Large-scale causal analysis of gut microbiota and six common complications of diabetes: a mendelian randomization study
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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
Wang J, Teng M, Feng R, Su X, Xu K, Wang J, Wang G, Zhang Y, Xu P
Journal
Diabetology & metabolic syndrome
Year
2024
Keywords:
Complications of diabetes, Genome-wise association studies, Gut microbiota, Mendelian randomization study, Single-nucleotide polymorphism
BACKGROUND: This study aimed to reveal the association between the gut microbiota (GM) and six diabetic complications: diabetic hypoglycemia; ketoacidosis; nephropathy; neuropathy; retinopathy; and Charcot's foot. METHODS: GM data were obtained from the MiBioGen consortium and Dutch Microbiome Project while data on the six diabetic complications were obtained from the FinnGen consortium. Two-sample Mendelian randomization (TSMR) was performed to explore the association between GM and the common diabetic complications. Inverse MR analysis was conducted to examine the effect of diabetic complications on the identified GM. Sensitivity tests were conducted to validate the stability of the results. Finally, multivariate MR (MVMR) was performed to determine whether GM had a direct influence on the diabetic complications. RESULTS: After multiple corrections, the inverse variance weighted (IVW) results predicted 61 suggestive markers between GM and six diabetic complications. In particular, the IVW results revealed that the Bacteroidia class and Bacteroidales order were positively associated with diabetic hypoglycemia while the Verrucomicrobiae class and Verrucomicrobiales order were positively associated with diabetic nephropathy. Based on the replication analysis, these results were identified to be stable. MVMR showed that the results remained stable after accounting for traditional risk factors. CONCLUSION: Extensive causal associations were found between GM and diabetic complications, which may provide new insights into the mechanisms of microbiome-mediated complications of diabetes.
Experiment 1
Needs review
Subjects
- Location of subjects
- Finland
- 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
- Hypoglycemia Hypoglycaemia,Low blood sugar,Hypoglycemia,hypoglycemia
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Controls
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic hypoglycemia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic hypoglycemia obtained from the FinnGen consortium.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 271817
- Group 1 sample size Number of subjects in the case (exposed) group
- 7332
Lab analysis
- 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
Statistical Analysis
- 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, sex
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Diabetic hypoglycemia
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidia | ||
| Catenibacterium | ||
| Eggerthella | ||
| Ruminococcaceae UCG 009Ruminococcaceae UCG 009 | ||
| Bacteroidales | ||
| Verrucomicrobiales |
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Diabetic hypoglycemia
| NCBI | Quality Control | Links |
|---|---|---|
| Alcaligenaceae | ||
| Defluviitaleaceae UCG 011Defluviitaleaceae UCG 011 | ||
| DefluviitaleaceaDefluviitaleacea | ||
| Faecalibacterium | ||
| Phascolarctobacterium |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 2
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic ketoacidosis DIABETES MELLITUS, KETOSIS-PRONE,diabetes mellitus, ketosis-prone,Diabetic Ketoacidosis,diabetic ketoacidosis,ketosis-prone diabetes mellitus,KPD,Diabetic ketoacidosis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic ketoacidosis
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic ketoacidosis obtained from the FinnGen consortium.
