The ability to perform effectively in the gastrointestinal tract (GIT) is one of the most significant criteria in the selection of potential probiotic bacteria. Thus, the present study aimed to investigate the potential probiotic characteristics of some selected lactic acid bacteria (LAB) isolated from vegetable products. Probiotic characteristics included tolerance to acid and bile, cholesterol-removing ability, bile salt hydrolysis, resistance against lysozyme and antibiotics, production of exopolysaccharides (EPS), antimicrobial and hemolytic activities, and cell surface characteristics (auto-aggregation, co-aggregation, and hydrophobicity). The survival rate of isolates after G120 ranged from 8.0 to 8.6 Log₁₀ CFU/mL. After the intestinal phase (IN-120), the bacterial count ranged from 7.3 to 8.5 Log₁₀ CFU/mL. The bile tolerance rates ranged from 17.8 to 51.1%, 33.6 to 63.9%, and 55.9 to 72.5% for cholic acid, oxgall, and taurocholic acid, respectively. Isolates F1, F8, F23, and F37 were able to reduce cholesterol (>30%) from the broth. The auto-aggregation average rate increased significantly after 24 h for all isolates, while two isolates showed the highest hydrophobicity values. Moreover, isolates had attachment capabilities comparable to those of HT-29 cells, with an average of 8.03 Log₁₀ CFU/mL after 2 h. All isolates were resistant to lysozyme and vancomycin, and 8 out of the 17 selected isolates displayed an ability to produce exopolysaccharides (EPS). Based on 16S rRNA sequencing, LAB isolates were identified as Enterococcus faecium, E. durans, E. lactis, and Pediococcus acidilactici.

Honey has exerted a high impact in the field of alternative medicine over many centuries. In addition to its wound healing, anti-microbial and antioxidant properties, several lines of evidence have highlighted the efficiency of honey and associated bioactive constituents as anti-tumor agents against a range of cancer types. Mechanistically, honey was shown to inhibit cancer cell growth through its pro-apoptotic, anti-proliferative and anti-metastatic effects. However, the potential of honey to regulate anti-tumor immune responses is relatively unexplored. A small number of in vitro and in vivo studies have demonstrated the ability of honey to modulate the immune system by inducing immunostimulatory as well as anti-inflammatory effects. In the present review, we summarize the findings from different studies that aimed to investigate the immunomodulatory properties of honey and its flavonoid components in relation to cancer. While these studies provide promising data, additional research is needed to further elucidate the immunomodulatory properties of honey, and to enable its utilization as an adjuvant therapy in cancer.

Aberrantly high levels of tyrosine-phosphorylated signal transducer and activator of transcription 3 (p-STAT3) are found constitutively in ~50% of human lung and breast cancers, acting as an oncogenic transcription factor. We previously demonstrated that Manuka honey (MH) inhibits p-STAT3 in breast cancer cells, but the exact mechanism remained unknown. Herein, we show that MH-mediated inhibition of p-STAT3 in breast (MDA-MB-231) and lung (A549) cancer cell lines is accompanied by decreased levels of gp130 and p-JAK2, two upstream components of the IL-6 receptor (IL-6R) signaling pathway. Using an ELISA-based assay, we demonstrate that MH binds directly to IL-6Rα, significantly inhibiting (~60%) its binding to the IL-6 ligand. Importantly, no evidence of MH binding to two other cytokine receptors, IL-11Rα and IL-8R, was found. Moreover, MH did not alter the levels of tyrosine-phosphorylated or total Src family kinases, which are also constitutively activated in cancer cells, suggesting that signaling via other growth factor receptors is unaffected by MH. Binding of five major MH flavonoids (luteolin, quercetin, galangin, pinocembrin, and chrysin) was also tested, and all but pinocembrin could demonstrably bind IL-6Rα, partially (30–35%) blocking IL-6 binding at the highest concentration (50 μM) used. In agreement, each flavonoid inhibited p-STAT3 in a dose-dependent manner, with estimated IC₅₀ values in the 3.5–70 μM range. Finally, docking analysis confirmed the capacity of each flavonoid to bind in an energetically favorable configuration to IL-6Rα at a site predicted to interfere with ligand binding. Taken together, our findings identify IL-6Rα as a direct target of MH and its flavonoids, highlighting IL-6R blockade as a mechanism for the anti-tumor activity of MH, as well as a viable therapeutic target in IL-6-dependent cancers.

Current modalities of cancer treatment have limitations related to poor target selectivity, resistance to treatment, and low response rates in patients. Accumulating evidence over the past few decades has demonstrated the capacity of several strains of bacteria to exert anti-tumor activities. Salmonella is the most extensively studied entity in bacterial-mediated cancer therapy, and has a good potential to induce direct tumor cell killing and manipulate the immune components of the tumor microenvironment in favor of tumor inhibition. In addition, Salmonella possesses some advantages over other approaches of cancer therapy, including high tumor specificity, deep tissue penetration, and engineering plasticity. These aspects underscore the potential of utilizing Salmonella in combination with other cancer therapeutics to improve treatment effectiveness. Herein, we describe the advantages that make Salmonella a good candidate for combination cancer therapy and summarize the findings of representative studies that aimed to investigate the therapeutic outcome of combination therapies involving Salmonella. We also highlight issues associated with their application in clinical use.

The gastrointestinal (GI) tract of multicellular organisms, especially mammals, harbors a symbiotic commensal microbiota with diverse microorganisms including bacteria, fungi, viruses, and other microbial and eukaryotic species. This microbiota exerts an important role on intestinal function and contributes to host health. The microbiota, while benefiting from a nourishing environment, is involved in the development, metabolism and immunity of the host, contributing to the maintenance of homeostasis in the GI tract. The immune system orchestrates the maintenance of key features of host–microbe symbiosis via a unique immunological network that populates the intestinal wall with different immune cell populations. Intestinal epithelium contains lymphocytes in the intraepithelial (IEL) space between the tight junctions and the basal membrane of the gut epithelium. IELs are mostly CD8⁺ T cells, with the great majority of them expressing the CD8αα homodimer, and the γδ T cell receptor (TCR) instead of the αβ TCR expressed on conventional T cells. γδ T cells play a significant role in immune surveillance and tissue maintenance. This review provides an overview of how the microbiota regulates γδ T cells and the influence of microbiota-derived metabolites on γδ T cell responses, highlighting their impact on immune homeostasis. It also discusses intestinal neuro-immune regulation and how γδ T cells possess the ability to interact with both the microbiota and brain.