Current and future pharmacotherapies for the management of constipation-predominant irritable bowel syndrome.

INTRODUCTION: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder affecting 9-23% of the world's population, with a higher prevalence among women. IBS is a complex disorder influenced by psychosocial, physiological, and genetic factors, exacerbated by stress. AREAS COVERED: Research confirms that the most common subtype of IBS is IBS-C. Therefore, new therapies are being developed to speed up bowel movement and reduce constipation, with drugs such as linaclotide, plecanatide, lubiprostone, or tegaserod available to reduce IBS-C symptoms. In addition, patients' condition is improved by foods rich in fiber and low in FODMAP and the use of biotics. EXPERT OPINION: The topic is of great importance due to the growing number of patients suffering from IBS-C and its significant impact on quality of life. Current clinical trials of new therapeutic options are not too successful, and it seems that one of the plausible treatment options could be the multi-drug cocktail with some, or perhaps even all its ingredients emerging from drug re-purposing. Another important path that needs to be explored further in IBS-C patients is the adjustment of dietary habits and/or introduction of dietary or nutritional intervention.

Mucosal-associated invariant T cells modulate innate immune cells and inhibit colon cancer growth.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we showed that peritumoral injection of in vivo-expanded MAIT cells into RAG1-/- mice with MC38-derived tumours inhibits tumour growth compared to control. Multiplex cytokine analyses showed that tumours from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting a potential association between eosinophil recruitment and tumour inhibition. In a human peripheral leukocyte co-culture model, we showed that leukocytes stimulated with MAIT ligand showed an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we showed that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy.

MAIT Cells Modulate Innate Immune Cells and Inhibit Colon Cancer Growth.

Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can be activated by microbial antigens and cytokines and are abundant in mucosal tissues including the colon. MAIT cells have cytotoxic and pro-inflammatory functions and have potentials for use as adoptive cell therapy. However, studies into their anti-cancer activity, including their role in colon cancer, are limited. Using an animal model of colon cancer, we show that peritumoral injection of in vivo-expanded MAIT cells into RAG1-/- mice with MC38-derived tumors inhibits tumor growth compared to control. Multiplex cytokine analyses show that tumors from the MAIT cell-treated group have higher expression of markers for eosinophil-activating cytokines, suggesting an association between eosinophil recruitment and tumor inhibition. In a human peripheral leukocyte co-culture model, we show that leukocytes stimulated with MAIT ligand show an increase in eotaxin-1 production and activation of eosinophils, associated with increased cancer cell killing. In conclusion, we show that MAIT cells have a protective role in a murine colon cancer model, associated with modulation of the immune response to cancer, potentially involving eosinophil-associated mechanisms. Our results highlight the potential of MAIT cells for non-donor restricted colon cancer immunotherapy.