title: Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism.
abstract: Circadian clocks and metabolism are inextricably intertwined, where central and hepatic circadian clocks coordinate metabolic events in response to light-dark and sleep-wake cycles. We reveal an additional key element involved in maintaining host circadian rhythms, the gut microbiome. Despite persistence of light-dark signals, germ-free mice fed low or high-fat diets exhibit markedly impaired central and hepatic circadian clock gene expression and do not gain weight compared to conventionally raised counterparts. Examination of gut microbiota in conventionally raised mice showed differential diurnal variation in microbial structure and function dependent upon dietary composition. Additionally, specific microbial metabolites induced under low- or high-fat feeding, particularly short-chain fatty acids, but not hydrogen sulfide, directly modulate circadian clock gene expression within hepatocytes. These results underscore the ability of microbially derived metabolites to regulate or modify central and hepatic circadian rhythm and host metabolic function, the latter following intake of a Westernized diet.
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.affiliation: Institute for Genomics and Systems Biology, Argonne, IL 60439, USA; Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Gibbons
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Martinez
authors.affiliation: Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Hutchison
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Edmond Y
authors.initials: EY
authors.lastname: Huang
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Candace M
authors.initials: CM
authors.lastname: Cham
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Pierre
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Heneghan
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Anuradha
authors.initials: A
authors.lastname: Nadimpalli
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Hubert
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zale
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Surgery, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Theriault
authors.affiliation: Graduate Program in Biophysical Sciences, The University of Chicago, Chicago, IL 60637, USA; James Frank Institute, The University of Chicago, Chicago, IL 60637, USA; Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Dinner
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.affiliation: Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Kudsk
authors.affiliation: Institute for Mind and Biology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Prendergast
authors.affiliation: Institute for Genomics and Systems Biology, Argonne, IL 60439, USA; Department of Ecology and Evolution, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jack A
authors.initials: JA
authors.lastname: Gilbert
authors.affiliation: Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address: echang@medicine.bsd.uchicago.edu.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
mesh_terms: D000818:Animals; D001835:Body Weight; D057906:Circadian Clocks; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000139:chemically induced*; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D020869:Gene Expression Profiling; D050356:Lipid Metabolism; D008099:Liver / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity; D017422:Sequence Analysis, DNA