title: Intestinal microbiome is related to lifetime antibiotic use in Finnish pre-school children.
abstract: Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2-7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.
authors.affiliation: Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014 Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Korpela
authors.affiliation: Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014 Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Salonen
authors.affiliation: Research Department, Social Insurance Institution, Turku, Peltolantie 3, 20720, Finland.
authors.forename: Lauri J
authors.initials: LJ
authors.lastname: Virta
authors.affiliation: Valio Limited, R&D, Meijeritie 4, 00370 Helsinki, Finland.
authors.forename: Riina A
authors.initials: RA
authors.lastname: Kekkonen
authors.affiliation: European Molecular Biology Laboratory, PO Box 1022.40, 69012 Heidelberg, Germany.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Forslund
authors.affiliation: European Molecular Biology Laboratory, PO Box 1022.40, 69012 Heidelberg, Germany.
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.affiliation: Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, Haartmaninkatu 3, PO Box 21, 00014 Helsinki, Finland.|Department of Veterinary Biosciences, University of Helsinki, PO Box 66, 00014 Helsinki, Finland.|Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D001424:Bacterial Infections / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool / Q000706:statistics & numerical data; D015331:Cohort Studies; D003631:Day Care, Medical / Q000706:statistics & numerical data; D005243:Feces / Q000382:microbiology; D005260:Female; D005387:Finland; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D018942:Macrolides / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides
references.citation: J Lipid Res. 2006 Feb;47(2):241-59
references.pmid: 16299351
references.citation: Clin Exp Allergy. 2005 Sep;35(9):1141-6
references.pmid: 16164439
references.citation: Pediatrics. 2006 Aug;118(2):511-21
references.pmid: 16882802
references.citation: Gut. 2007 May;56(5):661-7
references.pmid: 17047098
references.citation: Chest. 2007 Jun;131(6):1753-9
references.pmid: 17413050
references.citation: Diabetes. 2007 Jul;56(7):1761-72
references.pmid: 17456850
references.citation: Appl Environ Microbiol. 2007 Jul;73(14):4407-16
references.pmid: 17496134
references.citation: ISME J. 2007 May;1(1):56-66
references.pmid: 18043614
references.citation: Am J Clin Nutr. 2008 Mar;87(3):534-8
references.pmid: 18326589
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13580-5
references.pmid: 18757757
references.citation: BMC Pulm Med. 2008;8:19
references.pmid: 18822123
references.citation: BMJ. 2008;337:a2245
references.pmid: 19029175
references.citation: J Appl Microbiol. 2009 Feb;106(2):506-14
references.pmid: 19200317
references.citation: Pediatrics. 2009 Mar;123(3):1003-10
references.pmid: 19255032
references.citation: Clin Exp Allergy. 2009 Apr;39(4):518-26
references.pmid: 19220322
references.citation: FEMS Immunol Med Microbiol. 2009 Jun;56(1):80-7
references.pmid: 19385995
references.citation: Trends Pharmacol Sci. 2009 Nov;30(11):570-80
references.pmid: 19758712
references.citation: J Allergy Clin Immunol. 2009 Nov;124(5):982-9
references.pmid: 19895986
references.citation: Basic Clin Pharmacol Toxicol. 2010 Feb;106(2):86-94
references.pmid: 19961477
references.citation: Mucosal Immunol. 2010 Mar;3(2):148-58
references.pmid: 19940845
references.citation: Nat Methods. 2010 May;7(5):335-6
references.pmid: 20383131
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4554-61
references.pmid: 20847294
references.citation: Int J Obes (Lond). 2011 Apr;35(4):522-9
references.pmid: 21386800
references.citation: Arch Dis Child. 2011 Jun;96(6):590-5
references.pmid: 21233078
references.citation: Eur Respir J. 2011 Aug;38(2):295-302
references.pmid: 21233272
references.citation: Bioinformatics. 2011 Aug 15;27(16):2194-200
references.pmid: 21700674
references.citation: J Allergy Clin Immunol. 2011 Sep;128(3):646-52.e1-5
references.pmid: 21782228
references.citation: Clin Dev Immunol. 2012;2012:932072
references.pmid: 22110540
references.citation: Am J Epidemiol. 2012 Apr 15;175(8):775-84
references.pmid: 22366379
references.citation: EMBO Rep. 2012 May;13(5):440-7
references.pmid: 22422004
references.citation: Pediatrics. 2012 Jul;130(1):23-31
references.pmid: 22711728
references.citation: Nature. 2012 Aug 30;488(7413):621-6
references.pmid: 22914093
references.citation: Eur J Clin Nutr. 2012 Sep;66(9):1020-3
references.pmid: 22692023
references.citation: Antimicrob Agents Chemother. 2012 Nov;56(11):5811-20
references.pmid: 22948872
references.citation: Nucleic Acids Res. 2013 Jan 7;41(1):e1
references.pmid: 22933715
references.citation: Int J Obes (Lond). 2013 Jan;37(1):16-23
references.pmid: 22907693
references.citation: Genome Res. 2013 Jul;23(7):1163-9
references.pmid: 23568836
references.citation: Nature. 2013 Aug 29;500(7464):541-6
references.pmid: 23985870
references.citation: PLoS One. 2014;9(6):e90702
references.pmid: 24603757
references.citation: PLoS Comput Biol. 2014 Apr;10(4):e1003531
references.pmid: 24699258
references.citation: BMJ. 2014;348:g2267
references.pmid: 24735883
references.citation: Proc Natl Acad Sci U S A. 2014 May 20;111(20):7421-6
references.pmid: 24799697
references.citation: Nature. 2014 Jun 19;510(7505):417-21
references.pmid: 24896187
references.citation: Cell. 2014 Aug 14;158(4):705-21
references.pmid: 25126780
references.citation: JAMA Pediatr. 2014 Nov;168(11):1063-9
references.pmid: 25265089
references.citation: Cell. 2014 Nov 6;159(4):789-99
references.pmid: 25417156
references.citation: Dis Model Mech. 2015 Jan;8(1):1-16
references.pmid: 25561744
references.citation: J Clin Microbiol. 2015 Feb;53(2):626-35
references.pmid: 25520446
references.citation: MBio. 2015;6(1). pii: e02419-14. doi: 10.1128/mBio.02419-14
references.pmid: 25650398
references.citation: Pediatrics. 2015 Apr;135(4):617-26
references.pmid: 25825533
references.citation: Nat Commun. 2015;6:7486
references.pmid: 26123276
references.citation: Infect Immun. 2004 Sep;72(9):4996-5003
references.pmid: 15321991
references.citation: Br J Nutr. 1998 Feb;79(2):185-94
references.pmid: 9536863
references.citation: Am J Clin Nutr. 1958 Jul-Aug;6(4):430-8
references.pmid: 13559171
references.citation: Poult Sci. 2005 Apr;84(4):634-43
references.pmid: 15844822
references.citation: Int Arch Allergy Immunol. 2006;140(2):157-63
references.pmid: 16601353