Probiotics and suppression of cancer

Probiotics are ‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host’. The popularity of probiotics has expanded exponentially recently, because of their health-promoting effects and their abilities to prevent or treat different diseases, including some types of cancers. These include microbiota modulation, immune modulation, reduced bacterial translocation, enhanced gut barrier function, anti-inflammatory and antipathogenic activity, with effects on reducing tumor formation and metastasis. The composition of gut microbiota has been associated with colon cancer risk. For instance, Fusobacterium nucleatum, Streptococcus gallolyticus and more recently Providencia have been found in human colorectal cancer tumors. Concerning the mechanism of action, some studies reported that such suppressive effect was dependent on short chain fatty acids (SCFAs) production of probiotics. Apart from SCFA, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that induced apoptosis of tumors was also found to be upregulated by Lactobacillus casei ATCC 393, and the increased protein expression of TRAIL in tumors was associated with decreased tumor incidence in mice. In most studies, tumors were either induced through administration of carcinogens, for example 1,2-dimethylhydrazine dihydrochloride or azoxymethane (AOM), or introduced through injection of tumor cells.Previous in-vitro studies have shown that proliferation of breast cancer cells, Michigan Cancer Foundation-7 (MCF-7), was inhibited by different isolated probiotics strain/supernatant from probiotic cultures. It was also reported that live Enterococcus faecalis and Staphylococcus hominis isolated from breast milk, as well as heat-killed cells and cytoplasmic fractions, caused cytotoxicity through the induction of apoptosis and G0/G1 phase cell cycle arrest Apart from the involvement of immune system, hypoxia-inducible factor (HIF) pathway that is associated with breast cancer was also reported to be suppressed by Lactobacillus cultures supernatant eight different Lactobacillus strains exerted the anti-proliferative effect on leukemia cells. Most of the heat-killed bacteria, cell wall extract and genomic DNA of the selected strains showed inhibition toward leukemia cells.Administration of Bacteroides fragilis restored the CTLA-4 blockade effect, by affecting the interleukin (IL)-12- dependent Th1 immune response. Researchers reported a greater anti-melanoma effect of combined treatment of Bifidobacterium and programmed cell death-ligand 1 (PD-L1) blockade therapy, when compared with individual treatment.Bifidobacterium species were suggested to exhibit protective effects through the activation of dendritic cells and thus the enhancement of antitumor immune response. Stimulation of T-cell responses was involved as revealed by the increased level of tumor-specific and antigen-specific T cells level. The probiotics mixture reduced Th17 cells frequency and its recruitment to tumor, leading to a decreased production of IL-17. As IL-17A produced from Th17 favors angiogenesis, reduction of Th17 and IL-17 level may contribute to inhibition of cancer progression.Human clinical trials of the application of probiotics as bio therapeutics against cancer are still lacking. Extensive clinical trials are necessary to identify potential strains, dosages and administration regimes for specific types and stages of cancer.