The growing use of nanoparticles (NPs) — clusters of atoms ranging from 1 to 100 nanometers (one millimeter equals one million nanometers) in one dimension— in the food chain, as additives or incorporated into food packaging, has led to concern over their impact on human health. Recent reviews have reported that the gut microbiota may be adversely altered by NPs, leading to shifts resembling that in diseases where gut dysbiosis plays a key pathogenic role.
Nanoparticles, in brief
Particles with sizes in the nanoscale range present unique physical and chemical properties due to their high surface area-to-volume ratio that makes them suitable for applications in various industries. Nanoparticles are widely used in everyday consumer products such as foodstuffs, healthcare, clothing, sunscreens, and cosmetics, and may enter consumer products unintentionally as contaminants, thus human exposure is nearly unavoidable. A 2015 report cited 1814 products (representing 622 companies and 32 countries) containing nanomaterials and 117 of them fit under the “food and beverage” category.
Though inhalation and skin absorption are more studied routes, oral ingestion via food additives and packaging are also of concern.
Among inorganic NPs, titanium dioxide (TiO2), silver (Ag), and silicon dioxide (SiO2) are commonly used as food coloring or anti-caking agents, while others are added as food supplements, such as zinc oxide (ZnO).
Nanoparticles interact with the gut environment
NPs have been shown to impact the mucus layer, mucus-producing cells, and intestinal epithelial cells, barriers that protect the host from pathogens; their disruption can lead to gut dysbiosis. 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 the systemic circulation.
Changes in the physicochemical properties of NPs during gut transit (i.e., differences in pH and influence of the food matrices and biliary acids) or the extent of particle dissolution for soluble materials (i.e., Ag, ZnO), could modify their long-term impact on the microbiome. As for insoluble particles (e.g., TiO2, SiO2) their limited absorption can extend the contact time with resident bacteria.
Nanoparticles effect on gut microbiota
Inorganic NPs have the potential to alter the intestinal microbiota and the gut-associated lymphoid tissue (immune cells), interactions of which are important for many physiological processes.
A 2020 review found that existing data highlight a recurrent microbiota signature for nanoparticles Ag, TiO2, ZnO, and SiO2 characterized by:
- Alteration of the Firmicutes/Bacteroidetes (F/B) ratio
- Depletion of lactobacilli and bifidobacteria (SCFA producers)
- Increase in the abundance of Proteobacteria
- Deleterious effects on the epithelial barrier and the intestinal immune response
The studies used in the review are described in Table 1 (animal models), Table 2 (humans), Table 3 (in vitro studies on immunological properties of NPs), and Table 4 (the modulation of the immune response in vivo which may, in turn, modulate the microbiota).
In addition, a 2022 systematic review with a total of 46 in vivo and 22 in vitro studies of the effect of NPS on gut microbiota found that most studies indicated adverse effects of nanoparticles on gut microbiota.
Disease states resembling nanoparticle exposure
Alterations along the microbiota-immune system axis are associated with many diseases, such as inflammatory bowel diseases, metabolic disorders, colorectal cancer, and neurodevelopmental disorders.
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.
There is evidence that the NP-induced gut microbiota signature resembles that of dysbiosis-associated human diseases.
Despite some contradictory studies, the majority of observations in the previously mentioned 2020 review found that the nanoparticles Ag, TiO2, ZnO, and SiO2 were associated with a microbiota signature characterized by alteration of the F/B ratio together with the depletion of Lactobacillus and enrichment of Proteobacteria.
- Firmicutes/Bacteroidetes (F/B ratio) is particularly indicative of the overall health of the gut microbiota. Its alteration has been observed in diseases associated with dysbiosis and helps to predict the decrease in the relative abundance of SCFAs.
- Decreased abundances in the levels of SCFA-producing bacteria in the microbiota of patients, namely, Faecalibacterium, Roseburia, and Bifidobacterium,as well as lactobacilli, was observed in IBD and obese patients, while similar depletion appears in rodents orally exposed to TiO2, Ag, SiO2 and ZnO NPs.
- Increase in the abundance of Proteobacteria, which may resemble the microbiome shift in inflammatory bowel disease, colorectal cancer, or obesity where gut dysbiosis plays a key pathogenic role.
- In addition, NPs exhibit deleterious effects on the epithelial barrier and the intestinal immune response, which can amplify the dysbiosis in a vicious circle favoring intestinal inflammation in susceptible individuals.
Ultimately, NP consumption through food can alter the composition of the gut microbiota towards disease-prone states, potentially promoting pathogenesis and contributing to various autoimmune and gut-related diseases.
Given the ubiquity of NPs in the food supply, further studies in this vein are warranted, as emphasized in a guidance document from the European Food Safety Authority based on the risk assessment of nanotechnology applications in the food and feed chain.
In addition to evoking immune dysfunctions in the gut, inorganic NPs alter microbiota composition and activity, highlighting a recurrent dysbiotic signature at the expense of beneficial bacterial strains. Similar alterations are observed in diseases such as inflammatory bowel disease, colorectal cancer, 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.
By Clare Fleishman MS RDN & Editor Arthur Ouwehand PhD
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