Effects of subchronic exposure of silver nanoparticles on intestinal microbiota and gut-associated immune responses in the ileum of Sprague-Dawley rats

Abstract

Silver nanoparticles (AgNP) are widely used for their antibacterial properties. Incorporation of AgNP into food-related products and health supplements represents a potential route for oral exposure to AgNP; however, the effects of such exposure on the gastrointestinal system are mostly unknown. This study evaluated changes in the populations of intestinal-microbiota and intestinal-mucosal gene expression in Sprague-Dawley rats (both male and female) that were gavaged orally with discrete sizes of AgNP (10, 75 and 110 nm) and silver acetate. Doses of AgNP (9, 18 and 36 mg/kg body weight/day) and silver acetate (100, 200 and 400 mg/kg body weight/day) were divided and administered to rats twice daily (∼10 h apart) for 13 weeks. The results indicate that AgNP prompted size- and dose-dependent changes to ileal-mucosal microbial populations, as well as, intestinal gene expression and induced an apparent shift in the gut microbiota toward greater proportions of Gram-negative bacteria. DNA-based analyses revealed that exposure to 10 nm AgNP and low-dose silver acetate caused a decrease in populations of Firmicutes phyla, along with a decrease in the Lactobacillus genus. Analysis of host gene expression demonstrated that smaller sizes and lower doses of AgNP exposure prompted the decreased expression of important immunomodulatory genes, including MUC3, TLR2, TLR4, GPR43 and FOXP3. Gender-specific effects to AgNP exposure were more prominent for the gut-associated immune responses. These results indicate that the oral exposure to AgNP alter mucosa-associated microbiota and modulate the gut-associated immune response and the overall homeostasis of the intestinal tract.

Is nano safe in foods? Establishing the factors impacting the gastrointestinal fate and toxicity of organic and inorganic food-grade nanoparticles

“…33 The strong antimicrobial activity of silver nanoparticles may also alter the nature of the gut microbiota, especially if they reach the colon. 12,34 The effects of the food matrix on the behavior of silver nanoparticles are ignored in cell culture studies, but one recent study showed that certain food components did have an appreciable impact on the absorption and toxicity of silver nanoparticles in intestinal cells. 35 A common issue with cell culture studies is that the dose of nanoparticles used is much higher than would ever be found in practice, and is therefore not physiologically relevant.…”

“…12,78 Any nanoparticles that are not digested or absorbed in the upper GIT will reach the lower GIT where they may alter the microbiome. 12,34 The ability of inorganic nanoparticles to produce toxicity is often associated with their chemical reactivity, which depends on their composition. For example, some inorganic nanoparticles dissolve and release ions that promote undesirable chemical or biochemical reactions (e.g., silver nanoparticles), whereas others are relatively inert (e.g., titanium dioxide nanoparticles).…”

The role of the food matrix and gastrointestinal tract in the assessment of biological properties of ingested engineered nanomaterials (iENMs): State of the science and knowledge gaps

“…Nanoparticles may also impact the intestinal microbiome. For example Williams et al reported size- and dose-dependent changes in ileal-mucosal bacterial populations, including a shift toward gram negative organisms, in rats gavaged with silver nanoparticles (Williams et al , 2015). The chemical reactivity and toxicity of inorganic ENMs is also closely related to their composition, e.g.…”

“…colitis), which could reveal potential human toxicity that would remain masked in healthy animals (Dixit and Boelsterli, 2007). Likewise, while growing evidence continues to emphasize the critical role of the gut microbiome and its role in overall health (Consortium, 2012; Pflughoeft and Versalovic, 2012; Theriot et al , 2014; Turnbaugh et al , 2009; Weir et al , 2013), potential effects of iENMs on the gut microbiome remain largely unstudied (Bergin and Witzmann, 2013; Wilding et al , 2016; Williams et al , 2015). …”

Small Size Silver Nanoparticle’s Corrosive and Hazardous Manifestations on Mature and Developing Kidney Following Accumulation in Pregnant Mice and Offspring’s after Serial Oral Bolus Experimental Application: A New Chapter in Teratogenicity and Toxicity Search

“…Verleysen et al in recent year proved TEM and SP-ICP-MS analysis says release of small size silver nanoparticles cause severe nephrotoxic effect in drug manufacturing process but also utilized significantly for decoration of pastry [26]. Williams et al reported effects of sub chronic exposure of silver nanoparticles on micro biota and lower animal cause severe nephrotoxicity [27]. Bastos et al propounded that the influence of Citrate or PEG coating on silver nanoparticle arouses toxicity to a human keratinocyte and kidney cell line [28].…”