Strain-specific gut microbial signatures in type 2 diabetes identified in a cross-cohort analysis of 8,117 metagenomes

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Mei Z., Wang F., Bhosle A., Dong D., Mehta R., Ghazi A., Zhang Y., Liu Y., Rinott E., Ma S., Rimm E.B., Daviglus M., Willett W.C., Knight R., Hu F.B., Qi Q., Chan A.T., Burk R.D., Stampfer M.J., Shai I., Kaplan R.C., Huttenhower C., Wang D.D.
Journal
Nature medicine
Year
2024
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.

Experiment 1


Needs review

Curated date: 2025/10/12

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Subjects

Location of subjects
China
Denmark
Finland
France
Germany
Israel
Sweden
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to metformin Response to metformin,response to metformin
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Metformin naive T2D (type 2 diabetes) patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Metformin treated T2D (type 2 diabetes) patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Species confounded by metformin use in T2D (type 2 diabetes) cases
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
7

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina, Ion Torrent, BGISEQ-500 Sequencing

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
log transformation
Statistical test
MaAsLin2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.10
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/15

Curator: Tosin

Revision editor(s): Tosin

Source: Extended Data Figure 4B

Description: Meta-analyzed and cohort-specific associations of microbial species with metformin use among T2D (type 2 diabetes) patients

Abundance in Group 1: increased abundance in Metformin treated T2D (type 2 diabetes) patients

NCBI Quality ControlLinks
Acidaminococcus intestini
Bilophila wadsworthia

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/10/15

Curator: Tosin

Revision editor(s): Tosin

Source: Extended Data Figure 4B

Description: Meta-analyzed and cohort-specific associations of microbial species with metformin use among type 2 diabetes (T2D) patients

Abundance in Group 1: decreased abundance in Metformin treated T2D (type 2 diabetes) patients

NCBI Quality ControlLinks
Agathobacter rectalis
Dorea longicatena
Faecalibacterium prausnitzii
Firmicutes bacterium CAG:95
Fusicatenibacter saccharivorans
Intestinibacter bartlettii
Lachnospira eligens
Roseburia sp. CAG:309

Revision editor(s): Tosin

Experiment 2


Needs review

Curated date: 2025/10/15

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Metformin naive T2D patients
Group 1 name Corresponds to the case (exposed) group for case-control studies
Metformin treated T2D patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Species associated with both metformin use and T2D cases

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/15

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Fig. 4B

Description: Meta-analyzed and cohort-specific associations of microbial species associated with both metformin use and T2D

Abundance in Group 1: increased abundance in Metformin treated T2D patients

NCBI Quality ControlLinks
Escherichia coli
Enterocloster bolteae

Revision editor(s): Fiddyhamma

Signature 2

Needs review

Curated date: 2025/10/15

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Fig. 4B

Description: Meta-analyzed and cohort-specific associations of microbial species associated with both metformin use and T2D

Abundance in Group 1: decreased abundance in Metformin treated T2D patients

NCBI Quality ControlLinks
Roseburia sp. CAG:182
Clostridium sp. CAG:167

Revision editor(s): Fiddyhamma

Experiment 3


Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Diabetes mellitus Diabetes,diabetes,diabetes mellitus,diabetes mellitus (disease),Diabetes mellitus (disorder),Diabetes mellitus, NOS,Diabetes NOS,DM,DM - Diabetes mellitus,Diabetes mellitus
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Increased normoglycemic
Group 1 name Corresponds to the case (exposed) group for case-control studies
Decreased normoglycemic
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People with decreasing normoglycemic condition, which finalizes in type 2 diabetes (diabetes mellitus).
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex


Signature 1

Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 2a and Supplementary Table 3

Description: Heatmap for the meta-analyzed associations of microbial species with T2D. The blue-to-red gradient represents the magnitude and direction of the associations quantified by a linear mixed model that includes disease status as an ordinal variable (normoglycemic controls, prediabetes or T2D) and adjust for age, sex, FDR with a target of 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Acidaminococcus intestini
Anaerotruncus colihominis
Bacteroides fragilis
Bacteroides thetaiotaomicron
Bifidobacterium bifidum
Bilophila wadsworthia
Collinsella aerofaciens
Dorea formicigenerans
Eisenbergiella massiliensis
Escherichia coli
Flavonifractor plautii
Megamonas funiformis
Megasphaera elsdenii
Phascolarctobacterium faecium
Streptococcus anginosus group
Streptococcus gordonii
Streptococcus parasanguinis
Streptococcus salivarius
Enterocloster bolteae
Enterocloster citroniae
Blautia sp. CAG:257
Dorea sp. CAG:317
Mediterraneibacter gnavus

