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Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes.
Mei, Zhendong; Wang, Fenglei; Bhosle, Amrisha; Dong, Danyue; Mehta, Raaj; Ghazi, Andrew; Zhang, Yancong; Liu, Yuxi; Rinott, Ehud; Ma, Siyuan; Rimm, Eric B; Daviglus, Martha; Willett, Walter C; Knight, Rob; Hu, Frank B; Qi, Qibin; Chan, Andrew T; Burk, Robert D; Stampfer, Meir J; Shai, Iris; Kaplan, Robert C; Huttenhower, Curtis; Wang, Dong D.
Affiliation
  • Mei Z; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Wang F; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bhosle A; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dong D; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Mehta R; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ghazi A; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Zhang Y; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Liu Y; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Rinott E; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ma S; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Rimm EB; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Daviglus M; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
  • Willett WC; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Knight R; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Hu FB; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Qi Q; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Chan AT; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Burk RD; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Stampfer MJ; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Shai I; Department of Medicine, Hebrew University and Hadassah Medical Center, Jerusalem, Israel.
  • Kaplan RC; Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Huttenhower C; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Wang DD; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Nat Med ; 30(8): 2265-2276, 2024 Aug.
Article in En | MEDLINE | ID: mdl-38918632
ABSTRACT
The association of gut microbial features with type 2 diabetes (T2D) has been inconsistent due in part to the complexity of this disease and variation in study design. Even in cases in which individual microbial species have been associated with T2D, mechanisms have been unable to be attributed to these associations based on specific microbial strains. We conducted a comprehensive study of the T2D microbiome, analyzing 8,117 shotgun metagenomes from 10 cohorts of individuals with T2D, prediabetes, and normoglycemic status in the United States, Europe, Israel and China. Dysbiosis in 19 phylogenetically diverse species was associated with T2D (false discovery rate < 0.10), for example, enriched Clostridium bolteae and depleted Butyrivibrio crossotus. These microorganisms also contributed to community-level functional changes potentially underlying T2D pathogenesis, for example, perturbations in glucose metabolism. Our study identifies within-species phylogenetic diversity for strains of 27 species that explain inter-individual differences in T2D risk, such as Eubacterium rectale. In some cases, these were explained by strain-specific gene carriage, including loci involved in various mechanisms of horizontal gene transfer and novel biological processes underlying metabolic risk, for example, quorum sensing. In summary, our study provides robust cross-cohort microbial signatures in a strain-resolved manner and offers new mechanistic insights into T2D.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phylogeny / Diabetes Mellitus, Type 2 / Metagenome / Gastrointestinal Microbiome Limits: Female / Humans / Male / Middle aged Country/Region as subject: America do norte / Asia / Europa Language: En Journal: Nat Med Year: 2024 Document type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Phylogeny / Diabetes Mellitus, Type 2 / Metagenome / Gastrointestinal Microbiome Limits: Female / Humans / Male / Middle aged Country/Region as subject: America do norte / Asia / Europa Language: En Journal: Nat Med Year: 2024 Document type: Article