Nonpharmacological Treatment Strategies for the Management of Canine Chronic Inflammatory Enteropathy-A Narrative Review

Abstract

Chronic inflammatory enteropathy (CIE) refers to a heterogeneous group of idiopathic diseases of the dog characterised by persistent gastrointestinal (GI) clinical signs. If conventional dietary treatment alone would be unsuccessful, management of CIE is traditionally attained by the use of pharmaceuticals, such as antibiotics and immunosuppressive drugs. While being rather effective, however, these drugs are endowed with side effects, which may impact negatively on the animal's quality of life. Therefore, novel, safe and effective therapies for CIE are highly sought after. As gut microbiota imbalances are often associated with GI disorders, a compelling rationale exists for the use of nonpharmacological methods of microbial manipulation in CIE, such as faecal microbiota transplantation and administration of pre-, pro-, syn- and postbiotics. In addition to providing direct health benefits to the host via a gentle modulation of the intestinal microbiota composition and function, these treatments may also possess immunomodulatory and epithelial barrier-enhancing actions. Likewise, intestinal barrier integrity, along with mucosal inflammation, are deemed to be two chief therapeutic targets of mesenchymal stem cells and selected vegetable-derived bioactive compounds. Although pioneering studies have revealed encouraging findings regarding the use of novel treatment agents in CIE, a larger body of research is needed to address fully their mode of action, efficacy and safety.

Keywords: canine chronic inflammatory enteropathy; clinical nutrition; faecal microbiota transplantation; phytochemical; postbiotic; prebiotic; probiotic; stem cell therapy; synbiotic.

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).