Revision editor(s): YokoC

Signature 2

Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 2a and Supplementary Table 3

Description: Heatmap for the meta-analyzed associations of microbial species with T2D. The blue-to-red gradient represents the magnitude and direction of the associations quantified by a linear mixed model that includes disease status as an ordinal variable (normoglycemic controls, prediabetes or T2D) and adjust for age, sex, FDR with a target of 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Alistipes inops
Alistipes onderdonkii
Alistipes putredinis
Alistipes shahii
Anaeromassilibacillus sp. An250
Anaerostipes hadrus
Barnesiella intestinihominis
Coprobacter secundus
Coprococcus eutactus
Desulfovibrio piger
Dorea longicatena
Faecalibacterium prausnitzii
Fusicatenibacter saccharivorans
Intestinibacter bartlettii
Methanobrevibacter smithii
Parasutterella excrementihominis
Roseburia faecis
Roseburia intestinalis
Ruminococcaceae bacterium D5
Turicibacter sanguinis
Victivallis vadensis
Bacteroides sp. CAG:144
Eubacterium sp. CAG:38
Firmicutes bacterium CAG:110
Phocaeicola plebeius
Firmicutes bacterium CAG:94
Firmicutes bacterium CAG:170
Clostridium sp. CAG:253
Oscillibacter sp. CAG:241
Ruminococcus bicirculans (ex Liu et al. 2021)
[Ruminococcus] lactaris
Oscillibacter sp. 57_20
[Eubacterium] siraeum
Firmicutes bacterium CAG:95
Eshraghiella crossota
Lachnospira eligens
Roseburia sp. CAG:309
Firmicutes bacterium CAG:238
Clostridium sp. CAG:167
Roseburia sp. CAG:182

Revision editor(s): YokoC

Experiment 4


Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex


Signature 1

Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 2a and Supplementary Table 3

Description: Heatmap for the meta-analyzed associations of microbial species with T2D. The blue-to-red gradient represents the magnitude and direction of the associations quantified by a linear mixed model that includes disease status as an ordinal variable (normoglycemic controls, prediabetes or T2D) and adjust for age, sex, FDR with a target of 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Acidaminococcus intestini
Streptococcus salivarius
Bacteroides thetaiotaomicron
Phascolarctobacterium faecium
Mediterraneibacter gnavus
Bifidobacterium bifidum
Intestinimonas butyriciproducens
Streptococcus parasanguinis
Eisenbergiella massiliensis
Bacteroides fragilis
Blautia sp. CAG:257
Bilophila wadsworthia
Anaerotruncus colihominis
Flavonifractor plautii
Streptococcus gordonii
Enterocloster bolteae
Enterocloster citroniae
Streptococcus anginosus group
Escherichia coli

Revision editor(s): YokoC

Signature 2

Needs review

Curated date: 2025/10/16

Curator: YokoC

Revision editor(s): YokoC

Source: Figure 2a and Supplementary Table 3

Description: Heatmap for the meta-analyzed associations of microbial species with T2D. The blue-to-red gradient represents the magnitude and direction of the associations quantified by a linear mixed model that includes disease status as an ordinal variable (normoglycemic controls, prediabetes or T2D) and adjust for age, sex, FDR with a target of 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Alistipes shahii
Barnesiella intestinihominis
Clostridium sp. CAG:167
Clostridium sp. CAG:253
Coprococcus eutactus
Desulfovibrio piger
Dorea longicatena
Eshraghiella crossota
Faecalibacterium prausnitzii
Firmicutes bacterium CAG:170
Firmicutes bacterium CAG:238
Firmicutes bacterium CAG:95
Fusicatenibacter saccharivorans
Intestinibacter bartlettii
Lachnospira eligens
Oscillibacter sp. 57_20
Oscillibacter sp. CAG:241
Parasutterella excrementihominis
Phocaeicola plebeius
Roseburia faecis
Roseburia intestinalis
Roseburia sp. CAG:182
Roseburia sp. CAG:309
Ruminococcus bicirculans (ex Liu et al. 2021)
Turicibacter sanguinis
[Ruminococcus] lactaris
Agathobacter rectalis

