Showing papers by "Meirav Pevsner-Fischer published in 2016"

Role of the microbiome in non-gastrointestinal cancers.

Abstract: "The forgotten organ", the human microbiome, comprises a community of microorganisms that colonizes various sites of the human body. Through coevolution of bacteria, archaea and fungi with the human host over thousands of years, a complex host-microbiome relationship emerged in which many functions, including metabolism and immune responses, became codependent. This coupling becomes evident when disruption in the microbiome composition, termed dysbiosis, is mirrored by the development of pathologies in the host. Among the most serious consequences of dysbiosis, is the development of cancer. As many as 20% of total cancers worldwide are caused by a microbial agent. To date, a vast majority of microbiome-cancer studies focus solely on the microbiome of the large intestine and the development of gastrointestinal cancers. Here, we will review the available evidence implicating microbiome involvement in the development and progression of non-gastrointestinal cancers, while distinguishing between viral and bacterial drivers of cancer, as well as "local" and "systemic", "cancer-stimulating" and "cancer-suppressing" effects of the microbiome. Developing a system-wide approach to cancer-microbiome studies will be crucial in understanding how microbiome influences carcinogenesis, and may enable to employ microbiome-targeting approaches as part of cancer treatment.

Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5(+) B regulatory cells.

Abstract: To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5+ B cells in MSC therapy. The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4+ T helper (Th) cell subgroups and CD5+ regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5+ B cells were isolated for in vitro co-culture and adaptive transfer. HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5+ B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5+ B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5+ B cells also inhibited T-cell proliferation and produced interleukin (IL)-10. HUC-MSCs protected against experimental colitis by boosting the numbers of CD5+ B cells and IL-10-producing CD5+ Bregs, and correcting Treg/Th17/Th1 imbalances.

The Microbiota and Its Modulation in Immune-Mediated Disorders

Abstract: Bacteria, viruses, archaea, and fungi inhabiting the mucosal surfaces of the human body are collectively termed the microbiota, and have coevolved with the human body for millions of years. This has resulted in the development of diverse and extensive host–microbiota interactions, influencing multiple physiological processes, including metabolism and normal development and function of the immune system. The densest microbiota resides in the mammalian gastrointestinal (GI) tract, where it forms a diverse community of trillions of microorganisms, now believed to be an integral part of the human holobiome. While comprising only 1–3% of the total body mass, an individual’s gut microbiota cells and genes outnumber those of the human body’s cells by a ratio of up to 10:1 and 100:1, respectively. Bacterial composition varies along the GI tract, as each species colonizes a specific niche. Disruption of the microbial community, termed dysbiosis, is suggested to constitute a major risk factor for an increasing array of diseases, including susceptibility to common multifactorial disorders such as obesity and its complications, infection, auto-inflammation, metabolic homeostasis, and even cancer. In this chapter we will provide an overview of the establishment of the gut microbiota during human development, describe how it influences the establishment and normal functions of the host immune system, and the means by which we can control and alter its composition and function. We will then focus on a few examples demonstrating how dysbiotic microbiota composition and function may affect the pathogenesis of various immune-mediated disorders. The emerging data presented in this review suggests that interventions affecting microbiota functions and interactions with the host may be manipulated as future therapeutics targeting common immune-related disorders.