Cross Talk between Gut Microbiota and Intestinal Mucosal Immunity in the Development of Ulcerative Colitis

Abstract

Ulcerative colitis (UC), a nonspecific inflammatory disease, is characterized by inflammation and mucosal damage in the colon, and its prevalence in the world is increasing. Nevertheless, the exact pathogenesis of UC is still unclear. Accumulating data have suggested that its pathogenesis is multifactorial, involving genetic predisposition, environmental factors, microbial dysbiosis, and dysregulated immune responses. Generally, UC is aroused by inappropriate immune activation based on the interaction of host and intestinal microbiota. The relationship between microbiota and host immune system in the pathogenesis of UC is complicated. However, increasing evidence indicates that the shift of microbiota composition can substantially influence intestinal immunity. In this review, we primarily focus on the delicate balance between microbiota and gut mucosal immunity during UC progression.

Keywords: gut microbiota; mucosal immunity; ulcerative colitis.

FIG 1

Role of intestinal immune homeostasis on ulcerative colitis. Goblet cells and Paneth cells secret AMPs to defeat microbial encroachment. Mature dendritic cells promoted the maturation of B cells into IgA-secreting plasma cells and irritated the differentiation of naive T cells into functional populations of Th1, Th2, Th9, Th17, or Treg cells, thereby producing excessive cytokines. Similar to Th cells, ILCs could produce numerous cytokines that served as significant signals in the augmentation and perpetuation of UC. AMPs, antimicrobial peptides; IgA, immunoglobulin A; Th, T-helper-type; ILCs, innate lymphoid cells.

FIG 2

Cross talk of gut microbiota and intestinal mucosal immunity. SFB activated signal transducer and STAT3 to upregulate the expression of SAA, which induced the proliferation of Th17 cells and the production of IL-17. IFN-γ-expressing Th1 cells in mice were induced by K. pneumoniae in a TLR-dependent and IL-18-dependent manner. Colonization with the genus Clostridium could promote Treg cell accumulation by providing an environment rich in TGF-β. Aldh1a2-expressing DCs promoted by B. infantis could increase the quantity of RA and further upregulate the expression of Treg cells from naive T cells. Microbial metabolites, particularly SCFAs, vitamin D, secondary bile acids, and amino acids, could indirectly modify the resident and circulating immune cells. SFB, segmented filamentous bacteria; STAT, signal transducer and activator of transcription; SAA, serum amyloid A; RA, retinoic acid; SCFAs, short-chain fatty acids.