Trans-ethnic gut microbiota signatures of type 2 diabetes in Denmark and India
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Alvarez-Silva C, Kashani A, Hansen TH, Pinna NK, Anjana RM, Dutta A, Saxena S, Støy J, Kampmann U, Nielsen T, Jørgensen T, Gnanaprakash V, Gnanavadivel R, Sukumaran A, Rani CSS, Færch K, Radha V, Balasubramanyam M, Nair GB, Das B, Vestergaard H, Hansen T, Mande SS, Mohan V, Arumugam M, Pedersen O
Journal
Genome medicine
Year
2021
Keywords:
Danes, Gut microbiota, Indians, Metformin, Populations, Trans-ethnic, Type 2 diabetes
BACKGROUND: Type 2 diabetes (T2D), a multifactorial disease influenced by host genetics and environmental factors, is the most common endocrine disease. Several studies have shown that the gut microbiota as a close-up environmental mediator influences host physiology including metabolism. The aim of the present study is to examine the compositional and functional potential of the gut microbiota across individuals from Denmark and South India with a focus on T2D. Many earlier studies have investigated the microbiome aspects of T2D, and it has also been anticipated that such microbial associations would be dependent on diet and ethnic origin. However, there has been no large scale trans-ethnic microbiome study earlier in this direction aimed at evaluating any "universal" microbiome signature of T2D. METHODS: 16S ribosomal RNA gene amplicon sequencing was performed on stool samples from 279 Danish and 294 Indian study participants. Any differences between the gut microbiota of both populations were explored using diversity measures and negative binomial Wald tests. Study samples were stratified to discover global and country-specific microbial signatures for T2D and treatment with the anti-hyperglycemic drug, metformin. To identify taxonomical and functional signatures of the gut microbiota for T2D and metformin treatment, we used alpha and beta diversity measures and differential abundances analysis, comparing metformin-naive T2D patients, metformin-treated T2D patients, and normoglycemic individuals. RESULTS: Overall, the gut microbial communities of Danes and Indians are compositionally very different. By analyzing the combined study materials, we identify microbial taxonomic and functional signatures for T2D and metformin treatment. T2D patients have an increased relative abundance of two operational taxonomic units (OTUs) from the Lachnospiraceae family, and a decreased abundance of Subdoligranulum and Butyricicoccus. Studying each population per se, we identified T2D-related microbial changes at the taxonomic level within the Danish population only. Alpha diversity indices show that there is no significant difference between normoglycemic individuals and metformin-naive T2D patients, whereas microbial richness is significantly decreased in metformin-treated T2D patients compared to metformin-naive T2D patients and normoglycemic individuals. Enrichment of two OTUs from Bacteroides and depletion of Faecalibacterium constitute a trans-ethnic signature of metformin treatment. CONCLUSIONS: We demonstrate major compositional differences of the gut microbiota between Danish and South Indian individuals, some of which may relate to differences in ethnicity, lifestyle, and demography. By comparing metformin-naive T2D patients and normoglycemic individuals, we identify T2D-related microbiota changes in the Danish and Indian study samples. In the present trans-ethnic study, we confirm that metformin changes the taxonomic profile and functional potential of the gut microbiota.
