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

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.

Subspecies in the global human gut microbiome

“…Indeed, we found five species with significant subspecies associations with microbial community diversity and two with host body mass index (BMI) (FDR‐corrected P ‐value < 0.05, accounting for variation between studies; Table EV8 and Materials and Methods). In addition to these global associations, separate statistical tests within each study cohort revealed a strong negative association between type 2 diabetes status specifically in Chinese individuals (Qin et al , 2012) and Bacteroides coprocola MGSS3 , which is enriched in healthy individuals (Fisher test P ‐value 2.98e‐05). This association was, however, not significant in the two type 2 diabetes case–control studies with smaller cohorts (Karlsson et al , 2013; Le Chatelier et al , 2013).…”

“…To this end, we assessed the microbial genetic landscape of 2,144 deeply sequenced human stool metagenomes from nine countries, spanning three continents, including published (Huttenhower et al , 2012; Qin et al , 2012; Karlsson et al , 2013; Le Chatelier et al , 2013; Zeller et al , 2014) as well as 298 newly generated ones (Table EV1). The newly sequenced samples include a Kazakh cohort as well as three individuals from Germany that have been sampled over an extended period of time (see Materials and Methods).…”

“…Specifically, we used 239 stool samples from the HMP (Huttenhower et al , 2012) collected from 139 US American individuals, as well as 676 oral samples from the same individuals; 156 samples from as many Austrian individuals (Yu et al , 2015); 368 Chinese samples (Qin et al , 2012); 387 Danish samples from the MetaHIT cohort; 156 French and 40 German samples (Zeller et al , 2014); 126 novel German samples collected from 26 individuals; 172 novel Kazakh samples from 86 individuals; 359 Spanish samples from MetaHIT; and 145 Swedish samples (Karlsson et al , 2013; Table EV1). Informed consent was obtained from the German individuals through the my.microbes project (http://my.microbes.eu).…”

Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes

“…Case-control studies have associated microbial traits in individuals with patterns of diseases, thereby implicating gastrointestinal microbial communities in a range of human disorders [6][7][8][9][10] . Metagenomics is able to resolve differences in the functional potential of microbial communities and has revealed a surprisingly stable set of core functions, even though gastrointestinal community structures display great inter-individual variation 2 .…”

Ligature‐associated bacterial profiles are linked to type 2 diabetes mellitus in a rat model and influenced by antibody treatment against TNF‐α or RAGE

“…(Ellerin, Rubin, & Weinblatt, 2003). Furthermore, T2D has been reported to associate with an altered microbiological profile in the gut of humans, and this change has been proposed essential for the development of T2D (Qin et al, 2012). In line, in an animal study of female ZOR, the glycemic status was demonstrated to have an impact on the microbiota in the caecum with increased number of lactobacilli, which is parallel to the findings in the present study of the oral bacterial profile (Romo‐Vaquero et al, 2014).…”