A metagenome-wide association study of gut microbiota in type 2 diabetes

Nature. 2012 Oct 4;490(7418):55-60. doi: 10.1038/nature11450. Epub 2012 Sep 26.

Abstract

Assessment and characterization of gut microbiota has become a major research area in human disease, including type 2 diabetes, the most prevalent endocrine disease worldwide. To carry out analysis on gut microbial content in patients with type 2 diabetes, we developed a protocol for a metagenome-wide association study (MGWAS) and undertook a two-stage MGWAS based on deep shotgun sequencing of the gut microbial DNA from 345 Chinese individuals. We identified and validated approximately 60,000 type-2-diabetes-associated markers and established the concept of a metagenomic linkage group, enabling taxonomic species-level analyses. MGWAS analysis showed that patients with type 2 diabetes were characterized by a moderate degree of gut microbial dysbiosis, a decrease in the abundance of some universal butyrate-producing bacteria and an increase in various opportunistic pathogens, as well as an enrichment of other microbial functions conferring sulphate reduction and oxidative stress resistance. An analysis of 23 additional individuals demonstrated that these gut microbial markers might be useful for classifying type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian Continental Ancestry Group
  • Butyrates / metabolism
  • China / ethnology
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / classification
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / microbiology*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Feces / microbiology
  • Genetic Linkage / genetics
  • Genetic Markers
  • Genome-Wide Association Study / methods*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intestines / microbiology*
  • Metabolic Networks and Pathways / genetics
  • Metagenome / genetics*
  • Metagenomics / methods*
  • Opportunistic Infections / complications
  • Opportunistic Infections / microbiology
  • Reference Standards
  • Sulfates / metabolism

Substances

  • Butyrates
  • Genetic Markers
  • Sulfates