The Role of Probiotics in Cancer Prevention

Abstract

The gut microbiome can play important role in maintaining homeostasis in the human body. An imbalance in the gut microbiome can lead to pro-inflammatory immune responses and the initiation of disease processes, including cancer. The research results prove some strains of probiotics by modulating intestinal microbiota and immune response can be used for cancer prevention or/and as adjuvant treatment during anticancer chemotherapy. This review presents the latest advances in research into the effectiveness of probiotics in the prevention and treatment support of cancer. The described issues concern to the anticancer activity of probiotic microorganisms and their metabolites. In addition, we described the potential mechanisms of probiotic chemoprevention and the advisability of using probiotics.

Keywords: anticancer activity; gut microbiome; probiotics.

Figure 1

Potential mechanisms of probiotics action in the prevention of colorectal cancer development. Symbols: ↓ decrease, ↑ increase.

Figure 2

The role of short-chain fatty acids (SCFAs) in regulation of gut and systemic immunity [99,100]. SCFAs are produced by intestinal microbiome in the fermentation of nondigestible carbohydrates (NDCs), undigested food fiber, or resistant starch (RS). SCFAs regulate intestinal barrier function by inducing intestinal epithelial cell secretion of interleukin-18 (IL-18), mucin (MUC2), antimicrobial peptides, and upregulating the expression of tight junction. Moreover, SCFAs regulate the T cell function through G-protein-coupled receptors (GPR41, GPR43, GPR109A), Olfr78 receptor signaling, and through inhibition of histone deacetylase (HDAC) which affects inhibition of nuclear factors (nuclear factor-κB; NF-κB). SCFAs play an important role in inducing neutrophils migration to inflammatory site and enhancing their phagocytosis. Moreover, SCFAs inhibit intestinal macrophage production of proinflammatory cytokines (e.g., IL-6, IL-8, IL-1β and TNFα), and possibly induce intestinal IgA production of B cells. SCFAs affect the differentiation of regulatory T (Treg) cells and the production of interleukin-10 (IL-10). The direct impact of SCFA as well as SCFA regulation of dendritic cells (DCs) are mediated in the differentiation of T cells. SCFAs regulate the generation of Treg, Th1, and Th17 in different cytokine environment. SCFAs promote apoptosis and suppress proliferation of tumor cells resulting in inhibiting the carcinogenesis. Abbreviations: Aldh1A2—aldehyde dehydrogenase 1A2. Symbols:→ activation; →inhibition.

Figure 3

Potential mechanisms of action of lactic acid bacteria in pathways of apoptosis [50,107]. The extrinsic pathway is initiated by FAS ligand-induced activation of death receptors on the cell membrane (e.g., TNF—tumor necrosis factor). The intrinsic pathway is induced radiotherapy and chemotherapy. The mitochondrial localization and activation of Bax and Bak are required in the intrinsic pathway. However, it can be prevented by pharmacologic inhibitors or anti-apoptotic Bcl-2 family proteins. Lactic acid bacteria can enhance the apoptosis induction through 5-fluorouracile (5-FU) that can induce the activation of autophagic cell death promoted by the induction of Beclin-1 and GRP78 or Bcl-2 and Bak. Moreover, LAB may act to prevent cancer via downregulating NF-κB-dependent gene products which regulate cell survival (Bcl-2, Bcl-xl) and proliferation (Cox-2, cyclin D1). Symbols: →activation; →inhibition.