Enterocolic increase of cannabinoid receptor type 1 and type 2 and clinical improvement after probiotic administration in dogs with chronic signs of colonic dysmotility without mucosal inflammatory changes

Abstract

BackgroundColonic dysmotility in dogs can cause different GI signs. Sometimes, histology of enterocolic biopsies does not reveal inflammatory infiltrates or mucosal lesions that are typically associated with clinical disease activity. It is speculated that, similarly to humans, colonic dysmotility may be anxiety‐based, although recent data demonstrate that irritable bowel syndrome (IBS) could result from acute infectious enteritis. Specific Lactobacillus spp. strains administered orally in humans induced the expression of μ‐opioid and cannabinoid receptors in mucosal enterocytes, modulating intestinal morphine‐like analgesic functions. We investigated the potential association of GI signs caused by colonic dysmotility and mucosal expression of cannabinoid receptors in intestinal epithelial cells and the number of mucosal mast cells.MethodsTen to 15 endoscopic biopsies were collected from colonic mucosa of 20 dogs diagnosed with dysmotility disturbances before and after probiotic (Slab51 bacterial blend; Sivoy®) administration (3‐month period). Number and distribution of mast cells (MCs), and cannabinoid receptor type 1 (CB1) and type 2 (CB2) were evaluated by immunohistochemistry and PCR. Results were compared to data obtained from five clinically healthy dogs (archive samples).Key resultsDecreased numbers of MCs (P < .0001) and increased CB1‐ and CB2‐positive epithelial cells (P < .0001) in diseased dogs were positively associated with post‐treatment CCECAI scores (P < .0001).Conclusions and inferencesOur results suggest that probiotic administration can reduce signs of colonic dysmotility, possibly due to microbiota modulation and epithelial cell receptor–mediated signaling in intestinal mucosa.

Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice

“…A number of genetically unmodified bacteria have shown potential anti-inflammatory properties in mice and, more recently, it has been proven that these effects are at least partially mediated by the endocannabinoid system. In a paper by Rossi et al, indeed, the widely used probiotic VSL#3 was able to modulate several genes encoding for enzymes involved in endocannabinoid (EC) metabolism and to relatively modulate the expression of CB1 and CB2 at the intestinal surface [31]. A clear advantage of using engineered pNAPE-LP rather than wild-type probiotics is the possibility of selecting carrier bacteria that can increase the likelihood of reaching therapeutic doses of the appropriate compound and selectively modulating the endocannabinoid system.…”

Circulating Endocannabinoids as Diagnostic Markers of Canine Chronic Enteropathies: A Pilot Study

“…The expression of CB1 was documented in lamina propria and epithelial cells, and that of CB2 in lamina propria, mast cells, immunocytes, blood vessels, and smooth muscle cells of dogs ( 14 ). In addition, dogs suffering from chronic idiopathic large bowel diarrhea exhibited decreased expression of both CB1 and CB2 receptors in colonic mucosa when, compared with dogs in the control group ( 24 ). Against this background, the aims of this investigation were to determine plasmatic levels of AEA, 2-AG, PEA and OEA in healthy dogs and to evaluate their usefulness as biomarkers of CE in dogs, as well as their diagnostic ability in distinguish among the different forms of CE.…”

The Peripheral Cannabinoid Receptor Type 1 (CB1) as a Molecular Target for Modulating Body Weight in Man

“…Microbiome CB 1 receptor antagonism [49] or THC [50] increases Akkermansia muciniphila. Probiotic treatment increases CB 1 and/or CB 2 expression [51,52].…”