title: Critically ill patients demonstrate large interpersonal variation in intestinal microbiota dysregulation: a pilot study.
abstract: OBJECTIVE
  The intestinal microbiota has emerged as a virtual organ with essential functions in human physiology. Antibiotic-induced disruption of the microbiota in critically ill patients may have a negative influence on key energy resources and immunity. We set out to characterize the fecal microbiota composition in critically ill patients both with and without sepsis and to explore the use of microbiota-derived markers for clinical outcome measurements in this setting.
  
  
  METHODS
  In this prospective observational cohort study we analyzed the fecal microbiota of 34 patients admitted to the intensive care unit. Fifteen healthy subjects served as controls. The fecal microbiota was phylogenetically characterized by 16S rRNA gene sequencing, and associations with clinical outcome parameters were evaluated.
  
  
  RESULTS
  A marked shift in fecal bacterial composition was seen in all septic and non-septic critically ill patients compared with controls, with extreme interindividual differences. In 13 of the 34 patients, a single bacterial genus made up >50% of the gut microbiota; in 4 patients this was even >75%. A significant decrease in bacterial diversity was observed in half of the patients. No associations were found between microbiota diversity, Firmicutes/Bacteroidetes ratio, or Gram-positive/Gram-negative ratio and outcome measurements such as complications and survival.
  
  
  CONCLUSIONS
  We observed highly heterogeneous patterns of intestinal microbiota in both septic and non-septic critically ill patients. Nevertheless, some general patterns were observed, including disappearance of bacterial genera with important functions in host metabolism. More detailed knowledge of the short- and long-term health consequences of these major shifts in intestinal bacterial communities is needed.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ, Amsterdam, The Netherlands. j.m.lankelma@amc.uva.nl.
authors.forename: Jacqueline M
authors.identifier: http://orcid.org/0000-0001-9815-0231
authors.initials: JM
authors.lastname: Lankelma
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Lonneke A
authors.initials: LA
authors.lastname: van Vught
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Clara
authors.initials: C
authors.lastname: Belzer
authors.affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ, Amsterdam, The Netherlands.|Division of Infectious Diseases, Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.|Research Programs Unit Immunobiology, Department of Bacteriology and Immunology, Helsinki University, Helsinski, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room G2-130, 1105 AZ, Amsterdam, The Netherlands.|Division of Infectious Diseases, Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Wiersinga
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D015415:Biomarkers / Q000032:analysis*; D016638:Critical Illness; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010865:Pilot Projects; D011446:Prospective Studies; D018805:Sepsis / Q000382:microbiology*
chemical_list: D000900:Anti-Bacterial Agents; D015415:Biomarkers
keywords: Antibiotics; Critically ill; Gut microbiota; Intensive care unit; Sepsis