Front Genet. 2024 Nov 11;15:1362139. doi: 10.3389/fgene.2024.1362139. eCollection 2024.
ABSTRACT
BACKGROUND: Liver disease is among the top ten causes of death globally. With studies suggesting a link between gut microbiota (GM) and liver disease.
METHOD: We selected summary statistics data from the largest available whole-genome association study (n = 13,266) of GM by the MiBioGen consortium as the exposure, and obtained liver disease-related data from IEU Open GWAS and The NHGRI-EBI GWAS Catalog. A two-sample Mendelian Randomization (MR) analysis employing various methods, to establish the causal relationship between GM and five liver diseases. Meanwhile, single-cell RNA sequencing data were used to examine Prevotella-related genes expression under healthy and disease liver.
RESULTS: The IVW analysis indicate a causal relationship between GM and liver diseases, with Prevotella exhibiting a protective effect in all five liver diseases: Alcoholic liver disease (OR:0.81,95% confidence interval:0.66-1.00,P IVW = 0.0494); Cirrhosis (OR: 0.85,95% confidence interval: 0.73-0.99,P IVW = 0.0397); Hepatic failure, not elsewhere classified (OR:0.60,95% confidence interval:0.37-0.95,P IVW = 0.0305); Benign neoplasm:Liver (OR:0.39,95% confidence interval:0.2-0.75,P IVW = 0.0046); Malignant neoplasm of liver, primary (OR:0.41, 95% confidence interval:0.18-0.93,P IVW = 0.0334). The single-cell results suggest differential expression of Prevotella-related genes between liver disease patients and healthy individuals.
CONCLUSION: Our MR results show a causal relationship between the GM and liver disease. Prevotella displays a notable protective effect. This finding may enhance the precision of GM-based therapies and offer new insights for clinical research.
PMID:39588518 | PMC:PMC11586359 | DOI:10.3389/fgene.2024.1362139
