Figure 3. Post-FMT interaction of miRNAs and glycans with the immune system and the gut microbiota.

C. difficile-derived TcdB can reduce the expression of miR-150, miR-26b, miR-23a, and miR-28-5p, which downregulate the expression levels of IL-18, FGF-21, IL-12B, and TNFRSF9 inflammatory gene targets, respectively. IL-12B suppression by miR23a prevents the proliferation of Th1 cell. Likewise, the overexpression of miR-28-5p prevents TNFRSF9 production and subsequently reduces NK cell activation and inflammatory cytokine secretion. TcdB further inhibits the activity of intestinal ion transporter NHE3 and Cl⁻/HCO₃⁻ exchanger protein DRA. TcdB, along with TcdA, can induce vascular permeability and thereby increase the accumulation of VEGF-A and probably the activation of the VEGFR-2. The elevated presence of glycans, in return, accelerates the growth of Bacteroides and Bifidobacteria genera. Bacteroides fragilis can reduce the proportion of N-linked glycans. Prevotella strains decrease the Bacilli/Clostridia ratio, suppress the expression of AFAP1, and catabolize PLP to attenuate inflammation. AFAP1, actin filament-associated protein 1; DRA, down-regulated in adenoma; FGF-21, fibroblast growth factor 21; NHE3, Na+/H+ exchanger 3; NK, natural killer; PLP, pyridoxal-5-phosphate; TcdA, toxin A; TcdB, toxin B; Th 1, T helper 1; TNFRSF9, TNF receptor superfamily member 9; VEGF-A, vascular endothelial growth factor A; VEGFR-2, VEGF-A receptor.