Microbial Metabolites Determine Host Health and the Status of Some Diseases

Abstract

The gastrointestinal (GI) tract is a highly complex organ composed of the intestinal epithelium layer, intestinal microbiota, and local immune system. Intestinal microbiota residing in the GI tract engages in a mutualistic relationship with the host. Different sections of the GI tract contain distinct proportions of the intestinal microbiota, resulting in the presence of unique bacterial products in each GI section. The intestinal microbiota converts ingested nutrients into metabolites that target either the intestinal microbiota population or host cells. Metabolites act as messengers of information between the intestinal microbiota and host cells. The intestinal microbiota composition and resulting metabolites thus impact host development, health, and pathogenesis. Many recent studies have focused on modulation of the gut microbiota and their metabolites to improve host health and prevent or treat diseases. In this review, we focus on the production of microbial metabolites, their biological impact on the intestinal microbiota composition and host cells, and the effect of microbial metabolites that contribute to improvements in inflammatory bowel diseases and metabolic diseases. Understanding the role of microbial metabolites in protection against disease might offer an intriguing approach to regulate disease.

Keywords: immune cell; inflammatory bowel disease; intestinal epithelial cell; intestinal microbiota; metabolic disease; metabolite.

Figure 1

Conversion of dietary components and host-derived molecules to metabolites and their effect on microbial clades. Abbreviations: SCFAs, short-chain fatty acids; AHR, aryl hydrocarbon receptor.

Figure 2

Dietary fiber-derived short-chain fatty acids (SCFAs) affect intestinal epithelial cells (IECs) and immune cells. SCFAs derived from dietary fiber impact IECs through various mechanisms. These effects include enhancing barrier functions, maintaining intestinal barrier integrity, inducing IEC migration and wound healing, promoting proliferation, turnover, and inflammatory responses, and inducing antimicrobial peptide production and the assembly of tight junction proteins. In addition, SCFAs affect immune cells, including T cells, antigen-presenting cells, and others such as monocytes and macrophages. SCFAs induce the differentiation and tissue homing of regulatory T cells (Tregs), promote the cell proliferation and differentiation of helper T (Th) cells, modulate the function of antigen-presenting cells, and alter other immune cell properties. Abbreviations: NLRP3, NOD-like receptor pyrin domain-containing protein 3; HDAC, histone deacetylase; PAK1, p21 activated kinase; MFGE8, milk fat globule-EGF factor 8; GPR, G-protein coupled receptor; MAPK, mitogen-activated protein kinase; Treg, regulatory T cell; Th, helper T cell; DCs, dendritic cells.