title: Gut microbiota disturbance during antibiotic therapy: a multi-omic approach.
abstract: OBJECTIVE
  Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy.
  
  
  METHODS
  The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS(2) instrument [UPLC-LTQ Orbitrap-MS/MS]) of a patient undergoing AB therapy for 14 days were evaluated.
  
  
  RESULTS
  Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by 'presumptive' naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while 'presumptively' attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host-microbial interactions significantly improved after treatment cessation.
  
  
  CONCLUSIONS
  This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.
authors.affiliation: Unidad Mixta de Investigación en Genómica y Salud del Centro Superior de Investigación en Salud Pública (CSISP) e Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universitat de València, , Valencia, Spain.
authors.forename: Ana Elena
authors.initials: AE
authors.lastname: Pérez-Cobas
authors.forename: María José
authors.initials: MJ
authors.lastname: Gosalbes
authors.forename: Anette
authors.initials: A
authors.lastname: Friedrichs
authors.forename: Henrik
authors.initials: H
authors.lastname: Knecht
authors.forename: Alejandro
authors.initials: A
authors.lastname: Artacho
authors.forename: Kathleen
authors.initials: K
authors.lastname: Eismann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: David
authors.initials: D
authors.lastname: Rojo
authors.forename: Rafael
authors.initials: R
authors.lastname: Bargiela
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Sven C
authors.initials: SC
authors.lastname: Neulinger
authors.forename: Carolin
authors.initials: C
authors.lastname: Däumer
authors.forename: Femke-Anouska
authors.initials: FA
authors.lastname: Heinsen
authors.forename: Amparo
authors.initials: A
authors.lastname: Latorre
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.forename: Jana
authors.initials: J
authors.lastname: Seifert
authors.forename: Vitor Martins
authors.initials: VM
authors.lastname: dos Santos
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Ott
authors.forename: Manuel
authors.initials: M
authors.lastname: Ferrer
authors.forename: Andrés
authors.initials: A
authors.lastname: Moya
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000145:classification / Q000187:drug effects* / Q000302:isolation & purification; D015373:Bacterial Typing Techniques / Q000379:methods; D044822:Biodiversity; D004269:DNA, Bacterial / Q000032:analysis; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000378:metabolism / Q000382:microbiology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D055442:Metabolome / Q000187:drug effects; D064307:Microbiota / Q000187:drug effects*; D012329:RNA, Bacterial / Q000032:analysis; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D047090:beta-Lactams