Oral exposure to Ag or TiO2 nanoparticles perturbed gut transcriptome and microbiota in a mouse model of ulcerative colitis

Food Chem Toxicol. 2022 Nov:169:113368. doi: 10.1016/j.fct.2022.113368. Epub 2022 Sep 7.

Abstract

Silver (nAg) and titanium dioxide (nTiO2) nanoparticles improve texture, flavour or anti-microbial properties of various food products and packaging materials. Despite their increased oral exposure, their potential toxicities in the dysfunctional intestine are unclear. Here, the effects of ingested nAg or nTiO2 on inflamed colon were revealed in a mouse model of chemical-induced acute ulcerative colitis. Mice (eight/group) were exposed to nAg or nTiO2 by oral gavage for 10 consecutive days. We characterized disease phenotypes, histology, and alterations in colonic transcriptome (RNA sequencing) and gut microbiome (16S sequencing). Oral exposure to nAg caused only minor changes in phenotypic hallmarks of colitic mice but induced extensive responses in gene expression enriching processes of apoptotic cell death and RNA metabolism. Instead, ingested nTiO2 yielded shorter colon, aggravated epithelial hyperplasia and deeper infiltration of inflammatory cells. Both nanoparticles significantly changed the gut microbiota composition, resulting in loss of diversity and increase of potential pathobionts. They also increased colonic mucus and abundance of Akkermansia muciniphila. Overall, nAg and nTiO2 induce dissimilar immunotoxicological changes at the molecular and microbiome level in the context of colon inflammation. The results provide valuable information for evaluation of utilizing metallic nanoparticles in food products for the vulnerable population.

Keywords: 16S sequencing; DSS-Induced colitis; Gut microbiota; Inflammation; Metal oxides; Mouse model; Nanoparticles; RSEQ.

MeSH terms

  • Animals
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / metabolism
  • Colon* / drug effects
  • Colon* / microbiology
  • Dextran Sulfate
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Metal Nanoparticles* / toxicity
  • Mice
  • Mice, Inbred C57BL
  • RNA / metabolism
  • Silver* / toxicity
  • Titanium* / toxicity
  • Transcriptome

Substances

  • Dextran Sulfate
  • RNA
  • Silver
  • Titanium
  • titanium dioxide