Gut Microbiota and Cancer: From Pathogenesis to Therapy

Abstract

Cancer is a multifactorial pathology and it represents the second leading cause of death worldwide. In the recent years, numerous studies highlighted the dual role of the gut microbiota in preserving host's health. Gut resident bacteria are able to produce a number of metabolites and bioproducts necessary to protect host's and gut's homeostasis. Conversely, several microbiota subpopulations may expand during pathological dysbiosis and therefore produce high levels of toxins capable, in turn, to trigger both inflammation and tumorigenesis. Importantly, gut microbiota can interact with the host either modulating directly the gut epithelium or the immune system. Numerous gut populating bacteria, called probiotics, have been identified as protective against the genesis of tumors. Given their capability of preserving gut homeostasis, probiotics are currently tested to help to fight dysbiosis in cancer patients subjected to chemotherapy and radiotherapy. Most recently, three independent studies show that specific gut resident species may potentiate the positive outcome of anti-cancer immunotherapy. The highly significant studies, uncovering the tight association between gut microbiota and tumorigenesis, as well as gut microbiota and anti-cancer therapy, are here described. The role of the Lactobacillus rhamnosus GG (LGG), as the most studied probiotic model in cancer, is also reported. Overall, according to the findings here summarized, novel strategies integrating probiotics, such as LGG, with conventional anti-cancer therapies are strongly encouraged.

Keywords: Lactobacillus rhamnosus GG; anti-cancer therapy; cancer; inflammasomes; integrated therapy; microbiome; microbiota; probiotics.

Figure 1

Anti-tumoral effects of the gut microbiota. Probiotics and other gut resident bacteria are able to secrete molecules, capable, in turn, to fight tumor growth and prevent tumorigenesis through several mechanisms. Schematic of the intestinal layers, from top to bottom: mucus and microbiota, gut epithelium. Into the grey boxes are illustrated, from top to bottom, the microorganism species implicated in the anti-cancer process, the molecules produced and the corresponding effects induced within the host. Abbreviations: MPL, monophosphoryl lipid A; LPS, lipopolysaccharide.

Figure 2

Pro-tumoral effects of the gut microbiota. Bacteria prominent during gut dysbiosis can secrete toxins able to interfere with host cell growth, finally predisposing the host organism to cancer development. Schematic of the intestinal layers, from top to bottom: mucus and microbiota, gut epithelium. Into the grey boxes are illustrated, from top to bottom, the microorganism species implicated in the pro-cancer process, the molecules produced and the corresponding effects induced within the host. Abbreviations: ROS, Reactive Oxygen Species; CTD, cytolethal distending toxin; IpgD, inositol phosphate phosphatase D; VirA, virulence gene A; CagA, cytotoxin associated gene A; FadA, Fusobacterium effector adhesin A; MP Toxin, metalloproteinase toxin; AvrA, avirulence protein A; β-gluc, β-glucuronidase.

Figure 3

Role of probiotics in anti-cancer therapy. Probiotics and Fecal Microbiome Transplantation (FMT) are currently studied as anti-cancer adjuvants to fight dysbiosis following anti-cancer therapy, to increase chemotherapy and immunotherapy efficacy and to both reduce tumor mass and prevent tumor recurrence.