- Group 1 sample size Number of subjects in the case (exposed) group
- 7841
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Diabetic ketoacidosis
| NCBI | Quality Control | Links |
|---|---|---|
| Adlercreutzia | ||
| Allisonella | ||
| Alistipes | ||
| Lachnospiraceae UCG 001Lachnospiraceae UCG 001 | ||
| Olsenella |
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Diabetic ketoacidosis
| NCBI | Quality Control | Links |
|---|---|---|
| Eubacterium coprostanoligenes | ||
| Ruminococcaceae bacterium UCG-005 | ||
| Desulfovibrionales |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 3
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic nephropathy Diabetes with renal manifestations,Diabetes with renal manifestations (disorder),Diabetes-nephrosis syndrome,Diabetes-nephrosis syndrome (disorder),Diabetic Glomerulosclerosis,Diabetic Kidney Disease,diabetic kidney disease,Diabetic Kidney Diseases,Diabetic Nephropathies,diabetic nephropathy,Diabetic renal disease,Diabetic renal disease (disorder),DKD,DMII RENAL UNCNTRLD,DMII RENL NT ST UNCNTRLD,Glomerulosclerosis, Diabetic,Glomerulosclerosis, Nodular,Intracapillary Glomerulosclerosis,Kidney Disease, Diabetic,Kidney Diseases, Diabetic,Kimmelstiel - Wilson disease,Kimmelstiel Wilson Disease,Kimmelstiel Wilson Syndrome,Kimmelstiel-Wilson Disease,Kimmelstiel-Wilson Syndrome,Nephropathies, Diabetic,Nephropathy, Diabetic,Nephrotic syndrome due to diabetes mellitus,Nephrotic syndrome in diabetes mellitus,Nephrotic syndrome in diabetes mellitus (disorder),Nodular Glomerulosclerosis,Renal disorder associated with diabetes mellitus,Syndrome, Kimmelstiel-Wilson,type 1 diabetes nephropathy,type 2 diabetes nephropathy,Diabetic nephropathy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic Nephropathy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic nephropathy obtained from the FinnGen consortium.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 308539
- Group 1 sample size Number of subjects in the case (exposed) group
- 4111
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Diabetic Nephropathy
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidia | ||
| Verrucomicrobiaceae | ||
| Verrucomicrobiia | ||
| Akkermansia | ||
| Catenibacterium | ||
| Lachnoclostridium | ||
| Parasutterella | ||
| Bacteroidales | ||
| Bacteroidota | ||
| Verrucomicrobiales |
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Diabetic Nephropathy
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidaceae | ||
| Victivallaceae | ||
| Bacteroides | ||
| Coprococcus | ||
| Lactococcus |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 4
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic retinopathy Diabetic Retinopathies,diabetic retinopathy,retinal abnormality - diabetes-related,Retinopathies, Diabetic,Retinopathy, Diabetic,Diabetic retinopathy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic Retinopathy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic retinopathy obtained from the FinnGen consortium.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 344569
- Group 1 sample size Number of subjects in the case (exposed) group
- 6818
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Diabetic Retinopathy
| NCBI | Quality Control | Links |
|---|---|---|
| Alistipes | ||
| Christensenellaceae R7 groupChristensenellaceae R7 group | ||
| Eggerthella | ||
| Ruminococcaceae UCG 013Ruminococcaceae UCG 013 | ||
| Bacillota |
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Diabetic Retinopathy
| NCBI | Quality Control | Links |
|---|---|---|
| Acidaminococcaceae | ||
| Peptococcaceae | ||
| Eubacterium coprostanoligenes |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 5
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic neuropathy Amyotrophies, Diabetic,Amyotrophy, Diabetic,Asymmetric Polyneuropathy, Diabetic,Diabetic Amyotrophies,Diabetic Amyotrophy,Diabetic Asymmetric Polyneuropathies,Diabetic Asymmetric Polyneuropathy,Diabetic Autonomic Neuropathies,Diabetic Autonomic Neuropathy,Diabetic Mononeuropathies,Diabetic Mononeuropathy,Diabetic Mononeuropathy Simplex,Diabetic Mononeuropathy Simplices,diabetic neuropathies,diabetic neuropathy,Painful Diabetic Neuropathies,Painful Diabetic Neuropathy,Diabetic neuropathy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic Neuropathy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic neuropathy obtained from the FinnGen consortium.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 271817
- Group 1 sample size Number of subjects in the case (exposed) group
- 2843
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Diabetic Neuropathy
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Diabetic Neuropathy
| NCBI | Quality Control | Links |
|---|---|---|
| Eisenbergiella |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 6
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic foot Diabetic Feet,Diabetic Foot Ulcer,Diabetic foot,diabetic foot
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Charcot foot
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with Charcot foot obtained from the FinnGen consortium.
