H. Shi, R. Magaye, V. Castranova, and J. Zhao, Titanium dioxide nanoparticles: a review of current toxicological data, Part. Fibre Toxicol, issue.10, p.15, 2013.

, European Commission, Recommendation on the definition of a nanomaterial, Official Journal of the European Union, 2011.

M. Dorier, D. Beal, C. Marie-desvergne, M. Dubosson, F. Barreau et al., Continuous in vitro exposure of intestinal epithelial cells to E171 food additive causes oxidative stress, inducing oxidation of DNA bases but no endoplasmic reticulum stress, Nanotoxicology, vol.11, pp.751-761, 2017.
URL : https://hal.archives-ouvertes.fr/cea-01564506

J. J. Faust, K. Doudrick, Y. Yang, P. Westerhoff, and D. G. Capco, Food grade titanium dioxide disrupts intestinal brush border microvilli in vitro independent of sedimentation, Cell Biol. Toxicol, vol.30, pp.169-188, 2014.

A. Weir, P. Westerhoff, L. Fabricius, K. Hristovski, and N. Goetz, Titanium dioxide nanoparticles in food and personal care products, Environ. Sci. Technol, vol.46, pp.2242-2250, 2012.

K. Yang, X. Doudrick, K. Bi, P. Hristovski, P. Herckes et al., Characterization of food-grade titanium dioxide: the presence of nanosized particles, Environ. Sci. Technol, vol.48, pp.6391-6400, 2014.

H. Bouwmeester, M. Van-der-zande, and M. A. Jepson, Effects of food-borne nanomaterials on gastrointestinal tissues and microbiota, Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol, vol.10, 2018.

A. Efsa and . Panel, Scientific Opinion on the re-evaluation of titanium dioxide (E 171) as a food additive, EFSA J, vol.14, pp.4545-4628, 2016.

C. Rompelberg, M. B. Heringa, G. Van-donkersgoed, J. Drijvers, A. Roos et al., Oral intake of added titanium dioxide and its nanofraction from food products, food supplements and toothpaste by the Dutch population, Nanotoxicology, vol.10, pp.1404-1414, 2016.

D. B. Warheit, R. Boatman, and S. C. Brown, Developmental toxicity studies with 6 forms of titanium dioxide test materials (3 pigment-different grade & 3 nanoscale) demonstrate an absence of effects in orally-exposed rats, Regul. Toxicol. Pharmacol, vol.73, pp.887-896, 2015.

D. B. Warheit, S. C. Brown, and E. M. Donner, Acute and subchronic oral toxicity studies in rats with nanoscale and pigment grade titanium dioxide particles, Food Chem. Toxicol, vol.84, pp.208-224, 2015.

D. B. Warheit and E. M. Donner, Risk assessment strategies for nanoscale and fine-sized titanium dioxide particles: Recognizing hazard and exposure issues, Food Chem. Toxicol, vol.85, pp.138-147, 2015.

I. M. Urrutia-ortega, L. G. Garduno-balderas, N. L. Delgadobuenrostro, V. Freyre-fonseca, J. O. Flores-flores et al., Food-grade titanium dioxide exposure exacerbates tumor formation in colitis associated cancer model, Food Chem. Toxicol, vol.93, pp.20-31, 2016.

S. Bettini, E. Boutet-robinet, C. Cartier, C. Comera, E. Gaultier et al., Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon, vol.7, p.40373, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01508951

H. Proquin, M. J. Jetten, M. C. Jonkhout, L. G. Gardunobalderas, J. J. Briede et al., Gene expression profiling in colon of mice exposed to food additive titanium dioxide (E171), Food Chem. Toxicol, vol.111, pp.153-165, 2018.

H. Proquin, C. Rodriguez-ibarra, C. G. Moonen, I. M. Ortega, J. J. Briede et al., Titanium dioxide food additive (E171) induces ROS formation and genotoxicity: contribution of micro and nanosized fractions, Mutagenesis, vol.32, pp.139-149, 2017.

