Toxicity of Food-Grade TiO2 to Commensal Intestinal and Transient Food-Borne Bacteria: New Insights Using Nano-SIMS and Synchrotron UV Fluorescence Imaging

Abstract

Titanium dioxide (TiO2) is commonly used as a food additive (E171 in the EU) for its whitening and opacifying properties. However, a risk of intestinal barrier disruption, including dysbiosis of the gut microbiota, is increasingly suspected because of the presence of a nano-sized fraction in this additive. We hypothesized that food-grade E171 and Aeroxyde P25 (identical to the NM-105 OECD reference nanomaterial in the European Union Joint Research Centre) interact with both commensal intestinal bacteria and transient food-borne bacteria under non-UV-irradiated conditions. Based on differences in their physicochemical properties, we expect a difference in their respective effects. To test these hypotheses, we chose a panel of eight Gram-positive/Gram-negative bacterial strains, isolated from different biotopes and belonging to the species Escherichia coli, Lactobacillus rhamnosus, Lactococcus lactis (subsp. lactis and cremoris), Streptococcus thermophilus, and Lactobacillus sakei. Bacterial cells were exposed to food-grade E171 vs. P25 in vitro and the interactions were explored with innovative (nano)imaging methods. The ability of bacteria to trap TiO2 was demonstrated using synchrotron UV fluorescence imaging with single cell resolution. Subsequent alterations in the growth profiles were shown, notably for the transient food-borne L. lactis and the commensal intestinal E. coli in contact with food-grade TiO2. However, for both species, the reduction in cell cultivability remained moderate, and the morphological and ultrastructural damages, observed with electron microscopy, were restricted to a small number of cells. E. coli exposed to food-grade TiO2 showed some internalization of TiO2 (7% of cells), observed with high-resolution nano-secondary ion mass spectrometry (Nano-SIMS) chemical imaging. Taken together, these data show that E171 may be trapped by commensal and transient food-borne bacteria within the gut. In return, it may induce some physiological alterations in the most sensitive species, with a putative impact on gut microbiota composition and functioning, especially after chronic exposure.

Repurposing a platelet aggregation inhibitor ticagrelor as an antimicrobial against Clostridioides difficile

“…6). These observations are similar to those of bacteria exposed to TiO 2 , which reportedly causes bacterial cell rupture 18 . However, the exact mechanism how ticagrelor kills C. difficile remains to be further explored.…”

The Nano–Intestine Interaction: Understanding the Location‐Oriented Effects of Engineered Nanomaterials in the Intestine

“…Commonly used nanomaterials, such as TiO 2 NMs, can also change the composition and metabolic activity of micro biota in coculture system of TiO 2 NMs (22 nm) and eight bacterial strains including both Grampositive and Gram negative bacteria. [117] Specifically, TiO 2 NMs increased the ratio of Lawsonia and Hyphomicrobium at genus level. Correlation analysis demonstrated that Lawsonia was associated with the generation of ROS while Hyphomicrobium showed an oppo site effect on that, indicating that nanomaterials can trigger oxidative stress through modulating the structure of gut microbiota.…”

Impacts of foodborne inorganic nanoparticles on the gut microbiota-immune axis: potential consequences for host health

“…Nevertheless, oral bioavailability studies in rodents and humans clearly showed very limited systemic absorption of TiO 2 (0.1 to 0.6% of the initial dose, respectively) [118,119]. This finding indicates that at least 99% of the ingested TiO 2 matter accumulates in the lumen of the gut with the commensals in permanent contact with the particles, especially due to repeated exposure, with the potential for alterations in the growth profiles of bacteria as shown in vitro for E171 [8]. Mice exposed for one week to TiO 2 -NPs at a relevant dose for humans (2.5 mg/kg bw/d) did not reveal any changes in the faecal microbiota composition [107].…”

“…Following ingestion, NPs interact with a complex gastrointestinal (GI) environment. The non-absorbed fractions of foodborne mineral NPs (or their ionic forms for soluble compounds, such as Ag and ZnO) are accumulated in the intestinal lumen as a result of daily consumption, and can directly interact with the intestinal microbiota colonizing the gut lumen as well as the mucus layer lining the epithelial surface [7][8][9]. A portion of the NPs then translocate through the epithelial barrier and are possibly captured by the intestinal immune cells (e.g., macrophages and dendritic cells), before reaching systemic circulation.…”