title: Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota.
abstract: OBJECTIVE
  The gut microbiota is a complex and densely populated community in a dynamic environment determined by host physiology. We investigated how intestinal oxygen levels affect the composition of the fecal and mucosally adherent microbiota.
  
  
  METHODS
  We used the phosphorescence quenching method and a specially designed intraluminal oxygen probe to dynamically quantify gut luminal oxygen levels in mice. 16S ribosomal RNA gene sequencing was used to characterize the microbiota in intestines of mice exposed to hyperbaric oxygen, human rectal biopsy and mucosal swab samples, and paired human stool samples.
  
  
  RESULTS
  Average Po2 values in the lumen of the cecum were extremely low (<1 mm Hg). In altering oxygenation of mouse intestines, we observed that oxygen diffused from intestinal tissue and established a radial gradient that extended from the tissue interface into the lumen. Increasing tissue oxygenation with hyperbaric oxygen altered the composition of the gut microbiota in mice. In human beings, 16S ribosomal RNA gene analyses showed an increased proportion of oxygen-tolerant organisms of the Proteobacteria and Actinobacteria phyla associated with rectal mucosa, compared with feces. A consortium of asaccharolytic bacteria of the Firmicute and Bacteroidetes phyla, which primarily metabolize peptones and amino acids, was associated primarily with mucus. This could be owing to the presence of proteinaceous substrates provided by mucus and the shedding of the intestinal epithelium.
  
  
  CONCLUSIONS
  In an analysis of intestinal microbiota of mice and human beings, we observed a radial gradient of microbes linked to the distribution of oxygen and nutrients provided by host tissue.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Albenberg
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Esipova
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Colleen P
authors.initials: CP
authors.lastname: Judge
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Kyle
authors.initials: K
authors.lastname: Bittinger
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Alice
authors.initials: A
authors.lastname: Laughlin
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Grunberg
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Baldassano
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, University of Maryland, Baltimore, Maryland.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Frederic D
authors.initials: FD
authors.lastname: Bushman
authors.affiliation: Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: vinograd@mail.med.upenn.edu.
authors.forename: Sergei A
authors.initials: SA
authors.lastname: Vinogradov
authors.affiliation: Division of Gastroenterology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: gdwu@mail.med.upenn.edu.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Wu
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004058:Diffusion; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D006931:Hyperbaric Oxygenation; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D064307:Microbiota; D010092:Oximetry; D010100:Oxygen / Q000378:metabolism*; D012329:RNA, Bacterial / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D021521:Ribotyping
chemical_list: D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D010100:Oxygen
keywords: Aerobic; Anaerobic; Microbe; Spatial Gradient of Oxygen