title: Human gut microbes impact host serum metabolome and insulin sensitivity.
abstract: Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.
authors.forename: Helle Krogh
authors.initials: HK
authors.lastname: Pedersen
authors.forename: Valborg
authors.initials: V
authors.lastname: Gudmundsdottir
authors.forename: Henrik Bjørn
authors.initials: HB
authors.lastname: Nielsen
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyotylainen
authors.forename: Trine
authors.initials: T
authors.lastname: Nielsen
authors.forename: Benjamin A H
authors.initials: BA
authors.lastname: Jensen
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Forslund
authors.forename: Falk
authors.initials: F
authors.lastname: Hildebrand
authors.forename: Edi
authors.initials: E
authors.lastname: Prifti
authors.forename: Gwen
authors.initials: G
authors.lastname: Falony
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Le Chatelier
authors.forename: Florence
authors.initials: F
authors.lastname: Levenez
authors.forename: Joel
authors.initials: J
authors.lastname: Doré
authors.forename: Ismo
authors.initials: I
authors.lastname: Mattila
authors.forename: Damian R
authors.initials: DR
authors.lastname: Plichta
authors.forename: Päivi
authors.initials: P
authors.lastname: Pöhö
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.forename: Manimozhiyan
authors.initials: M
authors.lastname: Arumugam
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sunagawa
authors.forename: Sara
authors.initials: S
authors.lastname: Vieira-Silva
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Jacob Bak
authors.initials: JB
authors.lastname: Holm
authors.forename: Kajetan
authors.initials: K
authors.lastname: Trošt
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: S Dusko
authors.initials: SD
authors.lastname: Ehrlich
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D001439:Bacteroides / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000382:microbiology; D005215:Fasting / Q000097:blood / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D018149:Glucose Intolerance / Q000097:blood / Q000382:microbiology; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D055442:Metabolome; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D009426:Netherlands; D018720:Prevotella / Q000502:physiology; D044967:Serum / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain