Inflammatory bowel disease in dogs: An overview

Introduction

Inflammatory bowel disease (IBD) is a persistent and recurring condition affecting the gastrointestinal tract, distinguished by mucosal inflammation, notable for recurring instances of diarrhoea and vomiting and considered as the most common cause of chronic intestinal disease in dogs. Inflammatory bowel disease is also referred to as idiopathic, as it lacks a known underlying cause for intestinal inflammation. The various types of IBD in dogs primarily vary based on the types of cells found in the intestinal mucosa, including lymphocytes, plasma cells, eosinophils, macrophages, neutrophils or combinations of these cells. The pathogenesis of IBD involves a multifaceted interplay of genetic predisposition, environmental influences, immune response and dietary elements. An imbalance within the intestinal microbiota is identified as a major contributing factor in the development of IBD in dogs through the breakdown of immune tolerance to bacterial antigens within the intestinal lumen. This breakdown occurs due to disruption in the mucosal barrier, dysregulation of gutassociated lymphoid tissue, disturbance in the microbial flora or a combination of these factors. The development of early, non-invasive diagnostic methods, such as the use of various inflammatory biomarkers, plays an important role in the diagnosis of IBD. Among serum biomarkers, the detection of perinuclear antineutrophilic cytoplasmic antibodies (pANCAs) in dogs can be used as a helpful diagnostic tool to differentiate between dogs with IBD and those with other chronic gastrointestinal conditions. These are autoantibodies surrounding the granulocyte nucleus with a staining pattern and the primary target of these antibodies is myeloperoxidase, although they also attack other antigens like lactoferrin and elastase. Also, the evaluation of the expression of microRNAs (miRs) in the serum and colon tissue will offer a potential link between genetic susceptibility, environmental and immunological factors involved in the pathogenesis of IBD and may serve as a clinically useful biomarker for the diagnosis and treatment of canine IBD. Inflammatory bowel disease comprises a group of chronic intestinal disorders characterized by infiltration of inflammatory cells into the intestinal mucosal lamina propria (Nelson et al., 1988) [53] . In dogs, with chronic inflammatory enteropathies, approximately 50-66% exhibit [73, 48, 45, 38, 18, 71, 35, 23, 11, 8, 21, 25, 7, 33, 30, 36, 68] . Radiography is commonly employed in the evaluation of dogs with gastrointestinal disease and may reveal intestinal wall thickening, irregular mucosal patterns, gas accumulation or in severe cases, barium contrast abnormalities such as thumb-printing, although contrast studies are preferred for accurate assessment of bowel wall thickness (Raji, 2010; Allenspach, 2013; Hotel and Tams, 2016; Stieger-Vanegas, 2020). Additionally, radiographic examination is valuable in excluding differential diagnoses such as foreign bodies, neoplasia and structural gastrointestinal abnormalities that may mimic IBD (El-Zahar et al., 2021). Ultrasonography is a valuable non-invasive imaging modality in the evaluation of canine IBD, allowing assessment of intestinal wall thickness, layering, echogenicity, motility and regional lymph nodes (Linta et al., 2021). A normal intestinal wall consists of distinct echogenic and hypoechoic layers, whereas inflammatory lesions may present with diffuse wall thickening, altered echogenicity and enlargement of intestinal layers, with intestinal wall thickening being considered one of the most important ultrasonographic indicators of inflammation (Spohr et al., 1995). Administration of polyethylene glycol before ultrasonography improves intestinal distension and wall visualization, providing diagnostic efficacy comparable to contrast radiography for detecting intestinal lesions (Parente et al., 2004). Ultrasonography is superior to radiography for evaluating intestinal wall thickness, mesenteric lymphadenopathy and the distribution of intestinal lesions, while also helping to exclude conditions such as intussusception, foreign bodies, obstructions, fungal lesions, localized tumours and other causes of chronic gastrointestinal disease (Ruaux et al., 2005;Bhavani et al., 2021). However, ultrasonographic findings are not specific for IBD, as alterations in wall thickness, echogenicity and layering may occur in other intestinal disorders, particularly neoplasia, where abnormal wall layering is more frequently observed (Wdowiak et al., 2014). Furthermore, some dogs with IBD may show normal ultrasonographic findings, and intestinal wall thickness alone lacks sufficient sensitivity and specificity for definitive diagnosis (Collins-Webb et al., 2023). Nevertheless, ultrasonography remains an important diagnostic tool for differentiating inflammatory from neoplastic intestinal disease and guiding clinical management (Bhavani et al., 2023) [35, 21, 46, 66, 55, 60, 10, 71, 16, 9, 39, 65, 43] . Colonoscopy and histopathology are important diagnostic tools for canine IBD. Endoscopic findings commonly include mucosal erythema, friability, increased granularity, erosions, ulcerations, white speckling and stenosis, reflecting varying degrees of intestinal mucosal inflammation (Jergens et al., 2010b). Colonoscopy is m ore sensitive than ultrasonography for diagnosing colitis and assists in identifying the affected intestinal segments, assessing inflammatory activity and differentiating IBD from other causes of chronic enteropathy, although it has limited ability to evaluate deeper intestinal layers and colonic function (Bhavani et al., 2023). Endoscopic lesions may be quantitatively assessed using scoring systems based on granularity, friability and erosions (Slovak et al., 2015). Histopathological examination remains the gold standard for confirming IBD and typically reveals mucosal inflammation with villous blunting, epithelial injury, crypt hyperplasia or dilation, lacteal dilation, mucosal fibrosis and disruption of mucosal architecture (Kleinschmidt et al., 2006). The inflammatory infiltrate is predominantly composed of lymphocytes and plasma cells, with occasional eosinophils, neutrophils and macrophages, supporting the classification of lymphocytic-plasmacytic enteritis as the most common histological form of canine IBD (Bhavani et al., 2023). Histological severity is graded based on both inflammatory and morphological changes, ranging from mild to severe lesions, and provides definitive evidence of intestinal inflammation, complementing clinical indices such as the CIBDAI in assessing disease severity and progression (Bhavani et al., 2023). Histopathological evaluation of endoscopic biopsy samples may additionally reveal epithelial degeneration, crypt epithelial hyperplasia and mononuclear cell infiltration in the lamina propria, particularly in lymphocytic-plasmacytic colitis (Priya et al., 2023). The diagnosis of canine IBD can also be supported by noninvasive diagnostic methods, particularly the assessment of inflammatory biomarkers such as perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and microRNAs. Perinuclear antineutrophil cytoplasmic antibodies have been investigated as useful biomarkers in canine inflammatory bowel disease, with reported positivity ranging from 23% to 51% of affected dogs, indicating moderate diagnostic sensitivity (Allenspach et al., 2004;Luckschander et al., 2006). pANCA testing assists in differentiating IBD from other gastrointestinal disorders with similar clinical manifestations and provides evidence supporting an autoimmune component in disease pathogenesis. These autoantibodies, typically detected by indirect fluorescent antibody testing (IFAT), produce a characteristic perinuclear staining pattern and primarily target myeloperoxidase, although reactivity against other neutrophil antigens such as lactoferrin, elastase and pathogen-associated molecular patterns has also been reported (Weiner and Segelmark, 2016). In dogs with IBD, increased pANCA concentrations are believed to reflect ongoing intestinal inflammation and immune dysregulation, potentially triggered by dysbiosis and microbial antigens. Furthermore, serial measurement of pANCA levels may aid in monitoring disease progression and therapeutic response, with declining titres indicating clinical improvement and increasing levels suggesting disease exacerbation (Chen et al., 2020). MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression posttranscriptionally and play important roles in cellular proliferation, differentiation, immune regulation and disease pathogenesis (O'Brien et al., 2018). Owing to their stability in exosomes, microvesicles, lipoproteins and RNA-protein complexes, miRs can be detected in tissues and a wide range of biological fluids including serum, plasma, urine, saliva and faeces, making them attractive diagnostic and prognostic biomarkers (Varvil and Dos Santos, 2023). Their expression is commonly quantified using reverse transcription real-time PCR, with approaches such as the S-Poly (T) primer method providing improved sensitivity and specificity and U6 small nuclear RNA frequently used as an endogenous reference gene (Konstantinidis et al., 2020). Altered miR expression has been associated with inflammatory, autoimmune and other pathological conditions, including canine IBD. In dogs with IBD, significant upregulation of miR-16, miR-21, miR-122 and miR-147, along with downregulation of miR-185, miR-192 and miR-223, has been reported in colonic mucosa compared with healthy controls (Konstantinidis et al., 2020). Increased expression of miR-16 and miR-147 has also been demonstrated in the colonic mucosa and serum of dogs with large intestinal IBD, suggesting their potential utility as noninvasive biomarkers for disease diagnosis and monitoring (Stiegeler et al., 2021) [58, 4, 47, 72, 14, 54, 69, 44, 67] . The primary goals of canine inflammatory bowel disease treatment are to correct nutritional deficiencies, reduce intestinal inflammation, control dysbiosis and eliminate potential antigenic stimuli from the diet and intestinal microbiota (Marchesi et al., 2017). Dietary management forms the cornerstone of therapy, with hydrolysed protein or novel-protein diets proving effective, particularly in mild cases (Mandigers et al., 2010). Dogs with moderate to severe IBD are commonly treated with a combination of dietary modification, prednisolone and metronidazole, whereas mild cases may respond to dietary therapy alone (Mandigers et al., 2010).

Corticosteroids remain the principal immunosuppressive agents, with prednisolone administered initially at immunosuppressive doses and gradually tapered to maintenance levels; additional agents such as azathioprine or chlorambucil may be used in refractory cases. Antibiotics, particularly metronidazole, may provide both antimicrobial and anti-inflammatory benefits, while prebiotics and probiotics can aid in modulating intestinal microflora (Marchesi et al., 2017). Assessment of serum cobalamin and folate concentrations is recommended, and supplementation should be provided when deficiencies are identified, especially in dogs with chronic gastrointestinal disease (Kather et al., 2020). In cases of large bowel inflammation, sulfasalazine may be employed as a therapeutic option because its active metabolite, mesalamine, is activated by colonic bacteria (Walker and McMahon, 2021). Treatment duration varies according to disease severity, and although long-term remission can often be achieved, complete cure is uncommon (Marchesi et al., 2017). Dietary management is a fundamental component of canine inflammatory bowel disease therapy and is often the first-line treatment, particularly in mild cases (Gaschen and Merchant, 2011). An ideal diet for dogs with IBD should be nutritionally balanced, highly palatable and digestible, containing a novel intact or hydrolysed protein source, digestible carbohydrates, and low levels of gluten, lactose and fat. Novel-protein diets utilize a single protein source not previously consumed by the dog, whereas hydrolysed-protein diets contain proteins enzymatically broken down into small peptides that are less likely to trigger immune responses (Collier et al., 2022). Dietary trials should be conducted exclusively for 8-12 weeks without introducing other food items to accurately assess response (Gaschen and Merchant, 2011). Mild cases of IBD may achieve remission through dietary management alone, whereas moderate to severe cases often require a combination of dietary modification and pharmacological therapy (Marchesi et al., 2017). Evidence suggests that combining dietary intervention with medical treatment reduces disease relapse rates more effectively than pharmacotherapy alone, with hydrolysed-protein diets showing greater efficacy than novel-protein diets in preventing recurrence (Ambrosini et al., 2020). Common novel protein sources used in hypoallergenic diets include white fish, venison, rabbit, duck, salmon, catfish and lamb (Collier et al., 2022) [51, 50, 41, 70, 27, 15, 6] .

Conclusion

Canine inflammatory bowel disease is a chronic, multifactorial enteropathy resulting from complex interactions among genetic predisposition, immune dysregulation, intestinal microbiota, dietary factors and environmental influences. The disease is characterized by persistent gastrointestinal signs and requires a systematic diagnostic approach involving clinical assessment, laboratory investigations, imaging, endoscopy and histopathology. Although histopathological examination remains the gold standard for diagnosis, emerging non-invasive biomarkers such as pANCA and microRNAs show promise for improving early detection and disease monitoring. Effective management relies on individualized dietary modification, immunosuppressive therapy, control of dysbiosis and longterm monitoring to achieve sustained clinical remission and improve quality of life.

References

1. Allenspach, K. 2011. Clinical immunology and immunopathology of the canine and feline intestine. Vet. Clin. Small Anim. Pract. 41: 345-360.
2. Allenspach, K. and Mochel, J.P. 2020. Genetics and Immunopathogenesis of Chronic Inflammatory Enteropathies in Dogs. Adv. Small Anim. Care. 1: 91100.
3. Allenspach, K., Culverwell, C. and Chan, D. 2016. Long-term outcome in dogs with chronic enteropathies: 203 cases. Vet. Rec. 178: 368-371.
4. Allenspach, K., Luckschander, N., Styner, M., Seibold, F., Doherr, M., Aeschbach, D. and Gaschen, F. 2004. Evaluation of assays for perinuclear antineutrophilic cytoplasmic antibodies and antibodies to Saccharomyces cerevisiae in dogs with inflammatory bowel disease. Am. J. Vet. Res. 65: 1279-1283.
5. Allenspach, K., Wieland, B., Grone, A. and Gaschen, F. 2007. Chronic enteropathies in dogs: evaluation of risk factors for negative outcome. J. Vet. Intern. Med. 21: 700-708.
6. Ambrosini, Y.M., Neuber, S., Borcherding, D., Seo, Y.J., Segarra, S., Glanemann, B., Garden, O.A., Müller, U., Adam, M.G., Dang, V. and Borts, D. 2020. Treatment with hydrolyzed diet supplemented with prebiotics and glycosaminoglycans alters lipid metabolism in canine inflammatory bowel disease. Front. Vet. Sci. 7: p.451.
7. Benvenuti, E., Bottero, E., Pierini, A., Gori, E. and Marchetti, V. 2020. The swab sampled dry fecal cytology in healthy dogs and in dogs with acute and chronic diarrhea: a pilot study. Jpn. J. Vet. Res. 68: 151158.
8. Bhargavi, M., Shobhamani, K., Kumari, N. and Srilatha, C. 2017. Diagnostic aspects and haemato-biochemical changes associated with canine parvoviral enteritis in dogs. Int. J. Curr. Microbiol. App. Sci. 6: 3357 3364.
9. Bhavani, M.S., Kavitha, S., Nagarajan, B., Pazhanivel, N., Vairamuthu, S. and Bhat, A.A. 2023. An endoscopic and histopathological assessment and correlation of endoscopic score with clinical activity index (CIBDAI) in the diagnosis of canine idiopathic inflammatory bowel disease. Iran. J. Vet. Res. 24: 58-64.
10. Bhavani, M.S., Kavitha, S., Sumathi, D. and Bhat, A.A. 2021. Abdominal ultrasonography in canine inflammatory bowel disease: A short study. J. Entomol. Zool. Stud. 9: 1977-1981.
11. Cabral, V. L., De Carvalho, L. and Miszputen, S. J. 2001. Importance of serum albumin values in nutritional assessment and inflammatory activity in patients with Crohn's disease. Arq. Gastroenterol. 38: 104-108.
12. Calalang, J., Cheung, H., Lichimo, K. and So, B. 2021. Identifying breed, dietary, and reproductive factors affecting the gut microbiome of dogs with inflammatory bowel disease. UJEMI. 26: 1-13.
13. Cerquetella, M., Spaterna, A., Laus, F., Tesei, B., Rossi, G., Antonelli, E., Villanacci, V. and Bassotti, G. 2010. Inflammatory bowel disease in the dog: differences and similarities with humans. World J. Gastroenterol. 16: 1050-1056.
14. Chen, P., Zhou, G., Lin, J., Li, L., Zeng, Z., Chen, M. and Zhang, S. 2020. Serum biomarkers for inflammatory bowel disease. Front. Med. 7: p.123.
15. Collier, A.J., Gomez, D.E., Monteith, G., Plattner, B.L., Verbrugghe, A., Webb, J., Weese, J.S. and Blois, S.L. 2022. Investigating fecal microbial transplant as a novel therapy in dogs with inflammatory bowel disease: A preliminary study. Plos one. 17: e0276295.
16. Collins-Webb, A.G., Chong, D.L. and Cooley, S.D. 2023. Ultrasonographic intestinal muscularis thickening in dogs with histologically confirmed inflammatory bowel disease: 13 cases (2010-2021). Vet. Radiol. Ultrasound. 64: 345-350.
17. Craven, M., Dogan, B., Schukken, A., Volkman, M., Chandler, A., McDonough, P.L. and Simpson, K.W. 2010. Antimicrobial resistance impacts clinical outcome of granulomatous colitis in boxer dogs. J. Vet. Intern. Med. 24: 819-824.
18. Craven, M., Simpson, J.W., Ridyard, A.E. and Chandler, M.L. 2004. Canine inflammatory bowel disease: retrospective analysis of diagnosis and outcome in 80 cases (1995-2002). J. Small Anim. Pract. 45: 336 342.
19. Dandrieux, J.R. 2016. Inflammatory bowel disease versus chronic enteropathy in dogs: are they one and the same?. J. Small Anim. Pract. 57: 589-599.
20. DeGruttola, A.K., Low, D., Mizoguchi, A. and Mizoguchi, E. 2016. Current understanding of dysbiosis in disease in human and animal models. Inflamm. Bowel Dis. 22: 1137-1150.
21. El-Zahar, H., El-Rahman, A. and El-Naggar, A. 2021. Ultrasound, hematological and biochemical analysis in canine with inflammatory bowel disease. Zagazig Vet. J. 49: 471-481.
22. El-Zahar, H., El-Rahman, A. and El-Naggar, A. 2021. Ultrasound, hematological and biochemical analysis in canine with inflammatory bowel disease. Zagazig Vet. J. 49: 471-481.
23. Feldman, B.F., Zinkl, J.G., Jain, N.C. and Schalm, O.W. 2000. Schalm's Veterinary Hematology. (5th Ed.). Lippincott Williams and Wilkins, 1221p.
24. Felix, A.P., Souza, C.M.M. and de Oliveira, S.G. 2022. Biomarkers of gastrointestinal functionality in dogs: A systematic review and meta analysis. Anim. Feed Sci. Technol. 283: p.115183.
25. Frezoulis, P.S., Angelidou, E., Diakou, A., Rallis, T.S. and Mylonakis, M.E. 2017. Optimization of fecal cytology in the dog: comparison of three sampling methods. J. Vet. Diagn. Invest. 29: 767-771.
26. Garraway, K., Allenspach, K. and Jergens, A. 2018. Inflammatory bowel disease in dogs and cats. Today's Vet. Pract. 8: 29-38.
27. Gaschen, F.P. and Merchant, S.R. 2011. Adverse food reactions in dogs and cats. Vet. Clin. Small Anim. Pract. 41: 361-379.
28. German, A.J., Hall, E.J. and Day, M.J. 2003. Chronic intestinal inflammation and intestinal disease in dogs. J. Vet. Internal Med. 17: 8-20.
29. German, A.J., Hall, E.J. and Day, M.J. 2003. Chronic intestinal inflammation and intestinal disease in dogs. J. Vet. Internal Med. 17: 8-20.
30. Glanemann, B., Seo, Y.J., Priestnall, S.L., Garden, O.A., Kilburn, L., Rossoni Serao, M., Segarra, S., Mochel, J.P. and Allenspach, K. 2021. Clinical efficacy of prebiotics and glycosaminoglycans versus placebo in dogs with food responsive enteropathy receiving a hydrolyzed diet: A pilot study. Plos one. 16: p.e0250681.
31. Glas, J., Seiderer, J., Tillack, C., Pfennig, S., Beigel, F., Jurgens, M., Olszak, T., Laubender, R.P., Weidinger, M., Müller-Myhsok, B. and Goke, B. 2010. The NOD2 single nucleotide polymorphisms rs2066843 and rs2076756 are novel and common Crohn's disease susceptibility gene variants. PloS one. 5: p.e14466.
32. Hall, E.J. and Batt, R.M. 1992. Dietary modulation of gluten sensitivity in a naturally occurring enteropathy of Irish setter dogs. Gut. 33: 198 205.
33. Heilmann, R.M., Berghoff, N., Mansell, J., Grutzner, N., Parnell, N.K., Gurtner, C., Suchodolski, J.S. and Steiner, J.M. 2018. Association of fecal calprotectin concentrations with disease severity, response to treatment, and other biomarkers in dogs with chronic inflammatory enteropathies. J. Vet. Intern. Med. 32: 679692.
34. Hemida, M., Vuori, K.A., Moore, R., Anturaniemi, J. and Hielm-Bjorkman, A. 2021. Early life modifiable exposures and their association with owner reported inflammatory bowel disease symptoms in adult dogs. Front. Vet. Sci. 8: 14p.
35. Hotel, B.H. and Tams, T.R. 2016. Updates in clinical gastroenterology of dogs and cats. Vermont Veterinary Medical Association, Winter meeting, 13th February, 2012, Burlington Hilton Hotel, 74p.
36. Hung, M., Heinz, J., Steiner, J.M., Suchodolski, J. and Lidbury, J. 2023. Serum cobalamin and methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or other acute enteropathies. J. Vet. Intern. Med. 37: 1368-1375.
37. Jergens, A.E. 2020. Diagnosis and management of gastrointestinal motility disorders: GI motility disorders are a diagnostic and therapeutic challenge for many practitioners. Here's how to narrow down the affected area so you can identify the cause and provide appropriate treatment. VETTED. 115: 17-20.
38. Jergens, A.E. and Simpson, K.W. 2012. Inflammatory bowel disease in veterinary medicine. Front. Biosci. 4: 1404-1419.
39. Jergens, A.E., Schreiner, C.A., Frank, D.E., Niyo, Y., Ahrens, F.E., Eckersall, P.D., Benson, T.J. and Evans, R. 2003. A scoring index for disease activity in canine inflammatory bowel disease. J. Vet. Intern. Med. 17: 291 297.
40. Kather, S., Grutzner, N., Kook, P.H., Dengler, F. and Heilmann, R.M. 2020. Review of cobalamin status and disorders of cobalamin metabolism in dogs. J. Vet. Intern. Med. 34: 13-28.
41. Kleinschmidt, S., Meneses, F., Nolte, I. and HewickerTrautwein, M. 2006. Retrospective study on the diagnostic value of full-thickness biopsies from the stomach and intestines of dogs with chronic gastrointestinal disease symptoms. Vet. Pathol. 43: 1000-1003.
42. Konstantinidis, A.Ο., Pardali, D., Adamama-Moraitou, K.K., Gazouli, M., Dovas, C.I., Legaki, E., Brellou, G.D., Savvas, I., Jergens, A.E., Rallis, T.S. and Allenspach, K. 2020. Colonic mucosal and serum expression of microRNAs in canine large intestinal inflammatory bowel disease. BMC Vet. Res. 16: 1-14.
43. Lee, J.H., Kim, H.S., Lee, D., Yun, T., Koo, Y., Chae, Y., Kang, J.H., Kang, B.T., Yang, M.P. and Kim, H. 2021. Clinical signs, duodenal histopathological grades, and serum high-mobility group box 1 concentrations in dogs with inflammatory bowel disease. J. Vet. Intern. Med. 35: 2205-2214.
