**1. Introduction**

It is estimated that there are 600 million cases of foodborne illnesses and 420,000 deaths annually worldwide. Unsafe foods are a risk to human health and countries' economy and mainly affect people at risk of exclusion, migrants and population under conflicts. The majority of foodborne diseases are related to pathogenic bacteria belonging to the genera *Salmonella*, *Listeria*, *Escherichia*, *Clostridium* and *Campylobacter*. Microbial contamination of food can occur at different stages of the process, such as harvesting, slaughtering, processing and distribution ("farm to fork") and can be caused by environmental contamination, such as water, soil or air [1]. The most common symptoms of foodborne diseases are gastrointestinal, such as diarrhea, but other consequences may be kidney and liver failure, brain and neural disorders, reactive arthritis and others. These diseases can be more severe in children, pregnant women, the elderly and those with a weakened immune system [2]. Traditional techniques such as salting, drying, freezing or fermentation are applied to extend the shelf life of food products, but there may be risk of recontamination. Therefore, there is a continuous need for antimicrobial agents that act in both food processing (preservation) and packaging (safety) stages [3].

In recent years, nanotechnology has experienced a noticeable rise in its applications, from agri-food to biotechnology, going through the engineering, cosmetic and textile industry. It can be considered a technological revolution [4]. Focusing on the field of food and health, nanotechnology is used in drug delivery system and nutrient release systems (nanoencapsulation), increasing the rate of recognition of disease symptoms and providing rapid treatments. It can also be applied to crops in the form of fertilizers and nanoscale additives or create nanoscale sensors to detect chemical, viral or bacterial contamination. In the case of food processing, it is a still emerging but promising technology [5].

Nanomaterials can be natural, accidental or manufactured and can be constituted by loose particles, aggregates or agglomerate in the form of nanoparticles, nanotubes, nanowires, nanofibers, and others. Of these, nanoparticles (NPs), wherein 50% or more of them in the numerical granulometry have one or more of the external dimensions between 1 and 100 nanometers, are possibly the most studied and the ones having more variety of sizes and shapes, which results in a large number of technological applications [6–8].

NPs are generally classified into organic and inorganic. Organic NPs incorporate carbon, whereas inorganic NPs incorporate metallic (Ag, Au, Cu), magnetic (Co, Fe, Ni), and/or semi-conductor components (ZnO, ZnS, CdS) [9]. Focusing our interest on silver nanoparticles (Ag-NPs), these have been widely used in medicine and biotechnology fields, due to their properties as antimicrobials. In this sense, numerous research studies have confirmed the effectiveness of Ag-NPs to inhibit the growth of pathogenic bacteria such as *Staphylococcus aureus*, *Streptococcus mutans*, *Streptococcus pyogenes*, *Escherichia coli* and *Proteus vulgaris* [10–12]. Interestingly, this activity has been also demonstrated using Ag-NPs obtained by 'biological methods' which are considered a great tool to reduce the negative effects associated with traditional nanoparticle synthesis commonly used in the laboratory [13]. In particular, two recent studies have shown the antimicrobial activity of Ag-NPs from apple pomace and from exopolysaccharides isolated from green microalgae against *E. coli* and *S. aureus* [14,15].

Shape, size, surface and charge are highlighted as the factors that influence the antimicrobial properties of Ag-NPs (Figure 1). Regarding shape (i.e., triangular, decahedron, spherical, cubic, platelet, among others), the spherical and the triangular forms seem to lead to higher antimicrobial activity [16–18]. Size is one of the most important factors when synthesizing nanoparticles, 1 to 30 nm being the most widely used range. Many studies have shown the size-dependent antibacterial activity of Ag-NPs [19–22]. Concerning the nanoparticle surface, it may be modified through the addition of coating agents, such as polymers (chitosan, polyethyleneimine, polyethylene glycol, polygamma glutamic acid), proteins (milk casein, bovine serum albumin, human serum albumin), antioxidants (glutathione) and/or polyvalent anion salts. Finally, the charge of the Ag-NPs determines their interaction with biological environments and its cellular uptake, which leads to a modulation of its antibacterial activity. Moreover, the antimicrobial activity of silver nanoparticles is bacteria strain- and cell wall structure-dependent [23].

The mechanisms of action by which Ag-NPs exert their antimicrobial effects are not completely clear, but two main hypothesis have been proposed: (*i*) a direct interaction of the nanoparticle with the cell membrane, and (*ii*) the release of ionic silver [24]. In the first hypothesis, the Ag-NPs would be adhered to the cell membrane via electrostatic attractions between the positive charges of the nanoparticles and the negative charges of the cells [25] or via the interaction of the nanoparticles into the sulfur and phosphorylated proteins present in the cell wall [26]. In any case, the interaction of the Ag-NPs with the cell membrane would produce its partial dissolution (Figure 1). In the second hypothesis, the Ag-NPs would enter into the cell and lead to a release of silver ions and the subsequent increase of reactive oxygen species (ROS) that would damage the enzymes involved in the cellular oxidation-reduction respiratory process and be finally responsible for cell death [16] (Figure 1). The two hypotheses could occur together as it has been showed that after interaction of the nanoparticle with the cell membrane, an internalization step takes place. In turn, this process can be affected by the nanoparticle charge [27]. Despite the antimicrobial effectiveness, some bacterial resistance against silver nanoparticles has been reported. Mechanisms such as negative regulation of porins, chromosomal resistance genes or plasmids with resistance genes have been proposed. However, this is still a field under study and more information to clarify this point at the frame of the food industry is clearly needed [24,28].

**Figure 1.** Main factors of influence and hypothetical mechanisms for the antimicrobial activity of silver nanoparticles.

On the other hand, the increased incorporation of silver nanoparticles into consumer products makes it essential to address their potential risk for human health. Nevertheless, there is still a lack of knowledge about their specific aspects of the intestinal uptake of silver nanoparticles [5]. The oral route of exposure has been poorly explored, despite the incorporation of such nanoparticles into packaging in contact with foods. After their ingestion, these nanoparticles pass through the digestive tract, where they may undergo physicochemical transformations, with consequences for the luminal environment, before crossing the epithelial barrier to reach the systemic compartment. Therefore, Ag-NPs toxicity and in particular, their effects at the gut level, are major concerns in the use and development of these nanomaterials.

This review presents a detailed description on the main applications of silver nanoparticles as antimicrobial agents for food control, as well as the current legislation concerning these materials. In addition, we summarize current knowledge about the impact of the dietary exposure to silver nanoparticles in human health with special emphasis in the gastrointestinal environment and microbiota, and highlight the areas where information is lacking. Finally, conclusions and future directions about both topics are summarized.
