The Role of Microbiota in Gastrointestinal Cancer and Cancer Treatment: Chance or Curse?

The gastrointestinal (GI) tract is home to a complex and dynamic community of microorganisms, comprising bacteria, archaea, viruses, yeast, and fungi. It is widely accepted that human health is shaped by these microbes and their collective microbial genome. This so-called second genome plays an important role in normal functioning of the host, contributing to processes involved in metabolism and immune modulation. Furthermore, the gut microbiota also is capable of generating energy and nutrients (eg, short-chain fatty acids and vitamins) that are otherwise inaccessible to the host and are essential for mucosal barrier homeostasis. In recent years, numerous studies have pointed toward microbial dysbiosis as a key driver in many GI conditions, including cancers. However, comprehensive mechanistic insights on how collectively gut microbes influence carcinogenesis remain limited. In addition to their role in carcinogenesis, the gut microbiota now has been shown to play a key role in influencing clinical outcomes to cancer immunotherapy, making them valuable targets in the treatment of cancer. It also is becoming apparent that, besides the gut microbiota’s impact on therapeutic outcomes, cancer treatment may in turn influence GI microbiota composition. This review provides a comprehensive overview of microbial dysbiosis in GI cancers, specifically esophageal, gastric, and colorectal cancers, potential mechanisms of microbiota in carcinogenesis, and their implications in diagnostics and cancer treatment.