Faculty Collaboration Database

Longitudinal multi-omics of host-microbe dynamics in prediabetes. Nature 2019 May;569(7758):663-671

Date

05/31/2019

Pubmed ID

31142858

Pubmed Central ID

PMC6666404

DOI

10.1038/s41586-019-1236-x

Scopus ID

2-s2.0-85066507489 (requires institutional sign-in at Scopus site)   400 Citations

Abstract

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

Author List

Zhou W, Sailani MR, Contrepois K, Zhou Y, Ahadi S, Leopold SR, Zhang MJ, Rao V, Avina M, Mishra T, Johnson J, Lee-McMullen B, Chen S, Metwally AA, Tran TDB, Nguyen H, Zhou X, Albright B, Hong BY, Petersen L, Bautista E, Hanson B, Chen L, Spakowicz D, Bahmani A, Salins D, Leopold B, Ashland M, Dagan-Rosenfeld O, Rego S, Limcaoco P, Colbert E, Allister C, Perelman D, Craig C, Wei E, Chaib H, Hornburg D, Dunn J, Liang L, Rose SMS, Kukurba K, Piening B, Rost H, Tse D, McLaughlin T, Sodergren E, Weinstock GM, Snyder M

Author

Liang Liang PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Anti-Bacterial Agents
Biomarkers
Cohort Studies
Computational Biology
Datasets as Topic
Diabetes Mellitus, Type 2
Female
Gastrointestinal Microbiome
Glucose
Healthy Volunteers
Humans
Inflammation
Influenza Vaccines
Insulin
Insulin Resistance
Longitudinal Studies
Male
Microbiota
Middle Aged
Prediabetic State
Proteome
Respiratory Tract Infections
Stress, Physiological
Transcriptome
Vaccination