title: Signatures of early frailty in the gut microbiota.
abstract: BACKGROUND
  Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care-dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing.
  
  
  METHODS
  We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence.
  
  
  RESULTS
  Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty-two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity.
  
  
  CONCLUSIONS
  There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Jackson
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK. matthew.jackson@kcl.ac.uk.
authors.forename: Matt
authors.initials: M
authors.lastname: Jackson
authors.affiliation: School of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. ianjeffery2@gmail.com.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Jeffery
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK. madison.taylor-smith@kcl.ac.uk.
authors.forename: Michelle
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK. jordana.bell@kcl.ac.uk.
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. ac347@cornell.edu.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. rel222@cornell.edu.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: School of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. pwotoole@ucc.ie.
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Toole
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK. tim.spector@kcl.ac.uk.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, St Thomas' Hospital Campus, 3rd & 4th Floor South Wing Block D, Westminster Bridge Road, London, SE1 7EH, UK. claire.j.steves@kcl.ac.uk.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Steves
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology*; D005260:Female; D016330:Frail Elderly; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008875:Middle Aged; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D012307:Risk Factors; D017423:Sequence Analysis, RNA; D014427:Twins
chemical_list: D012336:RNA, Ribosomal, 16S
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