Revision editor(s): YokoC

Experiment 5


Needs review

Curated date: 2025/10/16

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 diabetes (T2D)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People with type 2 diabetes (diabetes mellitus).
Group 0 sample size Number of subjects in the control (unexposed) group
2277
Group 1 sample size Number of subjects in the case (exposed) group
1851

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex


Signature 1

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: increased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Acidaminococcus intestini
Anaerotignum lactatifermentans
Anaerotruncus colihominis
Bacteroides fragilis
Bacteroides thetaiotaomicron
Bifidobacterium bifidum
Bilophila wadsworthia
Blautia sp. CAG:257
Dorea sp. CAG:317
Enterocloster bolteae
Enterocloster citroniae
Enterocloster lavalensis
Escherichia coli
Flavonifractor plautii
Mediterraneibacter gnavus
Megamonas funiformis
Streptococcus anginosus group
Streptococcus gordonii
Streptococcus parasanguinis
Streptococcus salivarius
Thomasclavelia ramosa
[Clostridium] symbiosum

Revision editor(s): Fiddyhamma

Signature 2

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Source: Extended Data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Alistipes inops
Alistipes putredinis
Alistipes shahii
Anaeromassilibacillus sp. An250
Anaerostipes hadrus
Bacteroides sp. CAG:144
Barnesiella intestinihominis
Bifidobacterium longum
Clostridium sp. CAG:167
Clostridium sp. CAG:253
Coprobacter secundus
Coprococcus eutactus
Dorea longicatena
Eshraghiella crossota
Faecalibacterium prausnitzii
Firmicutes bacterium CAG:110
Firmicutes bacterium CAG:170
Firmicutes bacterium CAG:238
Firmicutes bacterium CAG:94
Firmicutes bacterium CAG:95
Fusicatenibacter saccharivorans
Lachnospira eligens
Methanobrevibacter smithii
Odoribacter splanchnicus
Oscillibacter sp. 57_20
Oscillibacter sp. CAG:241
Parasutterella excrementihominis
Phocaeicola plebeius
Roseburia faecis
Roseburia hominis
Roseburia intestinalis
Roseburia sp. CAG:182
Roseburia sp. CAG:309
Ruminococcaceae bacterium D5
Victivallis vadensis
[Eubacterium] siraeum
[Ruminococcus] lactaris
Ruminococcus bicirculansRuminococcus bicirculans

Revision editor(s): Tosin, Fiddyhamma

Experiment 6


Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex


Signature 1

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: increased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Acidaminococcus intestini
Bacteroides fragilis
Bacteroides thetaiotaomicron
Bifidobacterium bifidum
Bilophila wadsworthia
Coprococcus catus
Enterocloster bolteae
Enterocloster citroniae
Escherichia coli
Flavonifractor plautii
Streptococcus anginosus group
Streptococcus gordonii
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Fiddyhamma

Signature 2

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Source: Extended Data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Alistipes inops
Anaerostipes hadrus
Barnesiella intestinihominis
Clostridium sp. CAG:167
Clostridium sp. CAG:253
Coprococcus eutactus
Dorea longicatena
Eshraghiella crossota
Faecalibacterium prausnitzii
Firmicutes bacterium CAG:238
Firmicutes bacterium CAG:95
Fusicatenibacter saccharivorans
Lachnospira eligens
Oscillibacter sp. 57_20
Parasutterella excrementihominis
Phocaeicola plebeius
Roseburia faecis
Roseburia intestinalis
Roseburia sp. CAG:182
Roseburia sp. CAG:309
[Ruminococcus] lactaris

Revision editor(s): Tosin, Fiddyhamma

Experiment 7


Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: increased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Acidaminococcus intestini
Bacteroides fragilis
Bifidobacterium bifidum
Dorea sp. CAG:317
Enterocloster bolteae
Enterocloster citroniae
Escherichia coli
Flavonifractor plautii
Holdemania filiformis
Streptococcus parasanguinis
Streptococcus salivarius
Thomasclavelia ramosa

Revision editor(s): Fiddyhamma

Signature 2

Needs review

Curated date: 2025/10/21

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Source: Extended Data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Alistipes inops
Alistipes putredinis
Alistipes shahii
Clostridium sp. CAG:167
Coprobacter secundus
Coprococcus eutactus
Eshraghiella crossota
Firmicutes bacterium CAG:110
Firmicutes bacterium CAG:238
Firmicutes bacterium CAG:95
Fusicatenibacter saccharivorans
Odoribacter splanchnicus
Oscillibacter sp. 57_20
Parasutterella excrementihominis
Roseburia sp. CAG:182
Roseburia sp. CAG:309
Victivallis vadensis
[Ruminococcus] lactaris

Revision editor(s): Tosin, Fiddyhamma

Experiment 8


Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.

