The Microbiota and Cancer Cachexia

Abstract

Cancer cachexia is a multifactorial syndrome defined by weight loss, muscle wasting, and systemic inflammation. It affects the majority of patients with advanced cancer and is associated with poor treatment response, early mortality and decreased quality of life. The microbiota has been implicated in cancer cachexia through pathways of systemic inflammation, gut barrier dysfunction and muscle wasting. The imbalance of the microbiota, known as dysbiosis, has been shown to influence cancer cachexia. Bacteria that play beneficial and detrimental roles in the disease pathogenesis have been identified. The phenotype of cancer cachexia is associated with decreased levels of Lactobacillales and increased levels of Enterobacteriaceae and Parabacteroides. Currently, there are no treatment options that demonstrate increased survival or the quality of life in patients suffering from cancer cachexia. Through the manipulation of beneficial bacteria in the gut microbiota, different treatment options have been explored. Prebiotics and probiotics have been shown to improve outcomes in animal models of cachexia. Expounding on this mechanism, fecal microbiota transplant (FMT) holds promise for a future treatment of cancer cachexia. Further research is necessary to address this detrimental disease process and improve the lives of patients suffering from cancer cachexia.

Keywords: cancer cachexia; dysbiosis; fecal microbiota transplantation; gut barrier dysfunction; microbiota; muscle wasting; prebiotics; probiotics; systemic inflammation.

Figure 1

Cycle of systemic inflammation and the influence of cancer progression, dysbiosis, gut barrier dysfunction and muscle wasting in cancer cachexia. This diagram illustrates the interplay of systemic inflammation, likely from disease progression, which leads to dysbiosis and gut barrier dysfunction. Gut barrier dysfunction leads to increasing permeability of pathologic bacteria and endotoxemia, and perpetuates systemic inflammation and muscle wasting.