The Effects and Mechanisms of Flavonoids on Cancer Prevention and Therapy: Focus on Gut Microbiota

Abstract

Flavonoids are a group of polyphenolic compounds which are ubiquitously found in plants and are consumed as part of the human diet in substantial amounts. The verification of flavonoids' cancer chemopreventive benefits has led to a significant interest in this field. Gut microbiota includes a diverse community of microorganisms and has a close relationship with cancer development. Increasing evidence has indicated that flavonoids exert anticarcinogenic effects by reshaping gut microbiota. Gut microbiota can convert flavonoids into bioactive metabolites that possess anticancer activity. Here, we present a brief introduction to gut microbiota and provide an overview of the interplay between gut microbiota and cancer pathogenesis. We also highlight the crucial roles of flavonoids in preventing cancer based on their regulation of gut microbiota. This review would encourage research on the flavonoid-intestinal microbiota interactions and clinical trials to validate the chemotherapeutic potentials of targeting gut microbiota by dietary bioactive compounds.

Keywords: bioactive metabolites; cancer; chemopreventive benefits; flavonoids; gut microbiota.

Figure 1

The mechanisms underlying gut microbiota dysbiosis-induced carcinogenesis. Host genotype, lifestyle, diet, infection, psychological stress and medications are important factors leading to intestinal dysbiosis. Gut microbiota dysbiosis drives carcinogenesis via different mechanisms, including induction of DNA damage, production of tumor-promoting metabolites, regulation of diverse signaling pathways, manipulation of host immune responses, activation of chronic inflammation and promotion of oncogenic bacteria infection.

Figure 2

Categorization, food sources, representatives and chemical structures of flavonoids. Flavonoids are naturally present in fruits, vegetables and plant-derived beverages. Based on their chemical structures, flavonoids are generally classified into seven main groups including anthocyanidins, chalcones, flavanols, flavanones, flavonols, flavones and isoflavones.

Figure 3

Schematic illustration of the beneficial effects of flavonoids against cancer via regulating gut microbiota. Flavonoids ameliorate gut microbiota dysbiosis by elevating the abundance of beneficial microbial organisms and reducing the counts of opportunistic pathogenic species. As a result, flavonoid-mediated modulation of gut microbiota contributes to prevention of cancer cell proliferation, invasion and metastasis. Flavonoids also promote cancer cell death and enhance chemotherapeutic sensitivity of cancer cells by reverting imbalanced gut microbiota. Furthermore, gut microbiota can transform flavonoids into bioactive metabolites that show anticancer activities.