title: Dietary silver nanoparticles can disturb the gut microbiota in mice.
abstract: Humans are increasingly exposed via the diet to Ag nanoparticles (NP) used in the food industry. Because of their anti-bacterial activity, ingested Ag NP might disturb the gut microbiota that is essential for local and systemic homeostasis. We explored here the possible impact of dietary Ag NP on the gut microbiota in mice at doses relevant for currently estimated human intake.
  
  
  
  Mice were orally exposed to food (pellets) supplemented with increasing doses of Ag NP (0, 46, 460 or 4600 ppb) during 28 d. Body weight, systemic inflammation and gut integrity were investigated to determine overall toxicity, and feces DNA collected from the gut were analyzed by Next Generation Sequencing (NGS) to assess the effect of Ag NP on the bacterial population. Ag NP were characterized alone and in the supplemented pellets by scanning transmission electron microscopy (STEM) and energy dispersive X-ray analysis (EDX).
  
  
  
  No overall toxicity was recorded in mice exposed to Ag NP. Ag NP disturbed bacterial evenness (α-diversity) and populations (β-diversity) in a dose-dependent manner. Ag NP increased the ratio between Firmicutes (F) and Bacteroidetes (B) phyla. At the family level, Lachnospiraceae and the S24-7 family mainly accounted for the increase in Firmicutes and decrease in Bacteroidetes, respectively. Similar effects were not observed in mice identically exposed to the same batch of Ag NP-supplemented pellets aged during 4 or 8 months and the F/B ratio was less or not modified. Analysis of Ag NP-supplemented pellets showed that freshly prepared pellets released Ag ions faster than aged pellets. STEM-EDX analysis also showed that Ag sulfidation occurred in aged Ag NP-supplemented pellets.
  
  
  
  Our data indicate that oral exposure to human relevant doses of Ag NP can induce microbial alterations in the gut. The bacterial disturbances recorded after Ag NP are similar to those reported in metabolic and inflammatory diseases, such as obesity. It also highlights that Ag NP aging in food, and more specifically sulfidation, can reduce the effects of Ag NP on the microbiota by limiting the release of toxic Ag ions.
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue E. Mounier 52 - bte B1.52.12, 1200, Brussels, Belgium. sybille.vandenbrule@uclouvain.be.
authors.forename: Sybille
authors.initials: S
authors.lastname: van den Brule
authors.affiliation: Centre de Technologies Moléculaires Appliquées, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Clos Chapelle-aux-champs 30 bte B1.30.24, 1200, Brussels, Belgium.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Ambroise
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue E. Mounier 52 - bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Lecloux
authors.affiliation: CEREGE, Aix Marseille Université, CNRS, IRD, UM34, UMR 7330, Europole de l'arbois - BP 80, 13545, Aix en Provence, France.
authors.forename: Clément
authors.initials: C
authors.lastname: Levard
authors.affiliation: CEA LITEN Grenoble, 17 Rue des Martyrs, 38054, GRENOBLE - CEDEX 9, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Soulas
authors.affiliation: Electron Microscopy Unit, Veterinary and Agrochemical Research Centre (CODA-CERVA), Groeselenberg 99, 1180, Brussels, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: De Temmerman
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue E. Mounier 52 - bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Mihaly
authors.initials: M
authors.lastname: Palmai-Pallag
authors.affiliation: De Duve Institute, Université catholique de Louvain, Avenue Hippocrate 75 - bte B1.75.02, 1200, Brussels, Belgium.
authors.forename: Etienne
authors.initials: E
authors.lastname: Marbaix
authors.affiliation: Louvain centre for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Avenue E. Mounier 52 - bte B1.52.12, 1200, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D007422:Intestines / Q000382:microbiology*; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D064307:Microbiota; D017348:Microscopy, Electron, Scanning Transmission; D012834:Silver / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission
chemical_list: D012834:Silver
keywords: Bacteria; Dysbiosis; Food; NGS; Nanomaterials; Sulfidation; Toxicity