title: Gut metagenome in European women with normal, impaired and diabetic glucose control.
abstract: Type 2 diabetes (T2D) is a result of complex gene-environment interactions, and several risk factors have been identified, including age, family history, diet, sedentary lifestyle and obesity. Statistical models that combine known risk factors for T2D can partly identify individuals at high risk of developing the disease. However, these studies have so far indicated that human genetics contributes little to the models, whereas socio-demographic and environmental factors have greater influence. Recent evidence suggests the importance of the gut microbiota as an environmental factor, and an altered gut microbiota has been linked to metabolic diseases including obesity, diabetes and cardiovascular disease. Here we use shotgun sequencing to characterize the faecal metagenome of 145 European women with normal, impaired or diabetic glucose control. We observe compositional and functional alterations in the metagenomes of women with T2D, and develop a mathematical model based on metagenomic profiles that identified T2D with high accuracy. We applied this model to women with impaired glucose tolerance, and show that it can identify women who have a diabetes-like metabolism. Furthermore, glucose control and medication were unlikely to have major confounding effects. We also applied our model to a recently described Chinese cohort and show that the discriminant metagenomic markers for T2D differ between the European and Chinese cohorts. Therefore, metagenomic predictive tools for T2D should be specific for the age and geographical location of the populations studied.
authors.affiliation: Department of Chemical and Biological Engineering, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
authors.forename: Fredrik H
authors.initials: FH
authors.lastname: Karlsson
authors.forename: Valentina
authors.initials: V
authors.lastname: Tremaroli
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.forename: Carl Johan
authors.initials: CJ
authors.lastname: Behre
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.forename: Fredrik
authors.initials: F
authors.lastname: Bäckhed
mesh_terms: D000367:Age Factors; D000368:Aged; D044466:Asian People; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism*; D016000:Cluster Analysis; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000382:microbiology*; D004777:Environment; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D018149:Glucose Intolerance / Q000097:blood / Q000378:metabolism / Q000382:microbiology*; D006262:Health; D006801:Humans; D054892:Metagenome / Q000235:genetics; D008875:Middle Aged; D008954:Models, Biological; D011379:Prognosis; D013045:Species Specificity; D013548:Sweden; D044465:White People
chemical_list: D015415:Biomarkers; D001786:Blood Glucose