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

• Published in: Journal of nanobiotechnology Vol. 16; no. 1; p. 53
• Main Authors: Talbot, Pauline, Radziwill-Bienkowska, Joanna M, Kamphuis, Jasper B. J, Steenkeste, Karine, Bettini, Sarah, Robert, Vnronique, Noordine, Marie-Louise, Mayeur, Camille, Gaultier, Eric, Langella, Philippe, Robbe-Masselot, Catherine, Houdeau, Eric, Thomas, Muriel, Mercier-Bonin, Muriel
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 19-06-2018; BioMed Central; BMC
• Subjects: Automation; Biotechnology; Cecum; Cell division; Chains; Confocal microscopy; Digestive system; E coli; Epithelial cells; Escherichia coli; Exposure; Fatty acids; Fluorescence; Food; Food additives; Food-grade TiO2; Gastrointestinal system; Gastrointestinal tract; Gene expression; Glycosylation; Gut barrier; Health aspects; Immunofluorescence; In vivo methods and tests; Intestinal mucosa; Intestine; Irradiation; Life Sciences; Microbiota; Microscopy; Mucin; Mucin O-glycans; Mucus; Nanomaterials; Nanoparticles; Physiological aspects; Pollutants; Rodents; Scanning microscopy; Short-chain fatty acids; Synthesis; Titanium dioxide; Trapping; Ultraviolet radiation; France; United States > US; Short-chain fatty acids; Mucus; Food-grade TiO2; Mucin O-glycans; Gut barrier
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-018-0379-5

Background Titanium dioxide (TiO2) particles are commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, the risk of gut barrier disruption is an increasing concern because of the presence of a nano-sized fraction. Food-grade E171 may interact with mucus, a gut barrier protagonist still poorly explored in food nanotoxicology. To test this hypothesis, a comprehensive approach was performed to evaluate in vitro and in vivo interactions between TiO2 and intestinal mucus, by comparing food-grade E171 with NM-105 (Aeroxyde P25) OECD reference nanomaterial. Results We tested E171-trapping properties of mucus in vitro using HT29-MTX intestinal epithelial cells. Time-lapse confocal laser scanning microscopy was performed without labeling to avoid modification of the particle surface. Near-UV irradiation of E171 TiO2 particles at 364 nm resulted in fluorescence emission in the visible range, with a maximum at 510 nm. The penetration of E171 TiO2 into the mucoid area of HT29-MTX cells was visualized in situ. One hour after exposure, TiO2 particles accumulated inside “patchy” regions 20 µm above the substratum. The structure of mucus produced by HT29-MTX cells was characterized by MUC5AC immunofluorescence staining. The mucus layer was thin and organized into regular “islands” located approximately 20 µm above the substratum. The region-specific trapping of food-grade TiO2 particles was attributed to this mucus patchy structure. We compared TiO2-mediated effects in vivo in rats after acute or sub-chronic oral daily administration of food-grade E171 and NM-105 at relevant exposure levels for humans. Cecal short-chain fatty acid profiles and gut mucin O-glycosylation patterns remained unchanged, irrespective of treatment. Conclusions Food-grade TiO2 is trapped by intestinal mucus in vitro but does not affect mucin O-glycosylation and short-chain fatty acid synthesis in vivo, suggesting the absence of a mucus barrier impairment under “healthy gut” conditions.