- Group 1 sample size Number of subjects in the case (exposed) group
- 473
Lab analysis
Statistical Analysis
Signature 1
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: increased abundance in Charcot foot
| NCBI | Quality Control | Links |
|---|---|---|
| Anaerostipes | ||
| Collinsella | ||
| Agathobacter rectalis | ||
| Hungatella | ||
| Bacillota |
Revision editor(s): Aleru Divine, WikiWorks
Signature 2
Needs review
Source: Figure 4
Description: Significant results between the gut microbiota and the six common complications of diabetes.
Abundance in Group 1: decreased abundance in Charcot foot
| NCBI | Quality Control | Links |
|---|---|---|
| Erysipelotrichaceae | ||
| Erysipelotrichia | ||
| Peptococcaceae | ||
| Phascolarctobacterium | ||
| Erysipelotrichales |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 7
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Hypoglycemia Hypoglycaemia,Low blood sugar,Hypoglycemia,hypoglycemia
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic hypoglycemia
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic hypoglycemia obtained from the FinnGen consortium.
- Group 0 sample size Number of subjects in the control (unexposed) group
- Not specified
- Group 1 sample size Number of subjects in the case (exposed) group
- Not specified
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, alcohol drinking, smoking behavior, sex, Confounders controlled for: "triglycerides levels" 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.triglycerides levels, Confounders controlled for: "low-density lipoprotein levels" 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.low-density lipoprotein levels
Signature 1
Needs review
Source: Figure 5
Description: Multivariate Mendelian Randomization (MR) results: After adjusting for confounding factors, including consumption of alcoholic drinks, LDL levels, TG levels, and smoking.
Abundance in Group 1: increased abundance in Diabetic hypoglycemia
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidia |
Revision editor(s): Aleru Divine, WikiWorks
Experiment 8
Needs review
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Diabetic nephropathy Diabetes with renal manifestations,Diabetes with renal manifestations (disorder),Diabetes-nephrosis syndrome,Diabetes-nephrosis syndrome (disorder),Diabetic Glomerulosclerosis,Diabetic Kidney Disease,diabetic kidney disease,Diabetic Kidney Diseases,Diabetic Nephropathies,diabetic nephropathy,Diabetic renal disease,Diabetic renal disease (disorder),DKD,DMII RENAL UNCNTRLD,DMII RENL NT ST UNCNTRLD,Glomerulosclerosis, Diabetic,Glomerulosclerosis, Nodular,Intracapillary Glomerulosclerosis,Kidney Disease, Diabetic,Kidney Diseases, Diabetic,Kimmelstiel - Wilson disease,Kimmelstiel Wilson Disease,Kimmelstiel Wilson Syndrome,Kimmelstiel-Wilson Disease,Kimmelstiel-Wilson Syndrome,Nephropathies, Diabetic,Nephropathy, Diabetic,Nephrotic syndrome due to diabetes mellitus,Nephrotic syndrome in diabetes mellitus,Nephrotic syndrome in diabetes mellitus (disorder),Nodular Glomerulosclerosis,Renal disorder associated with diabetes mellitus,Syndrome, Kimmelstiel-Wilson,type 1 diabetes nephropathy,type 2 diabetes nephropathy,Diabetic nephropathy
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Diabetic Nephropathy
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with diabetic nephropathy obtained from the FinnGen consortium.
Lab analysis
Statistical Analysis
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, alcohol drinking, smoking behavior, sex, Confounders controlled for: "low-density lipoprotein levels" 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.low-density lipoprotein levels, Confounders controlled for: "triglycerides levels" 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.triglycerides levels
Signature 1
Needs review
Source: Figure 5
Description: Multivariate Mendelian Randomization (MR) results: After adjusting for confounding factors, including consumption of alcoholic drinks, LDL levels, TG levels, and smoking.
Abundance in Group 1: increased abundance in Diabetic Nephropathy
| NCBI | Quality Control | Links |
|---|---|---|
| Verrucomicrobiia |
Revision editor(s): Aleru Divine, WikiWorks
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