The role of the gut microbiome in the development of hepatobiliary cancers

Abstract

Hepatobiliary cancers, including hepatocellular carcinoma and cancers of the biliary tract, share high mortality and rising incidence rates. They may also share several risk factors related to unhealthy western-type dietary and lifestyle patterns as well as increasing body weights and rates of obesity. Recent data also suggest a role for the gut microbiome in the development of hepatobiliary cancer and other liver pathologies. The gut microbiome and the liver interact bidirectionally through the “gut-liver axis,” which describes the interactive relationship between the gut, its microbiota, and the liver. Here, we review the gut-liver interactions within the context of hepatobiliary carcinogenesis by outlining the experimental and observational evidence for the roles of gut microbiome dysbiosis, reduced gut barrier function, and exposure to inflammatory compounds as well as metabolic dysfunction as contributors to hepatobiliary cancer development. We also outline the latest findings regarding the impact of dietary and lifestyle factors on liver pathologies as mediated by the gut microbiome. Finally, we highlight some emerging gut microbiome editing techniques currently being investigated in the context of hepatobiliary diseases. Although much work remains to be done in determining the relationships between the gut microbiome and hepatobiliary cancers, emerging mechanistic insights are informing treatments, such as potential microbiota manipulation strategies and guiding public health advice on dietary/lifestyle patterns for the prevention of these lethal tumors.

The causal relationship between gut microbiota and biliary tract cancer: comprehensive bidirectional Mendelian randomization analysis

“…Chronic inflammation can lead to DNA damage, promoting mutations and the initiation of cancerous growths. Furthermore, certain Streptococcus species produce metabolites that may have carcinogenic properties, potentially impacting the development of BTC (Plieskatt et al, 2013;Daniel et al, 2023). Members of the Veillonellaceae family are known for their role in the fermentation of proteins and carbohydrates in the gut.…”

Integrated Metabolomic and Transcriptomic Analysis Reveals Potential Gut-Liver Crosstalks in the Lipogenesis of Chicken

“…Through the portal vein, the microbiota in the gut can deliver metabolites to the liver that affect liver function by influencing hepatic gene expression [13,18]. Therefore, we identified DEGs between liver samples of chicken in the NFD and HFD groups and analyzed their correlations with the ten important metabolites.…”

Metabolic reprogramming in the tumor microenvironment of liver cancer

“…This gut-liver axis executes critical functions in nutrient metabolism and bacterial metabolite clearance, mainly through the portal vein [192]. Emerging studies have addressed the pivotal roles of the gut microbiota in PLC pathogenesis and anti-tumor therapy [5,[193][194][195][196]. The gut microbiota is closely associated with immunity and metabolism, underscoring their vital role in health and disease.…”