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Applying Advanced In Vitro Culturing Technology to Study the Human Gut Microbiota
Published on: February 15, 2019
Novel Insights into Immune Cell Function in Type 2 Diabetes Mediated by Gut Microbiota: A Two-Sample Mendelian
Zeyu Zhou1,2, Zenghui Liu3, Siming Wang1,2
1Department of Clinical Laboratory, Affiliated Hospital of Chengde Medical College, Chengde, Hebei Province, China.
Introduction:
The role of immune cells in type 2 diabetes mellitus (T2DM) development is well-studied, but their interactions with the gut microbiota and the mediating role in this process remain unclear.
Methods:
We analyzed 731 immune cell phenotypes (3,757 Europeans), 473 gut microbiota traits (5,959 Finns), and T2DM data (over 400,000 Finns). Mendelian randomization (MR) was based on three assumptions: the instrumental variable (IV) is associated with exposure, IV is not influenced by confounding, and IV affects the outcome only through exposure. We selected single-nucleotide polymorphisms (SNPs) from genome-wide association studies as instrumental variables (IVs) to infer causal effects in two-sample MR analysis.
Results:
We identified 36 immune cell phenotypes associated with T2DM, including 29 protective factors and seven risk factors, as well as 10 gut microbiota significantly linked to T2DM, with eight protective factors and two risk factors. MR revealed that five gut microbiota mediated the relationship between immune cells and T2DM. For example, the effects of CD3 on resting Treg (OR: 1.0136), CD3 on CM CD4+ (OR: 1.0180), and CD3 on naive CD4+ cells (OR: 1.0150) in T2DM were found to be partially mediated by the species Bacillus. AYThe corresponding mediation effect proportions were 8.99%, 11.8%, and 11.4%.
Discussion:
MR analysis identified multiple gut microbiota mediators in the relationship between immune cells and T2DM, addressing previous observational evidence. Limitations included the European ancestry bias, among others.
Conclusion:
This study has highlighted the gut microbiota as a mediator between immune cells and T2DM, offering new insights for its early prevention and intervention.
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