F. Sommer and F. Backhed, The gut microbiota -masters of host development and physiology, Nat. Rev. Microbiol, issue.11, pp.227-238, 2013.

M. A. Mcguckin, S. K. Linden, P. Sutton, and T. H. Florin, Mucin dynamics and enteric pathogens, Nat. Rev. Microbiol, vol.9, pp.265-278, 2011.

K. R. Groschwitz and S. P. Hogan, Intestinal barrier function: molecular regulation and disease pathogenesis, J. Allergy Clin. Immunol, vol.124, pp.3-20, 2009.

E. M. Leslie, R. G. Deeley, and S. P. Cole, Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense, Toxicol. Appl. Pharmacol, vol.204, pp.216-237, 2005.

A. M. Mowat, Anatomical basis of tolerance and immunity to intestinal antigens, Nat. Rev. Immunol, vol.3, pp.331-341, 2003.

L. Antoni, S. Nuding, J. Wehkamp, and E. F. Stange, Intestinal barrier in inflammatory bowel disease, World J. Gastroenterol, vol.20, pp.1165-1179, 2014.

A. N. Ananthakrishnan, Epidemiology and risk factors for IBD, Nat. Rev. Gastroenterol. Hepatol, vol.12, pp.205-217, 2015.

M. C. Lomer, R. P. Thompson, and J. J. Powell, Fine and ultrafine particles of the diet: influence on the mucosal immune response and association with Crohn's disease, Proc. Nutr. Soc, vol.61, pp.123-130, 2002.

E. Brun, F. Barreau, G. Veronesi, B. Fayard, S. Sorieul et al., Titanium dioxide nanoparticle impact and translocation through ex vivo, in vivo and in vitro gut epithelia, Part. Fibre Toxicol, p.13, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-00971511

C. Gitrowski, A. R. Al-jubory, and R. D. Handy, Uptake of different crystal structures of TiO2 nanoparticles by Caco-2 intestinal cells, Toxicol. Lett, vol.226, pp.264-276, 2014.

E. Y. Chen, M. Garnica, Y. C. Wang, C. S. Chen, and W. C. Chin, Mucin secretion induced by titanium dioxide nanoparticles, PLoS One, 2011.

P. Talbot, J. M. Radziwill-bienkowska, J. B. Kamphuis, K. Steenkeste, S. Bettini et al., Food-grade TiO2 is trapped by intestinal mucus in vitro but does not impair mucin O-glycosylation and short-chain fatty acid synthesis in vivo: implications for gut barrier protection, J. Nanobiotechnol, p.53, 2018.

T. Waller, C. Chen, and S. L. Walker, Food and Industrial Grade Titanium Dioxide Impacts Gut Microbiota, Environ. Eng. Sci, vol.34, pp.537-550, 2017.

H. Q. Chen, R. F. Zhao, B. Wang, C. X. Cai, L. N. Zheng et al., The effects of orally administered Ag, TiO2 and SiO2 nanoparticles on gut microbiota composition and colitis induction in mice, vol.8, pp.80-88, 2017.

W. Dudefroi, K. Moniz, E. Allen-vercoe, M. H. Ropers, and V. K. Walker, Impact of food grade and nano-TiO2 particles on a human intestinal community, Food Chem. Toxicol, vol.106, pp.242-249, 2017.

B. C. Schanen, A. S. Karakoti, S. Seal, D. R. Drake, W. L. Warren et al., Exposure to Titanium Dioxide Nanomaterials Provokes Inflammation of an in Vitro Human Immune Construct, ACS Nano, vol.3, pp.2523-2532, 2009.

M. Giovanni, J. Q. Yue, L. F. Zhang, J. P. Xie, C. N. Ong et al., Pro-inflammatory responses of RAW264.7 macrophages when treated with ultralow concentrations of silver, titanium dioxide, and zinc oxide nanoparticles, J. Hazard. Mater, vol.297, pp.146-152, 2015.

