title: Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.
abstract: Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Candon
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Perez-Arroyo
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Cindy
authors.initials: C
authors.lastname: Marquet
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Valette
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Anne-Perrine
authors.initials: AP
authors.lastname: Foray
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pelletier
authors.forename: Christian
authors.initials: C
authors.lastname: Milani
authors.affiliation: Laboratory of Probiogenomics, Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Milani
authors.affiliation: Laboratory of Probiogenomics, Department of Life Sciences, University of Parma, Parma, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ventura
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bach
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, F-75475, Paris, France; INSERM U1151, Hôpital Necker-Enfants Malades, Paris, France; CNRS UMR 8253, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: Lucienne
authors.initials: L
authors.lastname: Chatenoud
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D015994:Incidence; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D016688:Mice, Inbred NOD; D009092:Mucous Membrane / Q000276:immunology; D013154:Spleen / Q000276:immunology; D014640:Vancomycin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin