Elucidating the causal association between gut microbiota and intrahepatic cholangiocarcinoma through Mendelian randomization analysis

Abstract

BackgroundIntrahepatic cholangiocarcinoma (ICC) is an aggressive liver cancer with poor prognosis. The gut microbiota has been linked to ICC, but evidence for causality is lacking. Elucidating causal gut microbiota-ICC links could inform prevention and treatment strategies.Materials and methodsWe performed a bidirectional two-sample Mendelian randomization (MR) study to investigate causal associations between gut microbiota and ICC risk. Genome-wide significant single nucleotide polymorphisms (SNPs) associated with gut microbiota abundances were utilized as instrumental variables (IVs). Multiple methods assessed causality and sensitivity analyses evaluated result robustness. Bioinformatics analysis of genetic loci linked to gut microbiota and ICC examined potential mechanisms.ResultsGenetically predicted increases in Veillonellaceae, Alistipes, Enterobacteriales, and Firmicutes were suggestively associated with higher ICC risk, while increases in Anaerostipes, Paraprevotella, Parasutterella, and Verrucomicrobia appeared protective. Bioinformatics analysis revealed differentially expressed genes near gut microbiota-associated loci may influence ICC through regulating pathways and tumor immune microenvironment.ConclusionOur findings provide suggestive evidence for causal links between specific gut microbiota and ICC risk.

IL-17A inhibitors alleviate Psoriasis with concomitant restoration of intestinal/skin microbiota homeostasis and altered microbiota function

“…Previous studies have shown that a high-fat diet (HFD) and Clostridium difficile infection (CDI) can decrease the abundance of Parasutterella in the gut ( 90 , 91 ). However, an increase in Parasutterella has been found to have a protective effect against Intrahepatic Cholangiocarcinoma (ICC) ( 92 ). Parasutterella produces succinic acid and hypoxanthine ( 93 ), and is negatively correlated with levels of faecal Deoxycholic Acid (DCA) and Lithocholic Acid (LCA) ( 94 ).…”

Causal associations of gut microbiota and pulmonary tuberculosis: a two-sample Mendelian randomization study

“…Our study identified a causal association between three gut microbiota, namely Parasutterella, Dorea, and Lachnoclostridium, and PTB. Notably, Parasutterella has been found to have a causal relationship with various other conditions in several Mendelian randomization studies, including COVID-19 ( Chen H. et al, 2023 ), intrahepatic cholangiocarcinoma (ICC) ( Chen Z. et al, 2023 ), chronic kidney disease (CKD) ( Ren et al, 2023 ), and prostatitis ( Shen et al, 2024 ). Meanwhile, Dorea is associated with autism spectrum disorder (ASD) ( Li Z. et al, 2023 ), inflammatory bowel disease (IBD) ( Zhang et al, 2021 ), hypertensive disorders in pregnancy (HDP) ( Wu et al, 2023a ), polycystic ovary syndrome (PCOS) ( Min et al, 2023 ), hemorrhagic stroke ( Shen et al, 2023 ), age-related macular degeneration (AMD) ( Li and Lu, 2023 ), nicotine dependence ( Chen Y. et al, 2023 ), and insomnia ( Li Z. et al, 2023 ).…”

Identifying Proteins and Amino Acids Associated with Liver Cancer Risk: A Study Utilizing Mendelian Randomization and Bulk RNA Sequencing Analysis

“…Independent sample MR, two-sample MR, multivariate MR, and bidirectional MR extensively investigate the causal association between risk factors and diseases [ 15 , 16 , 17 ]. The MR method has proven the causal association between unhealthy lifestyle choices (such as alcohol use, smoking, and obesity) and HCC [ 18 , 19 ]. Drug MR methods have garnered considerable interest for their use in drug development and predicting medication effects.…”