Lungs and other tissues were autopsied and excised immediately frozen in liquid nitrogen and stored at -80 deg C until analysis. Total RNA was converted to single-stranded sense-target, fragmented, labeled, and hybridized to the Affymetrix Rat Gene ST 2.0 microarray according to the manufacturer’s protocol.
2023-08-31 | E-MTAB-13260 | biostudies-arrayexpress
Project description: Not available
| S-EPMC8101360 | biostudies-literature
Project description: Not available
| S-EPMC11295244 | biostudies-literature