Gut microbiota-derived metabolites tune host homeostasis fate

Abstract

The gut microbiota, housing trillions of microorganisms within the gastrointestinal tract, has emerged as a critical regulator of host health and homeostasis. Through complex metabolic interactions, these microorganisms produce a diverse range of metabolites that substantially impact various physiological processes within the host. This review aims to delve into the intricate relationships of gut microbiota-derived metabolites and their influence on the host homeostasis. We will explore how these metabolites affect crucial aspects of host physiology, including metabolism, mucosal integrity, and communication among gut tissues. Moreover, we will spotlight the potential therapeutic applications of targeting these metabolites to restore and sustain host equilibrium. Understanding the intricate interplay between gut microbiota and their metabolites is crucial for developing innovative strategies to promote wellbeing and improve outcomes of chronic diseases.

Keywords: Gut barriers; Gut microbiota; Metabolites; Mucosal immunity.

Fig. 1

The process of maintaining the balance in the renewal and differentiation of intestinal epithelial cells. Lgr5⁺ stem cells reside adjacent to Paneth cells at the base of the crypt. These Lgr5⁺ stem cells constantly generate rapidly proliferating TA cells, filling the crypt. Subsequently, TA cells undergo differentiation into various functional cell types present within the villi, including enterocytes, tuft cells, goblet cells, and enteroendocrine cells. Lactic acid-producing bacteria, such as Bifidobacterium and Lactobacillus, contribute to the renewal of intestinal epithelial cells. The lactate produced by these symbiotic organisms is recognized by the GPR81 on Paneth and stromal cells, facilitating regeneration through the Wnt3/β-catenin pathway. The mucin-degrading bacterium A. muciniphila promotes intestinal stem cell-mediated epithelial regeneration using metabolites such as SCFA within the Wnt3/β-catenin pathway. Gut microbiota-derived tryptophan derivatives, along with SCFA, stimulate the expression of junctional proteins (such as occludin, claudins, and zonula occludens), thereby enhancing the gut barrier functions

Fig. 2

Cross-talk between gut microbiota-derived metabolites and various organs. Microbial byproducts, such as lactate, traverse through the bloodstream to reach the bone marrow, triggering stromal cells to release SCF and Cxcl2 influenced by GPR81 signaling. This interaction impacts bone marrow functions. Butyrate, generated by the gut microbiota, reinforces the gut barrier, fortifies the host against pathogen infiltration, and alleviates the effects of pancreatitis. Certain bacteria producing BSH elevate levels of deconjugated and secondary BAs within the colon. These BAs stimulate the production of Wnt2b in colonic mesenchymal stem cells through FXR activation, promoting increased cell growth in colonic crypts. Palmitic acid derived from Lactobacillus exhibits the ability to enhance the production of type-I IFN from pDC and monocytes. This increase in fatty acids contributes to the host's defense against influenza infection through the GPR40/120 mechanism