A metagenome-wide association study of gut microbiota in type 2 diabetes
Open accessAbstract
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.
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Chronic low-grade metabolic inflammation (meta-inflammation) is a result of an imbalanced gut microbiome that promotes the development of insulin resistance and type 2 diabetes.
“Chronic low-grade ‘metabolic’ inflammation, or meta-inflammation, is a result of an imbalanced gut microbiome that promotes the development of insulin resistance and type 2 diabetes [135,136,137].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [137]
Akkermansia muciniphila is beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes.
“Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia and has been shown to be beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes (Grander et al., 2018; Qin et al., 2012).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Qin et al., 2012
Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia.
“Akkermansia muciniphila is the only isolated member of the phylum Verrucomicrobia and has been shown to be beneficial in metabolic and immune disorders by degrading mucin, which can be used as nutrients by enterocytes or other intestinal commensal microbes (Grander et al., 2018; Qin et al., 2012).”
From <i>Akkermansia muciniphila</i> alleviates <scp>high‐fat‐diet</scp> ‐related metabolic‐associated fatty liver disease by modulating gut microbiota and bile acids (2023) · cites this paper as Qin et al., 2012
The microbiome of T2D patients is markedly different from healthy individuals and is believed to promote inflammatory events by two distinct mechanisms.
“The microbiome of patients suffering from T2D, which is also markedly different from healthy individuals, is believed to promote these inflammatory events by two distinct mechanisms (Karlsson et al., 2013; Qin et al., 2012).”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Qin et al., 2012
Short chain fatty acids are produced by microbiota from dietary fibers, affect host body energy homeostasis, and are protective against metabolic syndrome, type 2 diabetes mellitus, and atherosclerosis.
“Short chain fatty acids are produced by microbiota from dietary fibers, effect host body energy homeostasis, and are protective against metabolic syndrome, type 2 diabetes mellitus, and atherosclerosis.15,45–47”
From The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids (2015) · cites this paper as [46]
In two (meta)genome-wide association studies, de novo generated metagenomic species-level gene clusters could better differentiate patients and controls with higher specificity than analysis based on human genome variation or other known risk factors such as BMI and waist circumference.
“In both studies, de novo generated metagenomic species-level gene clusters were employed as discriminant markers which, via mathematical modelling, could better differentiate between patients and controls with higher specificity than a similar analysis based on either human genome variation or other known risk factors such as BMI and waist circumference.”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [30]
Butyrate biosynthesis was decreased in the microbiota of patients in a metagenomic study.
“while butyrate biosynthesis was decreased.30”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [30]
Similar microbial metabolic shifts to those in IBD have been observed in other inflammatory conditions such as type 2 diabetes.
“similar microbial metabolic shifts have been observed in other inflammatory conditions such as T2D,30”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [30]
The similar microbial metabolic shifts observed in IBD and other inflammatory conditions suggest a common core gut microbial response to chronic inflammation and immune activation.
“suggesting a common core gut microbial response to chronic inflammation and immune activation.”
From The gut microbiota and host health: a new clinical frontier (2016) · cites this paper as [30]
A correlation between certain bacterial taxa and type 2 diabetes has been proposed based on analyses of human gut metagenomes.
“A correlation between certain bacterial taxa and type 2 diabetes has been proposed, based on analyses of human gut metagenomes [60, 61].”
From Antibiotic-Induced Changes in the Intestinal Microbiota and Disease (2016) · cites this paper as [61]
The microbes enriched in stroke and TIA patients were mainly opportunistic pathogens.
“the microbes that were enriched in stroke and TIA patients were mainly opportunistic pathogens, such as Enterobacter, Megasphaera, and Desulfovibrio.2, 3”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [2]
Faecalibacterium is a critical butyrate acid-producing beneficial bacterium that is reduced in many diseases.
“In particular, Faecalibacterium has been widely recognized as a critical butyrate acid–producing beneficial bacterium that is reduced in many diseases.2, 3, 23”
From Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack (2015) · cites this paper as [2]
Changes in the proportions of specific taxa of gut microbiota have been observed in various disease states including obesity, inflammatory bowel disease, type 1 and type 2 diabetes mellitus, biliary disease, and intestinal cancers.
“Changes in the proportions of specific taxa of gut microbiota have been observed in various disease states, including obesity68,69, inflammatory bowel disease70, type 1 and type 2 diabetes mellitus71,72, biliary disease73, and intestinal cancers74,75 among many others.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [72]
Numerous facets of GI microbial community composition and metabolism have been associated with various disease states, including CVD, obesity, diabetes, and features of metabolic syndrome.
“Numerous facets of GI microbial community composition and metabolism have been associated with various disease states, including CVD, obesity, diabetes, and features of metabolic syndrome[274,310–313].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [311]
Reduced microbial diversity is associated with inflammation, obesity, hypertension, and features of metabolic syndrome.
