title: Same Exposure but Two Radically Different Responses to Antibiotics: Resilience of the Salivary Microbiome versus Long-Term Microbial Shifts in Feces.
abstract: Due to the spread of resistance, antibiotic exposure receives increasing attention. Ecological consequences for the different niches of individual microbiomes are, however, largely ignored. Here, we report the effects of widely used antibiotics (clindamycin, ciprofloxacin, amoxicillin, and minocycline) with different modes of action on the ecology of both the gut and the oral microbiomes in 66 healthy adults from the United Kingdom and Sweden in a two-center randomized placebo-controlled clinical trial. Feces and saliva were collected at baseline, immediately after exposure, and 1, 2, 4, and 12 months after administration of antibiotics or placebo. Sequences of 16S rRNA gene amplicons from all samples and metagenomic shotgun sequences from selected baseline and post-antibiotic-treatment sample pairs were analyzed. Additionally, metagenomic predictions based on 16S rRNA gene amplicon data were performed using PICRUSt. The salivary microbiome was found to be significantly more robust, whereas the antibiotics negatively affected the fecal microbiome: in particular, health-associated butyrate-producing species became strongly underrepresented. Additionally, exposure to different antibiotics enriched genes associated with antibiotic resistance. In conclusion, healthy individuals, exposed to a single antibiotic treatment, undergo considerable microbial shifts and enrichment in antibiotic resistance in their feces, while their salivary microbiome composition remains unexpectedly stable. The health-related consequences for the gut microbiome should increase the awareness of the individual risks involved with antibiotic use, especially in a (diseased) population with an already dysregulated microbiome. On the other hand, understanding the mechanisms behind the resilience of the oral microbiome toward ecological collapse might prove useful in combating microbial dysbiosis elsewhere in the body.
  
  
  OBJECTIVE
  Many health care professionals use antibiotic prophylaxis strategies to prevent infection after surgery. This practice is under debate since it enhances the spread of antibiotic resistance. Another important reason to avoid nonessential use of antibiotics, the impact on our microbiome, has hardly received attention. In this study, we assessed the impact of antibiotics on the human microbial ecology at two niches. We followed the oral and gut microbiomes in 66 individuals from before, immediately after, and up to 12 months after exposure to different antibiotic classes. The salivary microbiome recovered quickly and was surprisingly robust toward antibiotic-induced disturbance. The fecal microbiome was severely affected by most antibiotics: for months, health-associated butyrate-producing species became strongly underrepresented. Additionally, there was an enrichment of genes associated with antibiotic resistance. Clearly, even a single antibiotic treatment in healthy individuals contributes to the risk of resistance development and leads to long-lasting detrimental shifts in the gut microbiome.
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands e.zaura@acta.nl.
authors.forename: Egija
authors.initials: E
authors.lastname: Zaura
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Brandt
authors.affiliation: Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: M Joost
authors.initials: MJ
authors.lastname: Teixeira de Mattos
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Buijs
authors.affiliation: Research Group Microbiology and Systems Biology, TNO Earth, Life and Social Sciences, Zeist, The Netherlands.
authors.forename: Martien P M
authors.initials: MP
authors.lastname: Caspers
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Mamun-Ur
authors.initials: MU
authors.lastname: Rashid
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Andrej
authors.initials: A
authors.lastname: Weintraub
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Nord
authors.affiliation: Helperby Therapeutics Limited, London, United Kingdom.
authors.forename: Ann
authors.initials: A
authors.lastname: Savell
authors.affiliation: Helperby Therapeutics Limited, London, United Kingdom.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Helperby Therapeutics Limited, London, United Kingdom.
authors.forename: Antony R
authors.initials: AR
authors.lastname: Coates
authors.affiliation: Genetics and Genomic Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Hubank
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Spratt
authors.affiliation: Department of Microbial Diseases, UCL Eastman Dental Institute, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Research Group Microbiology and Systems Biology, TNO Earth, Life and Social Sciences, Zeist, The Netherlands.
authors.forename: Bart J F
authors.initials: BJ
authors.lastname: Keijser
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Crielaard
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D005243:Feces / Q000382:microbiology*; D064368:Healthy Volunteers; D006801:Humans; D064307:Microbiota / Q000187:drug effects*; D010919:Placebos / Q000008:administration & dosage; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012463:Saliva / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D013548:Sweden; D013997:Time Factors; D006113:United Kingdom
chemical_list: D000900:Anti-Bacterial Agents; D004275:DNA, Ribosomal; D010919:Placebos; D012336:RNA, Ribosomal, 16S