title: Alterations in fecal microbiota composition by probiotic supplementation in healthy adults: a systematic review of randomized controlled trials.
abstract: The effects of probiotic supplementation on fecal microbiota composition in healthy adults have not been well established. We aimed to provide a systematic review of the potential evidence for an effect of probiotic supplementation on the composition of human fecal microbiota as assessed by high-throughput molecular approaches in randomized controlled trials (RCTs) of healthy adults.
  
  
  
  The survey of peer-reviewed papers was performed on 17 August 2015 by a literature search through PubMed, SCOPUS, and ISI Web of Science. Additional papers were identified by checking references of relevant papers. Search terms included healthy adult, probiotic, bifidobacterium, lactobacillus, gut microbiota, fecal microbiota, intestinal microbiota, intervention, and (clinical) trial. RCTs of solely probiotic supplementation and placebo in healthy adults that examined alteration in composition of overall fecal microbiota structure assessed by shotgun metagenomic sequencing, 16S ribosomal RNA sequencing, or phylogenetic microarray methods were included. Independent collection and quality assessment of studies were performed by two authors using predefined criteria including methodological quality assessment of reports of the clinical trials based on revised tools from PRISMA/Cochrane and by the Jadad score.
  
  
  
  Seven RCTs investigating the effect of probiotic supplementation on fecal microbiota in healthy adults were identified and included in the present systematic review. The quality of the studies was assessed as medium to high. Still, no effects were observed on the fecal microbiota composition in terms of α-diversity, richness, or evenness in any of the included studies when compared to placebo. Only one study found that probiotic supplementation significantly modified the overall structure of the fecal bacterial community in terms of β-diversity when compared to placebo.
  
  
  
  This systematic review of the pertinent literature demonstrates a lack of evidence for an impact of probiotics on fecal microbiota composition in healthy adults. Future studies would benefit from pre-specifying the primary outcome and transparently reporting the results including effect sizes, confidence intervals, and P values as well as providing a clear distinction of between-group and within-group comparisons.
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark. nadja@sund.ku.dk.
authors.forename: Nadja B
authors.initials: NB
authors.lastname: Kristensen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bryrup
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark.
authors.forename: Kristine H
authors.initials: KH
authors.lastname: Allin
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark.
authors.forename: Trine
authors.initials: T
authors.lastname: Nielsen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark.
authors.forename: Tue H
authors.initials: TH
authors.lastname: Hansen
authors.affiliation: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 1, 2nd floor, Copenhagen Ø, 2100, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D001419:Bacteria / Q000145:classification* / Q000235:genetics; D005243:Feces / Q000382:microbiology*; D064368:Healthy Volunteers; D006801:Humans; D064307:Microbiota; D010802:Phylogeny; D019936:Probiotics / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic / Q000592:standards