title: Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high-fat diet.
abstract: BACKGROUND
  Obesity, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD) are serious health concerns, especially in Western populations. Antibiotic exposure and high-fat diet (HFD) are important and modifiable factors that may contribute to these diseases.
  
  
  METHODS
  To investigate the relationship of antibiotic exposure with microbiome perturbations in a murine model of growth promotion, C57BL/6 mice received lifelong sub-therapeutic antibiotic treatment (STAT), or not (control), and were fed HFD starting at 13 weeks. To characterize microbiota changes caused by STAT, the V4 region of the 16S rRNA gene was examined from collected fecal samples and analyzed.
  
  
  RESULTS
  In this model, which included HFD, STAT mice developed increased weight and fat mass compared to controls. Although results in males and females were not identical, insulin resistance and NAFLD were more severe in the STAT mice. Fecal microbiota from STAT mice were distinct from controls. Compared with controls, STAT exposure led to early conserved diet-independent microbiota changes indicative of an immature microbial community. Key taxa were identified as STAT-specific and several were found to be predictive of disease. Inferred network models showed topological shifts concurrent with growth promotion and suggest the presence of keystone species.
  
  
  CONCLUSIONS
  These studies form the basis for new models of type 2 diabetes and NAFLD that involve microbiome perturbation.
authors.forename: Douglas
authors.initials: D
authors.lastname: Mahana
authors.forename: Chad M
authors.initials: CM
authors.lastname: Trent
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Kurtz
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Bokulich
authors.forename: Thomas
authors.initials: T
authors.lastname: Battaglia
authors.forename: Jennifer
authors.initials: J
authors.lastname: Chung
authors.forename: Christian L
authors.initials: CL
authors.lastname: Müller
authors.forename: Huilin
authors.initials: H
authors.lastname: Li
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bonneau
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Blaser
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D044822:Biodiversity; D001823:Body Composition; D001835:Body Weight; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006728:Hormones / Q000097:blood; D018836:Inflammation Mediators / Q000097:blood; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism* / Q000382:microbiology; D054892:Metagenome; D056186:Metagenomics; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000378:metabolism / Q000382:microbiology; D010641:Phenotype; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D006728:Hormones; D018836:Inflammation Mediators; D007328:Insulin; D012336:RNA, Ribosomal, 16S; D005947:Glucose