Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies

Abstract

Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.

Comparison of the gut microbiota composition between the wild and captive Tibetan wild ass ( Equus kiang )

“…In the wild, due to food shortage, protein and fat intake decreased, and the Bacteroidetes content increased to help host to increase their nutrition. A disruption of the symbiosis between the microbiota and host is known as dysbiosis and is described in multiple chronic diseases, such as obesity and malnutrition (Castaner et al 2018;Zhang et al 2018;Jeong et al 2019), neurological disorders (Kurokawa et al 2018;Quagliariello et al 2018;Sun and Shen 2018), inflammatory bowel disease (IBD) (Costa et al 2012;Roche-Lima et al 2018), metabolic syndrome (Zhao et al 2018), cancer and other diseases (Katsimichas et al 2018;Lu et al 2018;Panebianco et al 2018;Pulikkan et al 2018;Zitvogel et al 2018). We presume that the health of the wild group of Tibetan wild asses was better than the captive group.…”

Mutational signatures shift induced by chemotherapeutic agents, 5-Fluorouracil and Oxaliplatin, in the gut microbiome

“…The human gut microbiota is highly complex and exists in a dynamic balance between symbiosis and pathogenesis, which can influence almost any aspect of host physiology [28]. Growing evidence suggests that the gut microbiota not only plays a key role in carcinogenesis but also influences the efficacy and toxicity of anticancer therapy [29,30]. The microbiota modulates the host response to chemotherapy via numerous mechanisms, such as alteration of community structure and immune microenvironment.…”

Inhibition of pyruvate dehydrogenase kinase influence microbiota and metabolomic profile in pancreatic cancer xenograft mice

“…The study of the microbiota has attracted increasing attention during the last decade since it has become clear that the composition and function of this ecological community of commensal, symbiotic and pathogenic microorganisms affect several physiological and pathological processes, including cancer [13]. Although microbiota is relatively stable over time [14] it can be easily modi ed by a number of environmental factors, such as lifestyle, diet and drugs [15,16,17]. The current study shows that DCA treatment led to several shifts on the microbiota in particular at family, genus or species level in pancreatic cancer xenograft mice.…”