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

Abstract

Background: In food toxicology, there is growing interest in studying the impacts of foodborne nanoparticles (NPs, originating from food additives, food supplements or food packaging) on the intestinal microbiome due to the important and complex physiological roles of these microbial communities in host health. Biocidal activities, as described over recent years for most inorganic and metal NPs, could favour chronic changes in the composition and/or metabolic activities of commensal bacteria (namely, intestinal dysbiosis) with consequences on immune functions. Reciprocally, direct interactions of NPs with the immune system (e.g., inflammatory responses, adjuvant or immunosuppressive properties) may in turn have effects on the gut microbiota. Many chronic diseases in humans are associated with alterations along the microbiota-immune system axis, such as inflammatory bowel diseases (IBD) (Crohn's disease and ulcerative colitis), metabolic disorders (e.g., obesity) or colorectal cancer (CRC). This raises the question of whether chronic dietary exposure to inorganic NPs may be viewed as a risk factor facilitating disease onset and/or progression. Deciphering the variety of effects along the microbiota-immune axis may aid the understanding of how daily exposure to inorganic NPs through various foodstuffs may potentially disturb the intricate dialogue between gut commensals and immunity, hence increasing the vulnerability of the host. In animal studies, dose levels and durations of oral treatment are key factors for mimicking exposure conditions to which humans are or may be exposed through the diet on a daily basis, and are needed for hazard identification and risk assessment of foodborne NPs. This review summarizes relevant studies to support the development of predictive toxicological models that account for the gut microbiota-immune axis.

Conclusions: The literature indicates that, in addition to evoking immune dysfunctions in the gut, inorganic NPs exhibit a moderate to extensive impact on intestinal microbiota composition and activity, highlighting a recurrent signature that favours colonization of the intestine by pathobionts at the expense of beneficial bacterial strains, as observed in IBD, CRC and obesity. Considering the long-term exposure via food, the effects of NPs on the gut microbiome should be considered in human health risk assessment, especially when a nanomaterial exhibits antimicrobial properties.

Keywords: Colorectal cancer; Gut dysbiosis; Gut inflammation; Intestinal microbiota; Nanoparticles; Obesity; Silicon dioxide; Silver; Titanium dioxide; Zinc oxide.

Fig. 1

The gut microbiota modulates the intestinal immune response. The gut microbiota influences the development of T cell subsets, intraepithelial lymphocytes (IELs) and are critical for the induction of plasma cells which produce immunoglobulin A (IgA). Dendritic cells (DCs) sample microbial antigens that pass through the epithelial barrier via microfold (M) cells or capture antigens from the lumen directly by extending dendrites between the intestinal epithelial cells. Some of these DCs migrate to the mesenteric lymph nodes and induce naïve T cells differentiation into regulatory T-cell (Treg) by production of transforming growth factor β (TGF-β) and retinoic acid. Segmented filamentous bacteria (SFB) exhibit pro-inflammatory effects by inducing IL-17 and IgA production, whereas Bacteroides fragilis, Faecalibacterium prausnitzii and short-chain fatty acids (SCFAs) exhibit anti-inflammatory effects via recruitment of Treg that produce the immunosuppressive cytokine IL-10. The intestinal flora also regulates immune response by the production of aryl hydrocarbon receptor (AhR) ligands able to activate AhR, highly expressed on IELs, Th17, Th22, innate lymphoid cells group 3 (ILC3) that produce IL-17 and/or IL-22. These cytokines induce secretion of antimicrobial peptides (AMPs) from Paneth cells and intestinal epithelial cells. AMPs shape the microbiota and are also involved in colonization resistance against pathogens

Fig. 2

Potential impact of NP ingestion on the crosstalk between the microbiota and the immune system. After ingestion, NPs interact with the gastrointestinal environment and can alter the gut microbiota, characterized by an alteration of the F/B ratio, a depletion of Lactobacillus strains and an increase in the abundance of Proteobacteria. NPs exhibit also deleterious effects on the epithelial barrier and the intestinal immune response, which can amplifies the dysbiosis in a vicious circle favouring intestinal inflammation in susceptible individuals