title: Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice.
abstract: Chronic sleep fragmentation (SF) commonly occurs in human populations, and although it does not involve circadian shifts or sleep deprivation, it markedly alters feeding behaviors ultimately promoting obesity and insulin resistance. These symptoms are known to be related to the host gut microbiota. Mice were exposed to SF for 4 weeks and then allowed to recover for 2 weeks. Taxonomic profiles of fecal microbiota were obtained prospectively, and conventionalization experiments were performed in germ-free mice. Adipose tissue insulin sensitivity and inflammation, as well as circulating measures of inflammation, were assayed. Effect of fecal water on colonic epithelial permeability was also examined. Chronic SF-induced increased food intake and reversible gut microbiota changes characterized by the preferential growth of highly fermentative members of Lachnospiraceae and Ruminococcaceae and a decrease of Lactobacillaceae families. These lead to systemic and visceral white adipose tissue inflammation in addition to altered insulin sensitivity in mice, most likely via enhanced colonic epithelium barrier disruption. Conventionalization of germ-free mice with SF-derived microbiota confirmed these findings. Thus, SF-induced metabolic alterations may be mediated, in part, by concurrent changes in gut microbiota, thereby opening the way for gut microbiome-targeted therapeutics aimed at reducing the major end-organ morbidities of chronic SF.
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.|Department of Medical Oncology, City of Hope, Duarte, CA, 91010, USA.
authors.forename: Valeriy A
authors.initials: VA
authors.lastname: Poroyko
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alba
authors.initials: A
authors.lastname: Carreras
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Abdelnaby
authors.initials: A
authors.lastname: Khalyfa
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Ahamed A
authors.initials: AA
authors.lastname: Khalyfa
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eduard
authors.initials: E
authors.lastname: Peris
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Gileles-Hillel
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Zhuanhong
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Hubert
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, CIBER, Madrid, Spain.|Institut Investigacions Biomediques August Pi 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
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.affiliation: Section of Pediatric Sleep Medicine, Department of Pediatrics, Pritzker School of Medicine, Biological Sciences Division, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gozal
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D000069196:Gastrointestinal Microbiome; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007378:Interleukins / Q000097:blood; D007777:Lactobacillaceae / Q000302:isolation & purification; D020738:Leptin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012892:Sleep Deprivation / Q000097:blood / Q000378:metabolism / Q000382:microbiology*
chemical_list: D007328:Insulin; D007378:Interleukins; D020738:Leptin