Abundance in Group 1: increased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Bacteroides fragilis
Bifidobacterium bifidum
Dorea sp. CAG:317
Enterocloster citroniae
Escherichia coli
Flavonifractor plautii
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Fiddyhamma

Experiment 9


Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use, Confounders controlled for: "insulin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.insulin use


Signature 1

Needs review

Curated date: 2025/10/17

Curator: Fiddyhamma

Revision editor(s): Fiddyhamma

Source: Extended data Figure 3B and Supplementary Table 2

Description: Meta- analyzed associations of individual microbial species with type 2 diabetes (T2D) phenotype from the binary (b) models.The binary model modeled the disease status as a binary variable (T2D or controls) and used data from T2D patients and normoglycemic controls.         

Abundance in Group 1: increased abundance in Type 2 diabetes (T2D)

NCBI Quality ControlLinks
Dorea sp. CAG:317
Escherichia coli
Flavonifractor plautii
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Fiddyhamma

Experiment 10


Needs review

Curated date: 2025/10/18

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Increased normoglycemic (ordinal model)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Decreased normoglycemic (ordinal model)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People with decreasing normoglycemic condition, which finalizes in type 2 diabetes (T2D) mellitus
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
10

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/18

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 2A, Extended Data Figure 3A and Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex, body mass index (BMI), and metformin use (metf). For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Bacteroides fragilis
Enterocloster bolteae
Enterocloster citroniae
Escherichia coli
Flavonifractor plautii
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/10/18

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 2A, Extended Data Figure 3A and Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex, body mass index (BMI), and metformin use (metf). For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Clostridium sp. CAG:167
Coprococcus eutactus
Desulfovibrio piger
Firmicutes bacterium CAG:238
Oscillibacter sp. 57_20
Roseburia sp. CAG:182
Turicibacter sanguinis

Revision editor(s): Tosin

Experiment 11


Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People with decreasing normoglycemic condition, which finalizes in type 2 diabetes (diabetes mellitus).

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use, Confounders controlled for: "insulin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.insulin use


Signature 1

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin

Source: Extended Data Figure 3A, Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex, body mass index (BMI),metformin use (metf) and insulin use. For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Bacteroides fragilis
Enterocloster bolteae
Enterocloster citroniae
Escherichia coli
Flavonifractor plautii
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Tosin

Signature 2

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin

Source: Extended Data Figure 3A, Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex, body mass index (BMI),metformin use (metf) and insulin use. For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Clostridium sp. CAG:167
Coprococcus eutactus
Desulfovibrio piger
Firmicutes bacterium CAG:238
Oscillibacter sp. 57_20
Roseburia sp. CAG:182
Turicibacter sanguinis

Revision editor(s): Tosin

Experiment 12


Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
People with decreasing normoglycemic condition, which finalizes in type 2 diabetes (T2D) mellitus

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin, Fiddyhamma

Source: Figure 2A, Extended Data Figure 3A and Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex and metformin use (metf). For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Anaerotruncus colihominis
Bacteroides fragilis
Blautia sp. CAG:257
Clostridium sp. CAG:58
Collinsella aerofaciens
Dorea sp. CAG:317
Eisenbergiella massiliensis
Enterocloster bolteae
Enterocloster citroniae
Escherichia coli
Eubacterium ventriosum
Flavonifractor plautii
Megamonas funiformis
Streptococcus anginosus group
Streptococcus parasanguinis
Streptococcus salivarius

Revision editor(s): Tosin, Fiddyhamma

Signature 2

Needs review

Curated date: 2025/10/20

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 2A, Extended Data Figure 3A and Supplementary Table 3

Description: Meta-analyzed associations of microbial species with type 2 diabetes (T2D) based on 8,117 metagenomes from 1,851 T2D patients, 2,770 individuals with prediabetes, and 2,277 normoglycemic controls. The blue-to-red gradient represents the magnitude and direction of the associations quantified by linear mixed models that include disease status as an ordinal variable (normoglycemic controls, prediabetes, or T2D) and adjust for age, sex and metformin use (metf). For multiple comparison correction, we controlled the false discovery rate (FDR) with a target rate of 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic (ordinal model)