“while conversely, reduced microbial diversity is associated with inflammation, obesity, hypertension, and features of metabolic syndrome[311,313,318,319].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [311]
T2D is characterized by complex host-microbiome interactions.
“T2D is characterized by complex host–microbiome interactions81,82”
From The Integrative Human Microbiome Project (2019) · cites this paper as [82]
T2DM patients have a reduction in butyrate-producing bacterial species and lower levels of butyrate biosynthesis compared with non-diabetic controls.
“T2DM patients have been found to have a reduction in butyrate-producing bacterial species, and lower levels of butyrate biosynthesis when the microbiomes of T2DM patients are compared with those of non-diabetic controls [6].”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [6]
Differences in intestinal microbiota composition have been uncovered between healthy controls and those suffering from various diseases, including obesity, the metabolic syndrome, and type-2 diabetes mellitus.
“Differences in intestinal microbiota composition have been uncovered between healthy controls and those suffering from various diseases, including metabolic pathologies such as obesity, the metabolic syndrome and type-2 diabetes mellitus (T2DM) [4], [5], [6].”
From Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals (2016) · cites this paper as [6]
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References 36 · Cited by 6,762
- Authors
- Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., Lu, D., Wu, P., Dai, Y., Sun, X., Li, Z., Tang, A., Zhong, S., Li, X., Chen, W., Xu, R., Wang, M., Feng, Q., Gong, M., Yu, J., Zhang, Y., Zhang, M., Hansen, T., Sanchez, G., Raes, J., Falony, G., Okuda, S., Almeida, M., LeChatelier, E., Renault, P., Pons, N., Batto, J.-M., Zhang, Z., Chen, H., Yang, R., Zheng, W., Li, S., Yang, H., Wang, J., Ehrlich, S. D., Nielsen, R., Pedersen, O., Kristiansen, K., & Wang, J.
- Affiliations
- BGI Group (China) (CN)
- Shenzhen University (CN)
- Peking University Shenzhen Hospital (CN)
- Guangdong General Hospital (CN)
- University of Copenhagen (DK)
- University of California, Berkeley (US)
- Vrije Universiteit Brussel (BE)
- Microbiologie de l’alimentation au service de la santé (FR)
- Institut National de la Recherche Agronomique (FR)
- Corresponding author
- Wang, Jian
- Wang, Jun
- ORCID
- Qin, Junjie
- Li, Yingrui
- Cai, Zhiming
- Li, Shenghui
- Zhu, Jianfeng
- Zhang, Fan
- Liang, Suisha
- Zhang, Wenwei
- Guan, Yuanlin
- Peng, Yangqing
- Zhang, Dongya
- Jie, Zhuye
- Wu, Wenxian
- Qin, Youwen
- Li, Junhua
- Han, Lingchuan
- Sun, Xiaojuan
- Li, Zesong
- Zhong, Shilong
- Li, Xiaoping
- Wang, Mingbang
- Feng, Qiang
- Gong, Meihua
- Yu, Jing
- Zhang, Yanyan
- Zhang, Ming
- Hansen, Torben
- Raes, Jeroen
- Falony, Gwen
- Okuda, Shujiro
- Almeida, Mathieu
- Renault, Pierre
- Pons, Nicolas
- Zhang, Zhaoxi
- Chen, Hua
- Yang, Ruifu
- Li, Songgang
- Yang, Huanming
- Wang, Jian
- Ehrlich, S. Dusko
- Nielsen, Rasmus
- Pedersen, Oluf
- Kristiansen, Karsten
- Wang, Jun
- Venue
- Nature
- Published
- 2012-09-26
- Volume
- 490
- Issue
- 7418
- Pages
- 55-60
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2071841602
- Cited by
- 6,762
- References
- 36
- Citations by year
- 2026: 342 · 2025: 498 · 2024: 568 · 2023: 621 · 2022: 679 · 2021: 785 · 2020: 736 · 2019: 557 · 2018: 460 · 2017: 416 · 2016: 391 · 2015: 301 · 2014: 215 · 2013: 170 · 2012: 8
- FWCI
- 89.29
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Funders
- Agence Nationale de la Recherche (ANR-11-DPBS-0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- type 2 diabetes, gut microbiota, metagenome-wide association study, dysbiosis, butyrate-producing bacteria, opportunistic pathogens, sulfate reduction, oxidative stress resistance, fecal microbiota, biomarkers, Chinese population
- MeSH terms
- Butyrates, China, Diabetes Mellitus, Type 2, Feces, Genetic Markers, Humans, Intestines, Genetic Linkage, Opportunistic Infections, Reference Standards, Sulfates, Cohort Studies, Asian People, Metabolic Networks and Pathways, Metagenome, Genome-Wide Association Study, Metagenomics, High-Throughput Nucleotide Sequencing
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