Background Previous studies have suggested a potential link between the gut microbiota and diverticulitis. However, the causal relationships as well as underlying mechanisms remain unclear.
Methods The causal effects of gut microbiota on diverticulosis & diverticulitis was assessed using two-sample Mendelian randomization analysis. The sensitivity analyses were also performed. We then used integrative bioinformatics tools to identify core genes associated with diverticulitis and explore their potential mechanisms and therapeutic targets.
Results Inverse variance weighted analysis indicated that Family XIII (OR=0.281, 95 % CI: 0.093-0.853, P = 0.025) and Defluviitaleaceae UCG-011 (OR=0.382, 95 % CI: 0.162-0.898, P = 0.027) were negatively associated with the risk of diverticulosis and diverticulitis, whereas Oscillospira (OR=3.514, 95 % CI: 1.146-10.779, P = 0.028), Ruminiclostridium 6 (OR=2.629, 95 % CI: 1.093-6.322, P = 0.031), Lachnoclostridium (OR=2.458, 95 % CI: 1.014-5.962, P = 0.047), and Desulfovibrionales (OR=2.157, 95 % CI: 1.038-4.480, P = 0.039) were positively associated with disease risk. The sensitivity analyses validated these correlations. Through SNP annotation, we identified 23 host genes associated with pathogenic gut microflora in diverticulosis and diverticulitis, and retrieved 213 diverticulitis-related genes from GeneCards. Intersection analysis revealed LRRC4C as the sole shared gene. Differential expression analysis further showed that LRRC4C was significantly downregulated in diverticulitis compared to infective colitis. Finally, eight candidate drugs were identified as potential inducers of LRRC4C expression.
Conclusion The research revealed potential causal relationships between gut microbiota and diverticulitis. LRRC4C was identified as a core gene associated with pathogenic microbial traits in diverticulitis, and candidate therapeutic drugs for diverticulitis based on LRRC4C were predicted, offering novel strategies for the prevention and management of the disease.
Ethics approval and consent to participate
This research utilized published studies and consortia that offer publicly available summary statistics. All original studies underwent approval by the respective ethical review board, and participants provided informed consent. Furthermore, no individual-level data was utilized in this study, hence no additional ethical review board approval was necessary.
Author contributions
Conceptualization: Wende Hao.Data curation: Wende Hao.Formal analysis: Wende Hao.Investigation: Wende Hao.Software: Wende Hao.Methodology: Wende Hao.Supervision: Zhenjun Wang.Funding acquisition: Huachong Ma.Writing-original draft: Wende Hao.Writing-review & editing: Huachong Ma.
Consent for publication
Not applicable.
Funding
This work was supported by the Wu Jieping Medical Foundation Special Fund for Clinical Research (Grant No. 320.6750.2022-07-15).
Data availability
The analyzed datasets generated during the study are available from the corresponding author upon reasonable request.
Declaration of Competing Interest
The authors declare no competing interests.
Acknowledgements
We gratefully acknowledge the participants and investigators of the UK Biobank study and the MiBioGen consortium. We also thank the Gene Expression Omnibus (GEO) Database for generously sharing a large amount of data.
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