NCBI Quality ControlLinks
Alistipes putredinis
Alistipes shahii
Barnesiella intestinihominis
Clostridium sp. CAG:167
Coprobacter secundus
Coprococcus eutactus
Desulfovibrio piger
Eshraghiella crossota
Faecalibacterium prausnitzii
Firmicutes bacterium CAG:110
Firmicutes bacterium CAG:238
Firmicutes bacterium CAG:95
Lachnospira eligens
Methanobrevibacter smithii
Odoribacter splanchnicus
Oscillibacter sp. 57_20
Parasutterella excrementihominis
Phocaeicola plebeius
Roseburia sp. CAG:182
Roseburia sp. CAG:309
Ruminococcaceae bacterium D5
Turicibacter sanguinis
Victivallis vadensis
[Ruminococcus] lactaris

Revision editor(s): Tosin

Experiment 13


Needs review

Curated date: 2025/10/20

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Increased normoglycemic
Group 1 name Corresponds to the case (exposed) group for case-control studies
Decreased normoglycemic
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female patients with type 2 diabetes (diabetes mellitus), from a model where the disease status was treated as an ordinal variable (type 2 diabetes, prediabetic, normoglycemic controls).

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, Confounders controlled for: "metformin use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.metformin use


Signature 1

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an ordinal variable (normoglycemic controls, prediabetes or T2D). FDR < 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Escherichia coli

Revision editor(s): YokoC

Signature 2

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an ordinal variable (normoglycemic controls, prediabetes or T2D). FDR < 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Clostridium sp. CAG:167

Revision editor(s): YokoC

Experiment 14


Needs review

Curated date: 2025/10/20

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic (control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
T2D (type 2 diabetes)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Female patients with type 2 diabetes (diabetes mellitus) from a binomial model (type 2 diabetes and normoglycemic controls).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an binomial variable (normoglycemic controls or T2D). FDR < 0.10.

Abundance in Group 1: increased abundance in T2D (type 2 diabetes)

NCBI Quality ControlLinks
Escherichia coli

Revision editor(s): YokoC

Experiment 15


Needs review

Curated date: 2025/10/20

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Increased normoglycemic
Group 1 name Corresponds to the case (exposed) group for case-control studies
Decreased normoglycemic
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Male patients with type 2 diabetes (diabetes mellitus), from a model where the disease status was treated as an ordinal variable (type 2 diabetes, prediabetic, normoglycemic controls).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an ordinal variable (normoglycemic controls, prediabetes or T2D). FDR < 0.10.

Abundance in Group 1: increased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
Anaerotruncus colihominis
Collinsella aerofaciens
Enterocloster asparagiformis
Enterocloster bolteae
Enterocloster citroniae
Eubacterium ventriosum
Flavonifractor plautii

Revision editor(s): YokoC

Signature 2

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an ordinal variable (normoglycemic controls, prediabetes or T2D). FDR < 0.10.

Abundance in Group 1: decreased abundance in Decreased normoglycemic

NCBI Quality ControlLinks
marine bacterium JAMB33
Oscillibacter sp. 57_20
Clostridium sp. CAG:253
Desulfovibrio piger

Revision editor(s): YokoC

Experiment 16


Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic (control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
T2D (type 2 diabetes)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Male patients with type 2 diabetes (diabetes mellitus), from a model where the disease status was treated as a binomial variable (type 2 diabetes or normoglycemic controls).

Lab analysis

Statistical Analysis

Signature 1

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Heatmap of meta-analyzed associations of microbial species with T2D (type 2 diabetes). The blue-to-red gradient represents the magnitude and direction of the associations quantified by Maaslin2, where the disease status is an binomial variable (normoglycemic controls or T2D). FDR < 0.10.

Abundance in Group 1: increased abundance in T2D (type 2 diabetes)

NCBI Quality ControlLinks
Enterocloster citroniae

Revision editor(s): YokoC

Signature 2

Needs review

Curated date: 2025/10/21

Curator: YokoC

Revision editor(s): YokoC

Source: Supplementary Table 11

Description: Male patients with type 2 diabetes (diabetes mellitus), from a model where the disease status was treated as a binomial variable (type 2 diabetes or normoglycemic controls).

Abundance in Group 1: decreased abundance in T2D (type 2 diabetes)

NCBI Quality ControlLinks
Firmicutes bacterium CAG:238
Coprococcus eutactus CAG:665

Revision editor(s): YokoC