44. Linta, N., Pey, P., Baron Toaldo, M., Pietra, M., Felici, M., Bettini, G., Cipone, M. and Diana, A. 2021. Contrast-enhanced ultrasonography in dogs with inflammatory bowel disease. J. Vet. Intern. Med. 35: 2167 2176.
45. Luckschander, N., Allenspach, K., Hall, J., Seibold, F., Grone, A., Doherr, M.G. and Gaschen, F. 2006. Perinuclear antineutrophilic cytoplasmic antibody and response to treatment in diarrheic dogs with food responsive disease or inflammatory bowel disease. J. Vet. Intern. Med. 20: 221 227.
46. Maeda, S., Ohno, K., Uchida, K., Nakashima, K., Fukushima, K., Tsukamoto, A., Nakajima, M., Fujino, Y. and Tsujimoto, H. 2013. Decreased immunoglobulin A concentrations in feces, duodenum, and peripheral blood mononuclear cells of dogs with inflammatory bowel disease. J. Vet. Intern. Med. 27: 47-55.
47. Malewska, K., Rychlik, A., Nieradka, R. and Kander, M. 2011. Treatment of inflammatory bowel disease (IBD) in dogs and cats. Polish J. Vet. Sci. 14: 165-171.
48. Mandigers, P.J.J., Biourge, V., Van Den Ingh, T.S.G.A.M., Ankringa, N. and German, A.J. 2010. A randomized, open-label, positively-controlled field trial of a hydrolyzed protein diet in dogs with chronic small bowel enteropathy. J. Vet. Intern. Med. 24: 1350-1357.
49. Marchesi, M.C., Timpano, C.C., Busechian, S., Pieramati, C. and Rueca, F. 2017. The role of diet in managing inflamatory bowel disease affected dogs: a retrospective cohort study on 76 cases. Vet. Ital. 53: 297302.
50. Martinez-Medina, M., Denizot, J., Dreux, N., Robin, F., Billard, E., Bonnet, R., Darfeuille-Michaud, A. and Barnich, N. 2014. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 63: 116-124.
51. Nelson, R.W., Stookey, L.J. and Kazacos, E. 1988. Nutritional management of idiopathic chronic colitis in the dog. J. Vet. Intern. Med. 2: 133-137.
52. O'Brien, J., Hayder, H., Zayed, Y. and Peng, C. 2018. Overview of microRNA biogenesis, mechanisms of actions, and circulation. Front. Endocrinol. 9: p.388354.
53. Parente, F., Greco, S., Molteni, M., Anderloni, A., Sampietro, G.M., Danelli, P.G., Bianco, R., Gallus, S. and Porro, G.B. 2004. Oral contrast enhanced bowel ultrasonography in the assessment of small intestine Crohn's disease. A prospective comparison with conventional ultrasound, x ray studies and ileocolonoscopy. Gut. 53: 1652-1657.
54. Parker, H.G., Kim, L.V., Sutter, N.B., Carlson, S., Lorentzen, T.D., Malek, T.B., Johnson, G.S., DeFrance, H.B., Ostrander, E.A. and Kruglyak, L. 2004. Genetic structure of the purebred domestic dog. Sci. 304: 11601164.
55. Peiravan, A., Bertolini, F., Rothschild, M.F., Simpson, K.W., Jergens, A.E., Allenspach, K. and Werling, D. 2018. Genome-wide association studies of inflammatory bowel disease in German shepherd dogs. PloS one. 13: p.e0200685.
56. Priya, S.V., Kumar, G.S. and Senthilvel, K. 2023. Colonoscopic Examination, Histopathological findings and medical management of Lymphocytic-Plasmacytic colitis in a Dog. Indian J. Vet. Sci. Biotechnol. 19: 108110.
57. Rousseau, M. 2005. Severe lymphocytic-plasmacytic and atrophic gastritis, as well as, predominantly eosinophilic, severe enteritis, in a 19-month-old Labrador retriever. Can. Vet. J. 46: 264-267.
