title: Normoxic Recovery Mimicking Treatment of Sleep Apnea Does Not Reverse Intermittent Hypoxia-Induced Bacterial Dysbiosis and Low-Grade Endotoxemia in Mice.
abstract: Intermittent hypoxia (IH) mimicking obstructive sleep apnea (OSA) significantly modifies gut microbiota in mice. However, whether these IH-induced gut microbiome changes are reversible after restoring normal oxygenation (the equivalent of effective OSA therapy) is unknown. The aim of this study was to investigate gut microbiota composition and circulating endotoxemia after a post-IH normoxic period in a mouse model of OSA.
  
  
  
  Ten mice were subjected to IH (40 sec 21% O2-20 sec 5% O2) for 6 h/day for 6 w and 10 mice breathing normoxic air (NM) were used as controls. After exposures, both groups were subjected to 6 w in normoxia. Microbiome composition of fecal samples was determined by 16S ribosomal RNA (rRNA) pyrosequencing. Bioinformatic analysis was performed by Quantitative Insights into Microbial Ecology. Plasma lipopolysaccharide (LPS) levels were measured by endotoxin assay.
  
  
  
  After normoxic recovery, the Chao and Shannon indices of each group suggested similar bacterial richness and diversity. 16S rRNA pyrosequencing analysis showed that IH-exposed mice had a significant decrease in the abundance ofBacteroidetesand a significant increase ofFirmicutesandDeferribacterescompared to the NM group. After normoxic recovery, circulating LPS concentrations were higher in the IH group (P < 0.009). Moreover, the IH group showed a negative and significant correlation between the abundance ofLactobacillusandRuminococcusand significant positive correlations between the abundance ofMucispirillumandDesulfovibrioand plasma LPS levels, respectively.
  
  
  
  Even after prolonged normoxic recovery after IH exposures, gut microbiota and circulating endotoxemia remain negatively altered, suggesting that potential benefits of OSA treatment for reversing OSA-induced changes in gut microbiota may either require a longer period or alternative interventions.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBER, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Moreno-Indias
authors.affiliation: Laboratori del Son, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBER, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torres
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBER, Madrid, Spain.
authors.forename: Lidia
authors.initials: L
authors.lastname: Sanchez-Alcoholado
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBER, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Cardona
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBER, Madrid, Spain.|Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Department of Pediatrics, Biological Sciences Division, Pritzker School of Medicine, The University of Chicago, Chicago, IL.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
authors.affiliation: Laboratori del Son, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBER, Madrid, Spain.|Institut Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Montserrat
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBER, Madrid, Spain.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Queipo-Ortuño
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBER, Madrid, Spain.|Institut Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.|Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona-IDIBAPS, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology*; D019446:Endotoxemia / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D000860:Hypoxia / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020127:Recovery of Function; D020181:Sleep Apnea, Obstructive / Q000139:chemically induced / Q000382:microbiology / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D008070:Lipopolysaccharides
keywords: endotoxemia; gut microbiota; intermittent hypoxia; obstructive sleep apnea; sleep apnea therapy