Involvement of the gut microbiota in cancer cachexia.

ABSTRACT

Cancer cachexia, or the unintentional loss of body weight in cancer patients, is a multi-organ and multi-factorial syndrome with a complex and largely unknown etiology; however, metabolic dysfunction and inflammation remain hallmarks of cancer-associated wasting. While cachexia manifests with muscle and adipose tissue loss, perturbations to the gastrointestinal tract may serve as the front line for both impaired nutrient absorption and immune activating gut dysbiosis. Investigations into the gut microbiota have exploded within the past 2 decades, demonstrating multiple gut-tissue axes; however, the link between adipose and skeletal muscle wasting and the gut microbiota with cancer is only beginning to be understood. Further, the most used anti-cancer drugs (e.g. chemotherapy, immune checkpoint inhibitors) negatively impact gut homeostasis, potentially exacerbating wasting and contributing to poor patient outcomes and survival. In this current review, we 1) highlight our current understanding of the microbial changes that occur with cachexia, 2) discuss how microbial changes may contribute to adipose and skeletal muscle wasting, and 3) outline study design considerations needed when examining the role of the microbiota in cancer-induced cachexia.