58. Ruaux, C.G., Steiner, J.M. and Williams, D.A. 2005. Early biochemical and clinical responses to cobalamin supplementation in cats with signs of gastrointestinal disease and severe hypocobalaminemia. J. Vet. Intern. Med. 19: 155-160.
59. Rychlik, A., Nieradka, R., Kander, M., Depta, A., Nowicki, M. and Sarti, K. 2007. Usefulness of endoscopic examination for the diagnosis of inflammatory bowel disease in the dog. Pol. J. Vet. Sci. 10: 113-118.
60. Rychlik, A., Nieradka, R., Kander, M., Nowicki, M., Wdowiak, M. and Kolodziejska-Sawerska, A. 2012. A correlation between the Canine Inflammatory Bowel Disease Activity Index score and the histopathological evaluation of the small intestinal mucosa in canine inflammatory bowel disease. Pol. J. Vet. Sci. 15: 315321.
61. Sandborn, W.J. and Yednock, T.A. 2003. Novel approaches to treating inflammatory bowel disease: targeting alpha-4 integrin. J. Am. Gastroenterol. 98: 2372-2382.
62. Simpson, K.W. and Jergens, A.E. 2011. Pitfalls and progress in the diagnosis and management of canine inflammatory bowel disease. Vet. Clin. North Am. Small Anim. Pract. 41: 381 -398.
63. Slovak, J.E., Wang, C., Sun, Y., Otoni, C., Morrison, J., Deitz, K., LeVine, D. and Jergens, A.E. 2015. Development and validation of an endoscopic activity score for canine inflammatory bowel disease. Vet. J. 203: 290-295.
64. Spohr, A., Koch, J. and Jensen, A.L. 1995. Ultrasonographic findings in a basenji with immunoproliferative enteropathy. J. Small Anim. Pract. 36: 79 82.
65. Stiegeler, S., Mercurio, K., Iancu, M.A. and Corr, S.C. 2021. The impact of microRNAs during inflammatory bowel disease: effects on the mucus layer and intercellular permeability. Cells. 10: p.3358.
66. Ullal, T.V., Marks, S.L., Huebner, S.N., Taylor, S.L. and Shelley, C.D. 2023. Association of folate concentrations with clinical signs and laboratory markers of chronic enteropathy in dogs. J. Vet. Intern. Med. 37: 455-464.
67. Varvil, M.S. and Dos Santos, A.P. 2023. A review on microRNA detection and expression studies in dogs microRNA expression in dogs. Front. Vet. Sci. 10: p.1261085.
68. Walker, J. and McMahon, L. 2021. Investigating and treating chronic diarrhoea in dogs. Part 2: specific disorders of the small and large intestines. In Pract. 43: 484-498.
69. Wdowiak, M.I.C.H.A.L., Rychlik, A., Nieradka, R., Kander, M.A.L.G.O.R.Z.A.T.A., Nowicki, M., Szweda, M. And Depta, A. 2014. Diagnosis, tests and difficulties in canine and feline inflammatory bowel disease. Med. Weter. 70: 460-467.
70. Weiner, M. and Segelmark, M. 2016. The clinical presentation and therapy of diseases related to antineutrophil cytoplasmic antibodies (ANCA).
71. Willard, M.D., Jergens, A.E., Duncan, R.B., Leib, M.S., McCracken, M.D., DeNovo, R.C., Helman, R.G., Slater, M.R. and Harbison, J.L. 2002. Interobserver variation among histopathologic evaluations of intestinal tissues from dogs and cats. J. Am. Vet. Med. Assoc. 220: 11771182.
72. Xavier, R. J. and Podolsky, D. K. 2007. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 448: 427-434.
73. Yogeshpriya, S., Veeraselvam, M., Krishnakumar, S., Arulkumar, T., Jayalakshmi, K., Saravanan, M., Ranjithkumar, M., Sivakumar, M. and Selvaraj, P. 2017. Technical review on inflammatory bowel disease in dogs and cats. Int. J. Sci. Environ. Technol. 6: 1833-1842.