Probiotics and Probiotic-Derived Functional Factors-Mechanistic Insights Into Applications for Intestinal Homeostasis

Abstract

Advances in our understanding of the contribution of the gut microbiota to human health and the correlation of dysbiosis with diseases, including chronic intestinal conditions such as inflammatory bowel disease (IBD), have driven mechanistic investigations of probiotics in intestinal homeostasis and potential clinical applications. Probiotics have been shown to promote intestinal health by maintaining and restoring epithelial function, ensuring mucosal immune homeostasis, and inhibiting pathogenic bacteria. Recent findings reveal an approach for defining previously unrecognized probiotic-derived soluble factors as potential mechanisms of probiotic action. This review focuses on the impact of probiotics and probiotic-derived functional factors, including probiotic products and metabolites by probiotics, on the cellular responses and signaling pathways involved in maintaining intestinal homeostasis. Although there is limited information regarding the translation of probiotic treatment outcomes from in vitro and animal studies to clinical applications, potential approaches for increasing the clinical efficacy of probiotics for IBD, such as those based on probiotic-derived factors, are highlighted in this review. In this era of precision medicine and targeted therapies, more basic, preclinical, and clinical evidence is needed to clarify the efficacy of probiotics in maintaining intestinal health and preventing and treating disease.

Keywords: gut microbiota; immune response; inflammatory bowel disease; intestinal epithelium; intestinal homeostasis; probiotic-derived factor; probiotics.

Figure 1

The mechanisms of probiotic action. Probiotics contribute to maintaining homeostasis and prevention and/or treatment of diseases in host, including (1) blocking pathogenic bacterial effects by producing antibacterial substances and competing with pathogens for binding to epithelial cells; (2) promoting intestinal epithelial cell homeostasis by increasing barrier function, mucus production, survival, and cytoprotective responses; (3) defining the balance between necessary and excessive defense immunity by increasing innate immunity, such as production of IgA and defensin, up-regulating anti-inflammatory cytokine production, and inhibiting proinflammatory cytokine production; and (4) regulating the gut-brain axis through production of neurotransmitters and through the vagus nerve. DC, dendritic cell; IL, interleukin; HSP, heat shock protein.

Figure 2

Regulation of host responses by probiotic-derived factors. Several probiotic-derived factors, including products and metabolites, have been identified to exert health-promoting effects on the host. These functional factors of probiotics contribute to reinforcing intestinal barrier function and stimulating anti-inflammatory immune responses, leading to ameliorating intestinal inflammatory disorders.