Emre Evin

Background and Objective: Ensuring colon homeostasis is of significant influence on colon cancer and delicate balance is maintained by a healthy human gut microbiota. Probiotics can modulate the diversity of the gut microbiome and prevent colon cancer. Metabolites/byproducts generated by microbial metabolism significantly impact the healthy colonic environment. Hesperidin is a polyphenolic plant compound well known for its anticancer properties. However, low bioavailability of hesperidin after digestion impedes its effectiveness. CYP2W1 is a newly discovered oncofetal gene with an unknown function. CYP2W1 gene expression peaks during embryonic development and is suddenly silenced immediately after birth. Only in the case of some types of cancer, particularly colorectal and hepatocellular carcinomas, this gene is reactivated and its expression is correlated with the severity of the disease. This study aimed to investigate the effects of hesperidin-treated Lacticaseibacillus rhamnosus GG (LGG) cell-free supernatants on CaCo2 colon cancer cell viability and CYP2W1 gene expression. Methods: Alamar Blue cell viability assay was used to investigate the cytotoxic effect of cell-free supernatant of LGG grown in the presence of hesperidin on CaCo2 cells. To observe the effect of cell-free supernatants of LGG on the expression of CYP2W1 gene, qRT-PCR was performed. Results: Five times diluted hesperidin treated cell-free supernatant (CFS) concentration considerably reduced CaCo2 colon cancer cell viability. Furthermore, CYP2W1 gene expression was similarly reduced following CFS treatments and nearly silenced under probiotic bacteria CFS treatment. Conclusion: The CYP2W1 gene expression was strongly reduced by cell-free supernatants derived from LGG culture, with or without hesperidin. This suggests that the suppression may be due to bacterial byproducts rather than hesperidin. Therefore, the CYP2W1 gene in the case of deregulation of these metabolites may cause CYP2W1-related colon cancer cell proliferation.

Background Patients with multiple sclerosis (MS) have significantly lower vitamin D levels. Cholesterol is known to be the precursor for vitamin D synthesis, and cholesterol removal is regulated by cholesterol 7α-hydroxylase (CYP7A1) in the liver and cholesterol 24S-hydroxylase (CYP46A1) in the brain. In this study, single nucleotide polymorphisms (SNPs) within the genes CYP7A1 (rs3808607) and CYP46A1 (rs754203) were investigated for their effects on serum lipid profiles, vitamin D levels, and the risk of developing MS. Methods Patients with MS (n = 191) and controls (n = 100) were tested using the PCR–RFLP method to determine their genotypes for rs3808607 and rs754203 SNPs. Results The minor (C) allele frequency for CYP7A1 rs3808607 variation was 0.380 in patients with MS and 0.305 in control subjects (P = .074). For CYP46A1 rs754203, the frequencies of the minor (C) allele were 0.272 and 0.250 in patients and control subjects, respectively (P = .563). Serum vitamin D (25(OH)D3) concentrations were significantly lower in patients than in control subjects (P = .002). The CYP46A1 rs754203 SNP was associated with total cholesterol levels in patients, whereas the CYP7A1 rs3808607 variant was not associated with serum lipid parameters or vitamin D levels in patients or control subjects. Conclusion CYP7A1 rs3808607 and CYP46A1 rs754203 variations are not likely to confer an independent risk for MS development in the Turkish population. To the best of our knowledge, this is the first study to investigate the association between CYP46A1 rs754203 and MS risk.

Functional foods are groups of foods that have potentially positive effects on health beyond basic nutrition. Probiotics are beneficial microorganisms, being as a group of functional foods, and when ingested in adequate amounts, they possess positive health effects to host organisms. Lactobacillus acidophilus and Lactobacillus rhamnosus are two of the most studied and very well-known probiotic bacteria. They can have anti-carcinogenic functions, yet their exact mechanisms how they possess anti-carcinogenic activities are still under investigation. Another group of functional foods is plant-based phenolic compounds. They also have potential to possess anti-carcinogenic activities. Among them, oleuropein is very interesting and well-known phenolic compound naturally present in olive fruits and olive oil. As the phenolic compounds and probiotic bacteria can be present at the same time in human gastrointestinal tract, this study aims to investigate the in vitro cytotoxic effects of Lactobacillus acidophilus LA-5 (LA-5) and Lactobacillus rhamnosus GG (GG) grown in the presence of oleuropein on human prostate cancer cell line. To achieve this purpose, oleuropein was added to media of these bacteria and effects of cell-free supernatants of these combinations (phenolic+probiotic) on cytotoxicity of prostate cancer cell line PC-3 were investigated using MTT Method. Concentrations of 0, 50, 100, and 250 µg/mL of oleuropein were added to bacterial cultures and no inhibition on growths of LA-5 or GG were observed. Cell surface hydrophobicity (i.e., adhesion to hydrophobic solvents) is an important feature for bacteria to be retained in gastrointestinal tract (GIT). MATS tests showed all concentrations of oleuropein decreased the surface hydrophobicity of GG, while a dose-dependent increase or decrease in surface hydrophobicity was observed in LA-5. Bacterial aggregation is defined as clustering of bacteria. Auto-aggregation studies showed oleuropein affected the aggregation of bacteria in a dose-dependent manner. Oleuropein added to the growth medium of LA-5 had additional effects on the cytotoxicity of cell-free supernatants of this bacterium. However, addition of oleuropein to the growth medium of GG did not show significant changes on the cytotoxicity of cell-free supernatants of this bacterium. Thus, the results indicate that new combinations of functional foods have potential to formulate new nutraceuticals.