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. 2025 Mar 24;25(1):79.
doi: 10.1186/s12902-025-01863-x.

Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis

Zhichao Ruan  1 , Jiangteng Liu  1 , Jinxi Zhao  2
Affiliations

Causal associations between gut microbiota and type 2 diabetes mellitus subtypes: a mendelian randomization analysis

Zhichao Ruan et al. BMC Endocr Disord. .

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.

Keywords: Genetic variants; Gut microbiota; Mendelian randomization; Type 2 diabetes mellitus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Diagram for key assumptions of mendelian randomization analyses
Fig. 2
Fig. 2
Forest plot of mendelian randomization analysis of gut microbiota and T2DM subtypes
Fig. 3
Fig. 3
Taxonomic network visualization of gut microbiota associated with T2DM subtypes identified through mendelian randomization
Fig. 4
Fig. 4
UpSet plot of gut microbiota associations across six diabetes phenotypes
Fig. 5
Fig. 5
Forest plot of shared gut microbial taxa between type 2 diabetes mellitus and its subtypes
See this image and copyright information in PMC

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References

    1. Ong KL, Stafford LK, McLaughlin SA, Boyko EJ, Vollset SE, Smith AE, et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the global burden of Disease Study 2021. Lancet. 2023;402:203–34. - PMC - PubMed
    1. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of Medical Care in Diabetes—2021. Diabetes Care. 2020;44 Supplement1:S15–33. - PubMed
    1. Mahajan A, Wessel J, Willems SM, Zhao W, Robertson NR, Chu AY, et al. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes. Nat Genet. 2018;50:559–71. - PMC - PubMed
    1. Franks PW, McCarthy MI. Exposing the exposures responsible for type 2 diabetes and obesity. Science. 2016;354:69–73. - PubMed
    1. Ahlqvist E, Prasad RB, Groop L. 100 YEARS OF INSULIN: towards improved precision and a new classification of diabetes mellitus. J Endocrinol. 2022;252:R59–70. - PubMed

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