| Version | Summary | Created by | Modification | Content Size | Created at | Operation |
|---|---|---|---|---|---|---|
| 1 | Merry Ghebretatios | + 952 word(s) | 952 | 2021-03-04 04:43:59 | | | |
| 2 | Karina Chen | -5 word(s) | 947 | 2021-03-11 03:06:50 | | | | |
| 3 | Karina Chen | -5 word(s) | 947 | 2021-03-11 03:07:32 | | |
Nanoparticles (NPs) are clusters of atoms in the nano-scale. The use of inorganic NPs has expanded into various industries including food manufacturing, agriculture, cosmetics, and construction. This has allowed NPs access to the human gastrointestinal tract, yet little is known about their impact on human health. As the gut microbiome continues to be increasingly implicated in various gut diseases of unknown etiology, researchers have begun studying the potentially toxic effects of NPs on the gut microbiome and gut barrier. This research has been invaluable in determining the impact of NPs on the intestinal tract ultimately showing that NPs have the potential to contribute to diseases including inflammatory bowel disease and colorectal cancer. With a focus on inorganic nanoparticles, this review presents a discussion of these studies while highlighting NP characteristics, study design, and techniques. Additionally, NP-induced changes to microbial composition are compared with disease-associated alterations in order to elucidate a potential link.
Human exposure to NPs, clusters of atoms ranging from 1 to 100 nm in one dimension, is nearly unavoidable [1]. As of March 2015, there were 1814 products (representing 622 companies and 32 countries) containing nanomaterials and 117 of them fit under the “food and beverage” category [2]. Of these 117 products, 47% were advertised as having at least one nanomaterial while 62 of these products were composed of more than one nanomaterial. The products were grouped into five categories based on nanomaterial type and 37% fit under “metals” and “metal oxide nanoparticles”. TiO2, SiO2, and ZnO were the most produced nanomaterials by mass, worldwide, and Ag NPs made up 24% of the most popularly advertised nanomaterials. It is estimated that children consume 1.6–3.5 ug/kg body weight per day (bw/day) and adults consume 1.3–2.7 μg/kg bw/day of Ag NPs [1]. Humans consume an estimated 1.8 mg/kg bw/day of SiO2 NPs from food [3]. E171 food additives containing up to 43% TiO2 NPs have been used since 1969 in many food products, including chewing gum [4]. It is estimated that exposure to TiO2 NPs is 0.2–0.4 mg/kg bw for infants and the elderly, and 5.5–10.4 mg/kg bw for children [4]. Other studies suggest intake may be much higher due to the increased use of NPs in a variety of industries in addition to the food industry [2].
The nano-scale size of NPs affords them unique physicochemical properties that make them suitable for applications in various industries [5]. Inorganic NPs are widely used for processing, packaging, and nutrition [6]. TiO2 has been used as a coloring agent and enhancer for dairy products, beverages, seeds, processed foods, toothpaste, and even medications [7]. It is also used in coating candies [1]. SiO2 is registered within the EU as a food additive (E551) for maintaining flow in powder products and carrying flavors in food [6]. Ag NPs are used in food packaging as they have diverse antibacterial properties [8]. These antimicrobial NPs enter bacterial cells and interfere with respiration, phosphate uptake, DNA replication, and protein modifications [9]. Finally, ZnO NPs are used in antimicrobial food packaging and supplements among other applications [10][11].
NPs also have vast applications in fields outside of the food industry. For example, 12% of cosmetic products are advertised to have Ag and TiO2 NPs [2]. Similarly, Ag NPs are used as coatings for computer keyboards to protect against microbes [2]. Such wide-ranging applications of nanomaterials in various industries, allows for greater human exposure. This widespread application of nanotechnology likely increases direct human ingestion of these NPs providing them better access to the host gut microbiota through the GIT [6]. Indeed, research has shown that Ag NPs accumulate in the stomach, duodenum, ileum, jejunum, and colon [6]. TiO2 NPs were also found stored in the stomach and colon, while SiO2 NPs have been shown to be distributed in the stomach, ileum, and colon. This has caused understandable concern over the potential negative impact of NPs on the gut microbiome and the resulting effect on human health.
To be able to assess the risk associated with exposure to NPs, their stability in the GI lumen and their method of absorption must be well understood. Data shows that the stability, aggregation, and surface properties of NPs can change depending on their interactions with the GIT [12]. For instance, physical forces (peristalsis), osmotic concentration, pH, digestive enzymes, the presence of other foods, endogenous biochemicals, and commensal microbes may have an impact on NP characteristics. In turn, any changes to the NP will influence its absorption and how it may affect the gut microbiome. Cellular uptake of NPs may be endocytosis-dependent or endocytosis-independent [5]. Researchers suggest that the mechanism is influenced by the presence of microvilli as endocytosis of NPs is reduced in cells with extensive microvilli [5]. NPs were shown to pass between epithelial cells of the GIT by paracellular transport which involves disrupting the tight junctions that hold epithelial cells together. In other cases, goblet and M-cells can readily take in NPs through endocytosis. One study assessed the impact of NP size and agglomeration state on the levels and mechanisms of NP internalization [13]. It was found that well-dispersed silica NPs entered cells by Caveolae-mediated endocytosis whereas an increase in the agglomeration state caused a shift towards NP uptake via micropinocytosis. After NPs enter cells, studies have shown they can escape the lysosomal or endosomal compartment and spill into the cytosol. In this way, NPs have been shown to impact the mucus layer, mucus-producing cells, and intestinal epithelial cells [5]. These barriers serve to protect the host from pathogens, among other things, and their disruption can lead to autoantigen exposure and aberrant damage to cells [5]. Such impact of NPs on cells can produce danger signals, which further disrupts barrier function and threatens gut dysbiosis [5]. Therefore, NPs can negatively impact gut barrier function, potentially leading to the disruption of microbial homeostasis.