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.
Highlights
The human gastrointestinal tract harbors a broad range of microbiota, which exhibit wide interpersonal differences in taxonomic composition while sharing a functional core set of specific microbial genes and metabolic modules [1, 2]
Research in humans and animal models has shown that metabolites and functional factors derived from the gut microbiota strongly impact the structural and functional maturation of the gastrointestinal tract, induction of immunotolerance, Probiotics in Intestinal Homeostasis neurodevelopment and homeostasis of intestinal epithelial cells, and functions of the immune and nervous systems in adulthood [reviewed in [3, 4]]
L. helveticus NS8 reduces plasma corticosterone and adrenocorticotropic hormone levels, increases plasma IL-10 levels, and restores hippocampal serotonin and norepinephrine levels and hippocampal brain-derived neurotrophic factor mRNA expression in chronic stress rats. These results indicate an antidepressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression, an effect that may be due to the microbiota–gut–brain axis [43]
Summary
The human gastrointestinal tract harbors a broad range of microbiota, which exhibit wide interpersonal differences in taxonomic composition while sharing a functional core set of specific microbial genes and metabolic modules [1, 2]. Studies on humans and animal models have revealed distinct cellular and molecular mechanisms of probiotic actions, including the blockage of pathogenic activities via the production of antibacterial substances and competitive inhibition of pathogen and toxin adherence to the intestinal epithelium; the regulation of immune responses via inhibited proinflammatory responses and enhanced anti-inflammatory immunity; the maintenance of intestinal epithelial homeostasis, such as the preservation of barrier structure and function and the blockade of apoptosis in intestinal epithelial cells; and regulation of the gut–brain axis through the production of neurotransmitters and vagus nerve function [6,7,8] (Figure 1) It is well-known that commensal microorganisms produce variable factors to foster an optimal adaptation to new niches in the host and to directly drive their physiological responses. The health-promoting influence of probiotics and probiotic-derived functional factors in intestinal diseases, including inflammatory bowel disease (IBD), colonic cancer and necrotizing enterocolitis, is discussed to support future studies on therapeutic applications of probiotics
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