Experiment 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Subjects
- Location of subjects
- India
- 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 type 2 diabetes (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
- T2D patients treated with the anti-hyperglycemic drug, metformin
- Group 0 sample size Number of subjects in the control (unexposed) group
- 71
- Group 1 sample size Number of subjects in the case (exposed) group
- 86
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V1-V5
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Roche454
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- raw counts
- Statistical test
- DESeq2
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- 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
- age, body mass index, Confounders controlled for: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin, sex, proton-pump inhibitor
Alpha Diversity
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S11
Description: Differential abundant taxa between metformin-naive T2D and metformin-treated T2D in the Indian substudy
Abundance in Group 1: increased abundance in metformin-treated T2D patients
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnoclostridium |
Revision editor(s): ChiomaBlessing, Folakunmi
Experiment 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Differences from previous experiment shown
Subjects
- Location of subjects
- Denmark
- Group 0 sample size Number of subjects in the control (unexposed) group
- 61
- Group 1 sample size Number of subjects in the case (exposed) group
- 80
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 4 months
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex, proton-pump inhibitor, Confounders controlled for: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin
Alpha Diversity
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S10b
Description: Differential abundant taxa between metformin-naive T2D and metformin-treated T2D in the Danish substudy
Abundance in Group 1: increased abundance in metformin-treated T2D patients
| NCBI | Quality Control | Links |
|---|---|---|
| Escherichia/Shigella sp. |
Revision editor(s): ChiomaBlessing, Folakunmi
Experiment 3
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Population Population,population
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Indians (normoglycaemic controls and T2D patients)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Denmark (normoglycaemic controls and T2D patients)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Gut microbiota in Denmark participants
- Group 0 sample size Number of subjects in the control (unexposed) group
- 294
- Group 1 sample size Number of subjects in the case (exposed) group
- 279
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 4 months (Denmark participants)
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: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin, proton-pump inhibitor, sex
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S2b
Description: Differentially abundant taxa in the gut microbiome between Danes and Indians (normoglycaemic controls and T2D patients)
Abundance in Group 1: increased abundance in Denmark (normoglycaemic controls and T2D patients)
Revision editor(s): ChiomaBlessing, Joan Chuks
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S2b
Description: Differentially abundant taxa in the gut microbiome between Danes and Indians (normoglycaemic controls and T2D patients)
Abundance in Group 1: decreased abundance in Denmark (normoglycaemic controls and T2D patients)
Revision editor(s): ChiomaBlessing
Experiment 4
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Curated date: 2023/11/05
Curator: ChiomaBlessing
Revision editor(s): ChiomaBlessing, Folakunmi, Fiddyhamma
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Metformin 1,1-Dimethylbiguanide,C4H11N5,CN(C)C(=N)NC(N)=N,InChI=1/C4H11N5/c1-9(2)4(7)8-3(5)6/h1-2H3,(H5,5,6,7,8)/f/h5,7-8H,6H2,InChIKey=XZWYZXLIPXDOLR-WXQAPKLBCT,Metformin,N,N-dimethylimidodicarbonimidic diamide,metformin
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- metformin-naive type 2 diabetes (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
- T2D patients treated with the anti-hyperglycemic drug, metformin
- Group 0 sample size Number of subjects in the control (unexposed) group
- 132
- Group 1 sample size Number of subjects in the case (exposed) group
- 166
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex, proton-pump inhibitor, Confounders controlled for: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin, geographic area
Alpha Diversity
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental. TableS9
Description: Differential abundant taxa between metformin-naive T2D and metformin-treated T2D in the combined Danish-Indian group
Abundance in Group 1: decreased abundance in metformin-treated T2D patients
| NCBI | Quality Control | Links |
|---|---|---|
| Faecalibacterium |
Revision editor(s): Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental. TableS9
Description: Differential abundant taxa between metformin-naive T2D and metformin-treated T2D in the combined Danish-Indian group
Abundance in Group 1: increased abundance in metformin-treated T2D patients
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides sp. |
