Figure 1.

Schematic representation of the potential mechanisms underpinning beneficial effects of the main nonpharmacological treatment strategies in chronic inflammatory enteropathy of dogs (CIE). (A) Pre-, pro- and synbiotics: Probiotic microorganisms compete with pathogenic bacteria for adhesion sites at the level of the mucus layer or onto enterocytes (1); ferment prebiotic fibre with consequent production of postbiotics (e.g., short-chain fatty acids) (2); compete for growth substrates and produce and release essential dietary nutrients (e.g., vitamins) (3); inhibit the expansion of pathogenic microorganisms via the production of antimicrobial peptides (5); promote, together with prebiotic fibre compounds, tight-junction protein expression and strengthening of gut barrier function (6); and modulate immune responses by expanding the population of regulatory T cells (T-regs) and enhancing secretory immunoglobulin-A production (7). Additional direct mechanisms of action of prebiotics encompass blockage of pathogen adhesion by serving as ligand analogues (4) and immunoregulatory effect, exerted via the differential activation of inflammation-related receptors (8). (B) Phyto- and phycochemicals: curcumin is endowed with antibacterial activity against deleterious microbes (1) and functions as a potent anti-inflammatory compound by inhibiting nuclear factor-κB (NF-κB) (2); palmitoylethanolamide (PEA) quenches phlogistic reactions through the activation of cannabinoid (CB) receptors and peroxisome proliferator-activated receptor (PPAR)-α (3); fucoidan hinders inflammatory cell egression from blood vessels via P- and L-selectin blockade (4), upregulates tight-junction protein claudin-1 expression (5) and is a source of fermentable fibre (6). (C) Faecal microbiota transplant: stool transplant reinstates gut homeostasis through a direct interaction between donor and recipient intestinal microbiota (1), restores normal faecal bile acid metabolism (2) and exerts immunoregulatory effects (3). (D) Stem cells: mesenchymal stromal cells suppress the activity of different immune cells (1), transdifferentiate into enterocytes (2), hamper fibrosis (3) and intestinal epithelial cell apoptosis (4) and induce T-reg differentiation and expansion (5).