Role of gut microbiota in infectious and inflammatory diseases

Abstract

Thousands of microorganisms compose the human gut microbiota, fighting pathogens in infectious diseases and inhibiting or inducing inflammation in different immunological contexts. The gut microbiome is a dynamic and complex ecosystem that helps in the proliferation, growth, and differentiation of epithelial and immune cells to maintain intestinal homeostasis. Disorders that cause alteration of this microbiota lead to an imbalance in the host's immune regulation. Growing evidence supports that the gut microbial community is associated with the development and progression of different infectious and inflammatory diseases. Therefore, understanding the interaction between intestinal microbiota and the modulation of the host's immune system is fundamental to understanding the mechanisms involved in different pathologies, as well as for the search of new treatments. Here we review the main gut bacteria capable of impacting the immune response in different pathologies and we discuss the mechanisms by which this interaction between the immune system and the microbiota can alter disease outcomes.

Keywords: cytokines; gut microbiota; immune modulation; infectious diseases; inflammation; microbiome.

Figure 1

Main phyla and functions associated with the intestinal microbiota. Created with BioRender.com and coreldraw.com.

Figure 2

Bacteroides/Prevotella colonization and cytokine modulation. Bacteroides fragilis was associated with the induction of an anti-inflammatory response, inducing the differentiation of CD4+ T cells into Treg cells, which produce IL-10 and suppress Th17. This differentiation into Treg is mediated by TLR2 (from CD4+ cells), which recognizes polysaccharide A (from the bacterial outer membrane), activating a signaling cascade. Prevotella copri stimulates dendritic cells to express high levels of IL-6 and IL-23, which may increase the number of intestinal Th17 cells. P. histicola suppresses serum levels of pro-inflammatory cytokines such as IL-2, IL-17, and TNF-α, by increasing Treg cells in the gut and reducing Th17 cell responses. Created with Biorender.com.

Figure 3

Dysbiosis in inflammatory and infectious diseases. (A,B) Cytokines produced by intestinal intraepithelial lymphocytes (IEL) correlate with the relative abundance of some bacterial taxa in IBD. In the UC group, there was positive correlation between the abundances of Cynanobacteria, Christensenellaceae, and Pseudomonadaceae and IL-1β; between Cynanobacteria, Bacillales, and Verrucomicrobiaceae and IL-17A; between Peptococcaceae and TNF-α; and between Cynanobacteria, Desulfovibrionaceae, and Pseudomonadaceae and IFN-γ. In the CD group, there was positive correlation between the abundances of Victivallaceaea and Sphingomonadaceae and IL-1β; between Staphylococcaceaea and IL-17A; between Rikenellaceae and TNF-α; and between Staphylococcaceaea and Rikenellaceae and IFN-γ. (C) Culture with Collinsella reduces the expression of junction proteins, increasing intestinal permeability, and influences the secretion of IL-17A, CXCL1 and CXL5, which can trigger neutrophil recruitment and NFkb activation, possibly increasing pro-inflammatory conditions in RA. (D) Lupus activity was positively associated with the genera Streptococcus, Campylobacter and Veillonella, and negatively correlated with Bifidobacterium. Streptococcus combined with Veillonella enhance the TNF-α, IL-8, IL-6, and IL-10 response while Bifidobacterium is associated with improved gastrointestinal barrier function and suppression of pro-inflammatory cytokines. Together, these changes possibly induce an inflammatory state. Created with Biorender.com.