Revision editor(s): ChiomaBlessing, Folakunmi
Experiment 5
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Curated date: 2023/11/05
Curator: ChiomaBlessing
Revision editor(s): ChiomaBlessing, Folakunmi, Fiddyhamma
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Type II diabetes mellitus adult onset diabetes,Adult-Onset Diabetes,adult-onset diabetes,Adult-Onset Diabetes Mellitus,diabetes mellitis type 2,diabetes mellitis type II,DIABETES MELLITUS TYPE 02,diabetes mellitus type 2,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Noninsulin Dependent,diabetes mellitus, noninsulin-dependent,Diabetes Mellitus, Slow Onset,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,Diabetes Mellitus, Type 2,diabetes mellitus, type 2,diabetes mellitus, type 2, protection against,Diabetes Mellitus, Type II,Diabetes, Type 2,diabetes, type 2,insulin resistance, susceptibility to,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes Mellitus,maturity-onset diabetes,Maturity-Onset Diabetes Mellitus,MODY,NIDDM,Non-Insulin Dependent Diabetes,non-insulin dependent diabetes,Non-Insulin Dependent Diabetes Mellitus,non-insulin dependent diabetes mellitus,non-insulin-dependent diabetes mellitus,noninsulin dependent diabetes,noninsulin-dependent diabetes mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus,T2DM - Type 2 Diabetes mellitus,T2DM - type 2 diabetes mellitus,Type 2 Diabetes,type 2 diabetes,Type 2 Diabetes Mellitus,type 2 diabetes mellitus,Type 2 Diabetes Mellitus Non-Insulin Dependent,type 2 diabetes mellitus non-insulin dependent,Type II Diabetes,type II diabetes,type II diabetes mellitus,Type II diabetes mellitus
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Normoglycemic (NG) controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Type 2 diabetes (T2D) patients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Individuals diagnosed with T2D
- Group 0 sample size Number of subjects in the control (unexposed) group
- 275
- Group 1 sample size Number of subjects in the case (exposed) group
- 298
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- geographic area
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental. Table S3A
Description: Differential abundant taxa between type 2 diabetes (T2D) VS normoglycemic controls (NG) in the combined Danish-Indian group
Abundance in Group 1: decreased abundance in Type 2 diabetes (T2D) patients
Revision editor(s): ChiomaBlessing, Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S3A & B
Description: Differential abundant taxa between type 2 diabetes (T2D) VS normoglycemic controls (NG) in the combined Danish-Indian group
Abundance in Group 1: increased abundance in Type 2 diabetes (T2D) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Blautia sp. | ||
| Coprococcus sp. | ||
| Dorea | ||
| Firmicutes bacterium CAG:56 | ||
| Lachnoclostridium | ||
| Megasphaera | ||
| Oscillibacter |
Revision editor(s): ChiomaBlessing, Folakunmi
Experiment 6
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Curated date: 2023/11/05
Curator: ChiomaBlessing
Revision editor(s): ChiomaBlessing, Folakunmi, 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, proton-pump inhibitor, Confounders controlled for: "metformin" 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, Confounders controlled for: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin, geographic area
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental. Table S4A and B
Description: Differential abundant taxa between type 2 diabetes (T2D) VS normoglycemic controls (NG) in the combined Danish-Indian group
Abundance in Group 1: decreased abundance in Type 2 diabetes (T2D) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerosporobacter | ||
| Butyricicoccus | ||
| Subdoligranulum |
Revision editor(s): ChiomaBlessing, Folakunmi
Signature 2
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental. Table S4A and B
Description: Differential abundant taxa between type 2 diabetes (T2D) VS normoglycemic controls (NG) in the combined Danish-Indian group
Abundance in Group 1: increased abundance in Type 2 diabetes (T2D) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Firmicutes bacterium CAG:56 | ||
| Lachnoclostridium |
Revision editor(s): ChiomaBlessing, Folakunmi
Experiment 7
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Differences from previous experiment shown
Subjects
- Location of subjects
- Denmark
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 4 months
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, body mass index, sex, proton-pump inhibitor, Confounders controlled for: "metformin" 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, Confounders controlled for: "sulfonyl urea" 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.sulfonyl urea, Confounders controlled for: "statin" 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.statin
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Folakunmi on 2024-1-4
Source: Supplemental Table S6A
Description: Differentially abundant taxa between type 2 diabetes (T2D) VS normoglycemic controls (NG) in the Danish substudy
Abundance in Group 1: increased abundance in Type 2 diabetes (T2D) patients
| NCBI | Quality Control | Links |
|---|---|---|
| Lachnoclostridium |
Revision editor(s): ChiomaBlessing, Folakunmi
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