Bile’s Hidden Weapon: Modulating the Microbiome and Tumor Microenvironment

The human gut microbiome is a dynamic and intricate ecosystem, composed of trillions of microorganisms that play a pivotal role in maintaining overall health and well-being. However, the gut microbiome is constantly exposed to various environmental factors, including the bile produced by the liver, which can significantly impact its composition and function. Bile acids, secreted by the liver and stored in the gallbladder, modulate the gut microbiome, influencing its composition and function. This altered microbiome profile can, in turn, impact the tumor microenvironment (TME), promoting an immunosuppressive environment that favors tumor growth and metastasis. Furthermore, changes in the gut microbiome can also influence the production of bile acids and other metabolites that directly affect cancer cells and their behavior. Moreover, bile acids have been shown to shape the microbiome and increase antibiotic resistance, underscoring the need for targeted interventions. This review provides a comprehensive overview of the intricate relationships between bile, the gut microbiome, and the TME, highlighting the mechanisms by which this interplay drives cancer progression and resistance to therapy. Understanding these complex interactions is crucial for developing novel therapeutic strategies that target the gut-bile-TME axis and improve patient outcomes.