Cytotoxicity of Nanoparticles Contained in Food on Intestinal Cells and the Gut Microbiota

Abstract

Toxicity of nanoparticles (NPs) upon oral exposure has been studied in animals using physiological changes, behavior, histology, and blood analysis for evaluation. The effects recorded include the combination of the action on cells of the exposed animal and the reaction of the microorganisms that populate the external and internal surfaces of the body. The importance of these microorganisms, collectively termed as microbiota, for the health of the host has been widely recognized. They may also influence toxicity of NPs but these effects are difficult to differentiate from toxicity on cells of the gastrointestinal tract. To estimate the likelihood of preferential damage of the microbiota by NPs the relative sensitivity of enterocytes and bacteria was compared. For this comparison NPs with antimicrobial action present in consumer products were chosen. The comparison of cytotoxicity with Escherichia coli as representative for intestinal bacteria and on gastrointestinal cells revealed that silver NPs damaged bacteria at lower concentrations than enterocytes, while the opposite was true for zinc oxide NPs. These results indicate that silver NPs may cause adverse effects by selectively affecting the gut microbiota. Fecal transplantation from NP-exposed animals to unexposed ones offers the possibility to verify this hypothesis.

Keywords: antimicrobial effects; cytotoxicity; nanotoxicology; silver; zinc oxide.

Figure 1

Uptake of NPs by mammalian cells (A) and by bacteria (B). (A) NPs can cross the plasma membrane by diffusion (1), endocytotic uptake (2, 3), and disruption of membrane integrity (4). Endocytosis can occur either by invagination of the membrane (clathrin, caveolin, clathrin- and caveolin-independent routes, 2) or by evagination (macropinocytosis, 3); (B) NPs permeate the bacterial wall of gram-negative bacteria, consisting of an inner membrane, a peptidoglycan layer and an outer membrane, and the wall of gram-positive bacteria (membrane + several peptidoglycan layers) by membrane disruption. Membrane proteins are indicated in different colors in the bacterial cell membrane but were not shown in the mammalian plasma membrane.

Figure 2

Effects of Ag and ZnO NPs in eukaryotic (A) versus prokaryotic (B) cells with mechanisms (ROS generation, action of Ag and Zn ions) indicated by different colors. NPs may enter mammalian cells either by endosomal uptake or by diffusion. For bacterial cells, the only uptake mechanism is diffusion across the bacterial wall. Target organelles for NP effects, such as mitochondria, lysosomes and nucleus, are indicated. Ribosomes are essential components of mammalian and bacterial cells; they are in a similar size range as NPs. ROS, reactive oxygen species.