Postbiotics, Metabolic Signaling, and Cancer

Abstract

Postbiotics are health-promoting microbial metabolites delivered as a functional food or a food supplement. They either directly influence signaling pathways of the body or indirectly manipulate metabolism and the composition of intestinal microflora. Cancer is the second leading cause of death worldwide and even though the prognosis of patients is improving, it is still poor in the substantial part of the cases. The preventable nature of cancer and the importance of a complex multi-level approach in anticancer therapy motivate the search for novel avenues of establishing the anticancer environment in the human body. This review summarizes the principal findings demonstrating the usefulness of both natural and synthetic sources of postbotics in the prevention and therapy of cancer. Specifically, the effects of crude cell-free supernatants, the short-chain fatty acid butyrate, lactic acid, hydrogen sulfide, and β-glucans are described. Contradictory roles of postbiotics in healthy and tumor tissues are highlighted. In conclusion, the application of postbiotics is an efficient complementary strategy to combat cancer.

Keywords: GPR81; SCFA; colorectal cancer; functional food; intestinal metabolome; microbiome.

Figure 1

Signaling response of non-cancer (a) and cancer cell (b) to postbiotics (AMPK—5’ AMP-activated protein kinase, H₂S—hydrogen sulfide, Keap1—Kelch Like ECH Associated Protein 1, LBK1—liver kinase B1, Nrf-2—Nuclear factor erythroid 2-related factor 2, PGC1α—Peroxisome proliferator-activated receptor gamma coactivator 1-alpha, SIRT1—Sirtuin 1).

Figure 2

Import and metabolism of butyrate in non-cancer (a) and cancer cell (b) (BCRP—breast cancer resistance protein, BUT—butyrate, CIT—citrate, HDACs—histone deacetylases, MCT—monocarboxylate transporter, GLC—glucose, LAC—lactate, PYR—pyruvate, TCA—tricarboxylic acid cycle).

Figure 3

Synthesis and metabolism of H₂S in the cancer cell (α-KG—alpha-ketoglutarate, H₂S—hydrogen sulfide, CAT—cysteine: 2-oxoglutarate aminotransferase, CBS—cystathionine beta-synthase, CSE—cystathionine gamma-lyase, cys—cysteine, MPTS—3-mercaptopyruvate sulfurtransferase).

Figure 4

Mechanism of β-glucans action (CD—complement domain, CR—complement receptor, Ig—immunoglobulin).