C. Y. Tay, W. Fang, M. I. Setyawati, S. L. Chia, K. S. Tan et al., Nano-hydroxyapatite and nanotitanium dioxide exhibit different subcellular distribution and apoptotic profile in human oral epithelium, ACS Appl. Mater. Interfaces, vol.6, pp.6248-6256, 2014.

T. Lesuffleur, A. Barbat, E. Dussaulx, and A. Zweibaum, Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus-secreting cells, Cancer Res, vol.50, pp.6334-6343, 1990.

E. Walter, S. Janich, B. J. Roessler, J. M. Hilfinger, and G. L. Amidon, HT29-MTX/Caco-2 cocultures as an in vitro model for the intestinal epithelium: In vitro in vivo correlation with permeability data from rats and humans, J. Pharm. Sci, vol.85, pp.1070-1076, 1996.

A. Efsa and . Panel, Re-evaluation of titanium dioxide (E171) as a food additive, EFSA J, vol.14, pp.4545-4628, 2016.

B. Pignon, H. Maskrot, V. G. Ferreol, Y. Leconte, S. Coste et al.,

. Boime, Versatility of laser pyrolysis applied to the synthesis of TiO2 nanoparticles -Application to UV attenuation, Eur. J. Inorg. Chem, pp.883-889, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00179674

M. Dorier, E. Brun, G. Veronesi, F. Barreau, K. Pernet-gallay et al., Impact of anatase and rutile titanium dioxide nanoparticles on uptake carriers and efflux pumps in Caco-2 gut epithelial cells, Nanoscale, vol.7, pp.7352-7360, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01157522

J. F. Forstner and G. G. Forstner, Physiology of the gastrointestinal tract, pp.1255-1283, 1994.

M. W. Pfaffl, A. Tichopad, C. Prgomet, and T. P. Neuvians, Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeperExcel-based tool using pair-wise correlations, Biotechnol. Lett, vol.26, pp.509-515, 2004.

M. W. Pfaffl, G. W. Horgan, and L. Dempfle, Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in realtime PCR, Nucleic Acids Res, 2002.

B. S. Harvey, T. C. Sia, D. A. Wattchow, and S. D. Smid, Interleukin 17A evoked mucosal damage is attenuated by cannabidiol and anandamide in a human colonic explant model, Cytokine+, vol.65, pp.236-244, 2014.

D. Wei, M. Kanai, S. Huang, and K. Xie, Emerging role of KLF4 in human gastrointestinal cancer, Carcinogenesis, vol.27, pp.23-31, 2006.

M. G. Smirnova, L. Guo, J. P. Birchall, and J. P. Pearson, LPS up-regulates mucin and cytokine mRNA expression and stimulates mucin and cytokine secretion in goblet cells, Cell. Immunol, vol.221, pp.42-49, 2003.

T. Hosoi, R. Hirose, S. Saegusa, A. Ametani, K. Kiuchi et al., Cytokine responses of human intestinal epithelial-like Caco-2 cells to the nonpathogenic bacterium Bacillus subtilis (natto), Int. J. Food Microbiol, vol.82, pp.255-264, 2003.

C. Rodriguez-juan, M. Perez-blas, A. P. Valeri, N. Aguilera, A. Arnaiz-villena et al., Cell surface phenotype and cytokine secretion in Caco-2 cell cultures: increased RANTES production and IL-2 transcription upon stimulation with IL-1beta, Tissue Cell, vol.33, pp.570-579, 2001.

M. Akdis, S. Burgler, R. Crameri, T. Eiwegger, H. Fujita et al., Akdis, Interleukins, from 1 to 37, and interferon-gamma: receptors, functions, and roles in diseases, J. Allergy Clin. Immunol, vol.127, pp.701-721, 2011.

