The human body contains many microorganisms, including a large number of bacteria, viruses, fungi, and protozoa, which are referred to as the microbiota. Compared with the number of cells comprising the human body, that of the microbiota has been found to be much larger. The microbiome is defined as microorganisms and their genomes and has been shown to contain about 100 times more genes than the human genome. The microbiota affects many vital functions in the human body. It contributes to regulation of the immune system, digestion of food, production of vitamins such as B12 and K, metabolization of xenobiotic materials, and many other tasks. Many factors affect the microbiota biodiversity, such as diet, medicines including antibiotics, relationships with the environment, pregnancy, and age. Studies have shown that the lack of microbiota diversity leads to many diseases like autoimmune diseases such as diabetes type I, rheumatism, muscular dystrophy, problems in blood coagulation due to lack of vitamin K, and disturbances in the transfer of nerve cells due to lack of vitamin B12, in addition to its involvement in a number of conditions such as cancer, memory disorders, depression, stress, autism, and Alzheimer’s disease. The aim of this review is to summarize the latest studies discussing the relationship between the microbiota and the human body in health and diseases.

Globally colorectal cancer ranks as the third most widespread disease and the third leading cause of cancer-associated mortality. Immunotherapy treatments like PD-L1 blockade have been used to inhibit the PD-L1 legend, which boosts the activity of cytotoxic T lymphocytes. Recently, studies suggest that some probiotics could potentially enhance the effectiveness of immunotherapy treatments for cancer patients. We found that in Caco-2 and HT-29 cells, the live Leuconostoc mesenteroides treatment resulted an increase in the PD-L1 expression and this treatment stimulated interferon-gamma (IFN-γ) production in Jurkat T-cells. Due to the well-established ability of IFN-γ to enhance PD-L1 expression, the combination of IFN-γ and L. mesenteroides was used in colon cancer cell lines and a resulting remarkable increase of over tenfold in PD-L1 expression was obtained. Interestingly, when L. mesenteroides and IFN-γ are present, the blockage of PD-L1 using PD-L1 antibodies not only improved the viability of Jurkat T-cells but also significantly boosted the levels of IFN-γ and IL-2, the T-cells activation marker cytokines. In addition to upregulating PD-L1, L. mesenteroides also activated Toll-like receptors (TLRs) and NOD-like receptors (NODs) pathways, specifically through TLR2 and NOD2, while also exerting a suppressive effect on autophagy in colon cancer cell lines. In conclusion, our findings demonstrate a significant upregulation of PD-L1 expression in colon cancer cells upon co-culturing with L. mesenteroides. Moreover, the presence of PD-L1 antibodies during co-culturing activates Jurkat T cells. The observed enhancement in PD-L1 expression may be attributed to the inhibition of the Autophagy pathway or activation of the hippo pathway. Graphical abstract text: The administration of Live Lactobacillus mesenteroides on colon cancer cells leads to the elevation of PD-L1, with a further increase observed in the presence of IFN-γ. Co-cultivation of Live L. mesenteroides with colon cancer cells in conjunction with anti-PD-L1 blockade antibody results in the enhanced viability of T cells. Key Points: Co-culturing L. mesenteroides increases PD-L1 gene and protein transaction in colon cancer. L. mesenteroides existing enhances T cells viability and activity. GPCR41/42 is a possible link between L. mesenteroides, YAP-1 and PD-L1.

Objective: The apoptotic effects of odoroside A on lung cancer cells were studied in our project. We also supported and extended our experimentally-proven results via bioinformatics analysis on human lung cancer tissues. Materials and Methods: In vitro studies were conducted using the A549 cell line. Cell proliferation was evaluated through a CCK-8 assay. For gene expression analysis, the qRT-PCR method was used, while CASP3 protein levels were detected using Western blotting and ELISA. Moreover, the oxidant status of cells was determined by measuring TAS and TOS levels. To construct a protein–protein interaction network, STRING analysis was performed. For the determination of differential expression of apoptosis-related genes, the GEPIA tool was utilized. Kaplan–Meier plots with overall survival, disease-specific survival and progression free intervals were obtained from UCSC Xena to evaluate the prognostic value of caspases. Results: The gene expression levels of CASP3, CASP7, CASP8, CASP9, FAS, and FADD were elevated between 4–16 fold in Odo A-treated lung cancer cells compared to controls. CASP3 protein expression was significantly higher in Odo A-treated cancerous cells than the control group. Low TAS (0.5700 ± 0.0067 in Odo A vs. 0.6437 ± 0.0151 in control) and high TOS (0.82800 ± 0.0208 in Odo A vs. 0.6263 ± 0.0258 in control) levels as well as high OSI values (1.4531 ± 0.0414 in Odo A vs. 0.9748 ± 0.0539 in control) were obtained. Correlogram and protein–protein network analyses suggested strong correlations and interactions among target genes. Lastly, Kaplan–Meier analysis showed no prognostic value of caspases, but potential therapeutic targets in lung cancer. Conclusions: Anti-cancer, prooxidative and therapeutic effects of Odo A on lung cancer cells were shown in our study. These data were supported and extended via computational analyses that we performed. In conclusion, Odo A could be used in clinics to treat patients with lung cancer.