Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis
Abstract Purpose To investigate the causal relationships between gut microbiota and novel adult-onset type 2 diabetes mellitus(T2DM) subtypes. Methods We conducted Mendelian randomization (MR) analyses using genome-wide association data from European populations. Initial MR analyses examined associa...
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BMC
2025-03-01
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| Series: | BMC Endocrine Disorders |
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| Online Access: | https://doi.org/10.1186/s12902-025-01863-x |
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| author | Zhichao Ruan Jiangteng Liu Jinxi Zhao |
| author_facet | Zhichao Ruan Jiangteng Liu Jinxi Zhao |
| author_sort | Zhichao Ruan |
| collection | DOAJ |
| description | Abstract Purpose To investigate the causal relationships between gut microbiota and novel adult-onset type 2 diabetes mellitus(T2DM) subtypes. Methods We conducted Mendelian randomization (MR) analyses using genome-wide association data from European populations. Initial MR analyses examined associations between gut microbiota and four T2DM subtypes, followed by validation analyses using type 1 diabetes mellitus(T1DM) and T2DM GWAS data. We also performed bidirectional MR analyses and tested for heterogeneity and pleiotropy across all analyses. Results Our MR analyses revealed distinctive associations between gut microbiota and T2DM subtypes: six bacterial taxa with severe insulin-deficient diabetes (SIDD), four with severe insulin-resistant diabetes (SIRD), eight with mild obesity-related diabetes (MOD), and eight with mild age-related diabetes (MARD). These associations were distinct from T1DM findings. Six bacterial taxa were validated in T2DM analyses, with four showing directionally consistent effects: Class Clostridia (OR = 0.57, P = 0.045) and Order Clostridiales (OR = 0.57, P = 0.045) were associated with reduced MOD risk, while species Catus (OR = 1.80, P = 0.007) was associated with increased MOD risk, and genus Holdemania (OR = 2.51, P = 0.004) was associated with increased SIRD risk. No significant heterogeneity or pleiotropy was observed across analyses. Conclusions Our MR analyses reveal novel causal relationships between gut microbiota and adult-onset T2DM subtypes, though further validation studies are warranted. |
| format | Article |
| id | doaj-art-d2d2fd16a0ea45ce9ef484cec89c91f7 |
| institution | Kabale University |
| issn | 1472-6823 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj-art-d2d2fd16a0ea45ce9ef484cec89c91f72025-08-20T03:40:50ZengBMCBMC Endocrine Disorders1472-68232025-03-0125111010.1186/s12902-025-01863-xCausal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysisZhichao Ruan0Jiangteng Liu1Jinxi Zhao2Department of Endocrinology, Dongzhimen Hospital, Beijing University of Chinese MedicineDepartment of Endocrinology, Dongzhimen Hospital, Beijing University of Chinese MedicineDepartment of Endocrinology, Dongzhimen Hospital, Beijing University of Chinese MedicineAbstract Purpose To investigate the causal relationships between gut microbiota and novel adult-onset type 2 diabetes mellitus(T2DM) subtypes. Methods We conducted Mendelian randomization (MR) analyses using genome-wide association data from European populations. Initial MR analyses examined associations between gut microbiota and four T2DM subtypes, followed by validation analyses using type 1 diabetes mellitus(T1DM) and T2DM GWAS data. We also performed bidirectional MR analyses and tested for heterogeneity and pleiotropy across all analyses. Results Our MR analyses revealed distinctive associations between gut microbiota and T2DM subtypes: six bacterial taxa with severe insulin-deficient diabetes (SIDD), four with severe insulin-resistant diabetes (SIRD), eight with mild obesity-related diabetes (MOD), and eight with mild age-related diabetes (MARD). These associations were distinct from T1DM findings. Six bacterial taxa were validated in T2DM analyses, with four showing directionally consistent effects: Class Clostridia (OR = 0.57, P = 0.045) and Order Clostridiales (OR = 0.57, P = 0.045) were associated with reduced MOD risk, while species Catus (OR = 1.80, P = 0.007) was associated with increased MOD risk, and genus Holdemania (OR = 2.51, P = 0.004) was associated with increased SIRD risk. No significant heterogeneity or pleiotropy was observed across analyses. Conclusions Our MR analyses reveal novel causal relationships between gut microbiota and adult-onset T2DM subtypes, though further validation studies are warranted.https://doi.org/10.1186/s12902-025-01863-xGut microbiotaType 2 diabetes mellitusMendelian randomizationGenetic variants |
| spellingShingle | Zhichao Ruan Jiangteng Liu Jinxi Zhao Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis BMC Endocrine Disorders Gut microbiota Type 2 diabetes mellitus Mendelian randomization Genetic variants |
| title | Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis |
| title_full | Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis |
| title_fullStr | Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis |
| title_full_unstemmed | Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis |
| title_short | Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis |
| title_sort | causal associations between gut microbiota and type 2 diabetes mellitus subtypes a mendelian randomization analysis |
| topic | Gut microbiota Type 2 diabetes mellitus Mendelian randomization Genetic variants |
| url | https://doi.org/10.1186/s12902-025-01863-x |
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