S. Bogaert, D. Laukens, H. Peeters, L. Melis, K. Olievier et al., Differential mucosal expression of Th17-related genes between the inflamed colon and ileum of patients with inflammatory bowel disease, BMC Immunol, p.61, 2010.

E. A. Garcia-zepeda, M. E. Rothenberg, R. T. Ownbey, J. Celestin, P. Leder et al., Human eotaxin is a specific chemoattractant for eosinophil cells and provides a new mechanism to explain tissue eosinophilia, Nat. Med, vol.2, pp.449-456, 1996.

C. Monteiller, L. Tran, W. Macnee, S. Faux, A. Jones et al., The pro-inflammatory effects of low-toxicity low-solubility particles, nanoparticles and fine particles, on epithelial cells in vitro: the role of surface area, Occup. Environ. Med, vol.64, pp.609-615, 2007.

T. E. Abbott-chalew and K. J. Schwab, Toxicity of commercially available engineered nanoparticles to Caco-2 and SW480 human intestinal epithelial cells, Cell Biol. Toxicol, vol.29, pp.101-116, 2013.

I. De-angelis, F. Barone, A. Zijno, L. Bizzarri, M. T. Russo et al., Comparative study of ZnO and TiO2 nanoparticles: physicochemical characterisation and toxicological effects on human colon carcinoma cells, Nanotoxicology, issue.7, pp.1361-1372, 2013.

K. Gerloff, D. I. Pereira, N. Faria, A. W. Boots, J. Kolling et al., Influence of simulated gastrointestinal conditions on particle-induced cytotoxicity and interleukin-8 regulation in differentiated and undifferentiated Caco-2 cells, Nanotoxicology, issue.7, pp.353-366, 2013.

R. M. Fusaro and R. W. Goltz, A comparative study of the periodic acid-Schiff and alcian blue stains, J. Invest. Dermatol, vol.35, pp.305-307, 1960.

R. Bansil and B. S. Turner, The biology of mucus: Composition, synthesis and organization, Adv. Drug Delivery Rev, vol.124, pp.3-15, 2018.

M. A. Mcguckin, R. Eri, L. A. Simms, T. H. Florin, and G. Radford-smith, Intestinal barrier dysfunction in inflammatory bowel diseases, vol.15, pp.100-113, 2009.

M. E. Johansson, D. Ambort, T. Pelaseyed, A. Schutte, J. K. Gustafsson et al., Composition and functional role of the mucus layers in the intestine, Cell. Mol. Life Sci, vol.68, pp.3635-3641, 2011.

H. Clevers, Wnt/beta-catenin signaling in development and disease, Cell, vol.127, pp.469-480, 2006.

C. G. Dietrich, A. Geier, and R. Elferink, ABC of oral bioavailability: transporters as gatekeepers in the gut, Gut, vol.52, pp.1788-1795, 2003.

H. Clevers, The intestinal crypt, a prototype stem cell compartment, Cell, vol.154, pp.274-284, 2013.

C. Crosnier, D. Stamataki, and J. Lewis, Organizing cell renewal in the intestine: stem cells, signals and combinatorial control, Nat. Rev. Genet, vol.7, pp.349-359, 2006.

E. C. Cho, Q. Zhang, and Y. Xia, The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles, Nat. Nanotechnol, vol.6, pp.385-391, 2011.

J. W. Richter, G. M. Shull, J. H. Fountain, Z. Guo, L. P. Musselman et al., Titanium dioxide nanoparticle exposure alters metabolic homeostasis in a cell culture model of the intestinal epithelium and Drosophila melanogaster, Nanotoxicology, vol.12, pp.390-406, 2018.

Z. M. Song, N. Chen, J. H. Liu, H. Tang, X. Deng et al., Biological effect of food additive titanium dioxide nanoparticles on intestine: an in vitro study, J. Appl. Toxicol, vol.35, pp.1169-1178, 2015.