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Published on: September 22, 2019
Investigating the causal links among gut microbiome features, inflammation-related proteins, and diverticular
Jie Zhou1,2, Yixin Xu1,2, Haitao Wang3
1Department of Gastrointestinal Surgery, The Wujin Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu Province, China.
Abstract:
The pathophysiological mechanisms underlying diverticular disease (DD) remain incompletely understood, and there is considerable debate regarding the roles of gut microbiome features and inflammation-related proteins in the development of the disease. In this study, we employed mediation Mendelian randomization (MR) analysis to investigate the causal relationships among these 3 factors. In this study, we conducted a MR analysis on the genome-wide association studies data of 412 gut microbiome features (207 microbial taxa and 205 pathways), 91 inflammation-related proteins, and DD. We employed the inverse-variance weighted (IVW) method as our primary screening approach, followed by a mediation MR analysis to explore potential causal relationships among these 3 aspects. Our findings were further reinforced by comprehensive heterogeneity analyses, horizontal pleiotropy testing, outlier detection, and "leave-one-out" sensitivity analysis. Through our screening process, we identified potential causal relationships between DD and 18 gut microbiome features, as well as 6 inflammation-related proteins. These include s_Oscillibacter_unclassified (IVW odds ratio (OR): 1.139; 95% confidence interval (CI): 1.044-1.241, P = .003), g_Bilophila (IVW OR: 1.107, 95% CI: 1.016-1.206, P = .020), T-cell surface glycoprotein CD5 levels (IVW OR: 1.065, 95% CI: 1.011-1.123, P = .019), and inosine 5'-phosphate biosynthesis I (IVW OR: 0.882, 95% CI: 0.800-0.973, P = .012), etc. In the mediation MR analysis, we found that the genetic predictors of g_Bilophila and inosine 5'-phosphate biosynthesis I could explain 23.956% and 24.630% of the variation in T-cell surface glycoprotein CD5 levels, respectively. This study detailed analysis of the links between gut microbiome features, inflammation-related proteins, and DD offers key insights into DD pathogenesis and prevention.
Insights
This study used Mendelian randomization to uncover causal links between gut microbiome features, inflammation proteins, and diverticular disease (DD). Specific bacteria like g_Bilophila and proteins such as CD5 were identified as potential contributors to DD development.
Area of Science:
- Gastroenterology and Genetics
- Microbiome Research
- Immunology
Background:
- Diverticular disease (DD) pathogenesis is not fully understood, with ongoing debate on the roles of gut microbiota and inflammation.
- Existing research lacks comprehensive causal investigations into the interplay between microbiome, inflammation, and DD.
Purpose of the Study:
- To investigate the causal relationships between gut microbiome features, inflammation-related proteins, and diverticular disease (DD) using mediation Mendelian randomization (MR).
- To identify specific microbial taxa, pathways, and proteins causally associated with DD.
- To explore the mediating role of inflammation-related proteins in the gut microbiome-DD axis.
Main Methods:
- Genome-wide association studies (GWAS) data for 412 gut microbiome features and 91 inflammation-related proteins were analyzed.
- Mediation Mendelian randomization (MR) analysis, including inverse-variance weighted (IVW) method, was employed to assess causal links.
- Sensitivity analyses, including heterogeneity testing and pleiotropy assessment, were performed to ensure robustness.
Main Results:
- Potential causal relationships were identified between DD and 18 gut microbiome features and 6 inflammation-related proteins.
- Specific associations include s_Oscillibacter_unclassified (OR: 1.139), g_Bilophila (OR: 1.107), and T-cell surface glycoprotein CD5 levels (OR: 1.065).
- Mediation analysis revealed that genetic predictors of g_Bilophila and inosine 5 extprime-phosphate biosynthesis I explained significant variation in T-cell surface glycoprotein CD5 levels (23.956% and 24.630%, respectively).
Conclusions:
- This study provides novel insights into the complex interplay between the gut microbiome, inflammation, and diverticular disease.
- Identified microbial and protein factors offer potential targets for understanding and preventing DD.
- The findings highlight the utility of mediation MR in dissecting disease etiology.
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