Targeting Gut Microbiota in Cancer Cachexia: Towards New Treatment Options

Abstract

Cancer cachexia is a complex multifactorial syndrome whose hallmarks are weight loss due to the wasting of muscle tissue with or without the loss of adipose tissue, anorexia, systemic inflammation, and multi-organ metabolic alterations, which negatively impact patients' response to anticancer treatments, quality of life, and overall survival. Despite its clinical relevance, cancer cachexia often remains an underestimated complication due to the lack of rigorous diagnostic and therapeutic pathways. A number of studies have shown alterations in gut microbiota diversity and composition in association with cancer cachexia markers and symptoms, thus supporting a central role for dysbiosis in the pathogenesis of this syndrome. Different tools of microbiota manipulation, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been investigated, demonstrating encouraging improvements in cachexia outcomes. Albeit pioneering, these studies pave the way for future research with the aim of exploring the role of gut microbiota in cancer cachexia more deeply and setting up effective microbiota-targeting interventions to be translated into clinical practice.

Keywords: cancer cachexia; gut microbiota; microbiota manipulation strategies.

Figure 1

Multi-organ involvement in cancer cachexia. Apart from the wasting of muscle and adipose tissues, cancer cachexia causes functional alterations in many other organs such as in the liver, intestine, blood circulation, heart, and brain.

Figure 2

Emerging strategies of gut microbiota manipulation for the supportive treatment of cancer cachexia. Since a certain number of studies showed associations between gut microbiota and cachexia, strategies of microbiota manipulation through the administration of probiotics, prebiotics, synbiotics, or through fecal microbiota transplantation (FMT) from healthy donors are emerging to correct dysbiosis and likely improve cachexia outcome.