title: Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.
abstract: The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Tregproportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Alexandra E
authors: AE
authors: Livanos
authors: Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden.
authors: Thomas U
authors: TU
authors: Greiner
authors: Biomedical Informatics and Computational Biology Program, University of Minnesota, Minneapolis, Minneapolis 55455, USA.
authors: Pajau
authors: P
authors: Vangay
authors: Systems and Translational Sciences, RTI International, Research Triangle Park, North Carolina 27709, USA.
authors: Wimal
authors: W
authors: Pathmasiri
authors: Systems and Translational Sciences, RTI International, Research Triangle Park, North Carolina 27709, USA.
authors: Delisha
authors: D
authors: Stewart
authors: Systems and Translational Sciences, RTI International, Research Triangle Park, North Carolina 27709, USA.
authors: Susan
authors: S
authors: McRitchie
authors: Departments of Population Health, New York University Langone Medical Center, New York, New York 10016, USA.
authors: Huilin
authors: H
authors: Li
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Jennifer
authors: J
authors: Chung
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Jiho
authors: J
authors: Sohn
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Sara
authors: S
authors: Kim
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Zhan
authors: Z
authors: Gao
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Cecily
authors: C
authors: Barber
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Joanne
authors: J
authors: Kim
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Sandy
authors: S
authors: Ng
authors: Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA.
authors: Arlin B
authors: AB
authors: Rogers
authors: Systems and Translational Sciences, RTI International, Research Triangle Park, North Carolina 27709, USA.
authors: Susan
authors: S
authors: Sumner
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
authors: Xue-Song
authors: XS
authors: Zhang
authors: Department of Microbiology, New York University Langone Medical Center, New York, New York 10016, USA.|Skirball Institute, New York University Langone Medical Center, New York, New York 10016, USA.
authors: Ken
authors: http://orcid.org/0000-0002-5860-0661
authors: K
authors: Cadwell
authors: Computer Science and Engineering, University of Minnesota, Minneapolis, Minneapolis 55455, USA.|Biotechnology Institute, University of Minnesota, Saint Paul, Minneapolis 55108, USA.
authors: Dan
authors: D
authors: Knights
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.|CHIBI, New York University Langone Medical Center, New York, New York 10016, USA.
authors: Alexander
authors: A
authors: Alekseyenko
authors: Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden.|Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
authors: Fredrik
authors: F
authors: Bäckhed
authors: Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.|New York Harbor Veterans Affairs Medical Center, New York, New York 10010, USA.
authors: Martin J
authors: MJ
authors: Blaser
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002784:Cholesterol / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D004334:Drug Administration Schedule; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D050356:Lipid Metabolism / Q000187:drug effects; D055442:Metabolome / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology; D009765:Obesity; D010404:Penicillin V / Q000008:administration & dosage / Q000009:adverse effects*; D012336:RNA, Ribosomal, 16S; D050378:T-Lymphocytes, Regulatory; D058504:Th17 Cells
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S; D002784:Cholesterol; D010404:Penicillin V