The brain–gut–microbiome axis is a bidirectional communication pathway between the gut microbiota and the central nervous system. The growing interest in the gut microbiota and mechanisms of its interaction with the brain has contributed to the considerable attention given to the potential use of probiotics, prebiotics and postbiotics in the prevention and treatment of depressive disorders. This review discusses the up-to-date findings in preclinical and clinical trials regarding the use of pro-, pre- and postbiotics in depressive disorders. Studies in rodent models of depression show that some of them inhibit inflammation, decrease corticosterone level and change the level of neurometabolites, which consequently lead to mitigation of the symptoms of depression. Moreover, certain clinical studies have indicated improvement in mood as well as changes in biochemical parameters in patients suffering from depressive disorders.
Ovarian cancer (OC) is usually diagnosed at an advanced stage and is related with poor prognosis. Despite numerous studies, the pathogenesis of OC is still unknown. Recent studies indicate the role of the immune system in the development and spread of OC. The identification of factors and mechanisms involved in that process and their modulation is crucial for creating effective antitumor therapy. We investigated the potential role of Th17 cells in OC patients (n = 71) by analyzing the frequencies of Th17 cells in three different environments, i.e., peripheral blood (PB), peritoneal fluid (PF), and tissue (Th17 infiltrating cells), and the concentration of IL-17A in plasma and PF of patients in terms of their clinical and prognostic significance. Th17 cells were analyzed by flow cytometry as a percentage of CD4+ lymphocytes that expressed intracellular expression of IL-17A. The level of IL-17A in plasma and PF were determined by ELISA. Our results showed accumulation of Th17 cells among tumor-infiltrating CD4+ lymphocytes (p<0.001 in relation to PB). Moreover, the percentage of Th17 cells in both PB and PF of OC patients was significantly lower than that in benign tumors group (n = 35). There were no significant differences in the percentage of Th17 cells in PB, PF, and tissue in relation to clinicopathological characteristics of OC patients and survival. The lower percentage of Th17 cells in the PB and PF of OC patients may promote evasion of host immune response by cancer cells. The concentration of IL-17A in plasma of OC patients was higher (p<0.0001) than that in both benign tumors and control group (n = 10). The PF IL-17A level in OC patients was higher (p<0.0001) than that in women with benign ovarian tumors, indicating its synthesis in OC microenvironment. Higher IL-17A level in PF is correlated with longer (median: 36.5 vs. 27 months) survival of OC patients.
The latest literature demonstrates the predominant role of the programmed cell death axis (PD-1/PD-L1/PD-L2) in ovarian cancer (OC) pathogenesis. However, data concerning this issue is ambiguous. Our research aimed to evaluate the clinical importance of PD-L1/PD-L2 expression in OC environments. We evaluated the role of PD-L1/PD-L2 in OC patients (n = 53). The analysis was performed via flow cytometry on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) and monocytes/macrophages (MO/MA) in peripheral blood, peritoneal fluid (PF), and tumor tissue (TT). The data were correlated with clinicopathological characteristics and prognosis of OC patients. The concentration of soluble PD-L1 (sPD-L1) and PD-1 in the plasma and PF were determined by ELISA. We established an accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the tumor microenvironment. We showed an elevated level of sPD-L1 in the PF of OC patients in comparison to plasma and healthy subjects. sPD-L1 levels in PF showed a positive relationship with Ca125 concentration. Moreover, we established an association between higher sPD-L1 levels in PF and shorter survival of OC patients. An accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the TT and high sPD-L1 levels in PF could represent the hallmark of immune regulation in OC patients.
Ovarian cancer (OC) is one of the deadliest gynecological cancers. Recent studies suggest a crucial role of inflammatory immune system cells in the progression and metastasis of OC. The understanding of inflammatory mechanisms is pivotal for the selection of a biomarker that allows the differentiation between malignant and benign tumors, monitoring the progression of the disease, and identification of patients that will respond to implemented treatment. Our study is aimed at evaluating the profile of IL-6 in the plasma and peritoneal fluid (PF) of patients with various clinical manifestations of OC (n=78). We also examined the relationship between IL-6 and PD-L1/PD-L2 positive CD45+CD14+ inflammatory cell (MO/MA) levels in three OC environments (TME): peripheral blood (PB), PF, and tumor (TT) and their clinical and prognostic relevance in OC patients. The expression of PD-L1/PD-L2 molecules was analyzed by flow cytometry. The IL-6 levels were determined by ELISA. We found an elevated level of PD-L1/PD-L2 positive MO/MA in TT compared to PB (p<0.0001). Significantly higher (p<0.0001) levels of IL-6 were observed in PF of the OC patients than in the benign ovarian tumor group (n=31). Additionally, we found higher IL-6 levels in PF than in the plasma of the OC patients. Interestingly, accumulation of IL-6 was observed in PF of patients with low-differentiated OC and correlated with worse prognosis. Moreover, we observed correlations between the level of IL-6 and CD45+CD14+ cells and between CD45+CD14+PD-L1+ cells and the IL-6 level in PF. For the first time, we discovered that the higher percentage of CD45+CD14+PD-L2+ cells in PF predicts better survival of OC patients. Our study suggests that CD45+CD14+PD-L2+ cells and IL-6 may be predictive biomarkers for OC patients. Understanding how the composition of TME changes during OC development and progression is a prerequisite for projecting new therapeutic strategies. Overall, further validation research is warranted.
The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain–gut–microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites’ levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.
Recently, the intensive development of immunotherapies in the treatment of malignant tumors has been observed. The investigated treatment approaches including specific monoclonal antibodies, adoptive therapy and also anticancer vaccinations. The implementation of immunotherapy seems to be promising in treatment of the most malignant and fatal tumors including ovarian cancer. However, current findings have shown only a nonsignificant improvement of patients’ survival. The possible cause of failure may be immunotherapy barriers that are a result of low immunogenicity level of ovarian cancer cells, mutation variability, and also the presence of a specific, immunosuppressive tumor microenvironment, which stimulates the cancer progression. The review presents the selected mechanisms of tumor resistance to immunological therapy. In order to project effective treatment approaches, it is necessary to understand both, mechanisms leading to the correct response for the treatment and causing therapeutic failures, resulting from resistance to therapy.
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