Objective: In the present study, we investigated the benefits of rectal enema probiotic combination in dogs with atopic dermatitis and detected circulating serum zonulin levels in these. Material and Methods: An open-label, self-controlled case series involved 6 privately owned dogs with atopic dermatitis. Diagnosis involved corneometric analytes, Canine Atopic Dermatitis Extent and Severity Index version 4 (CADESI-04) scores, visual analogue scale (VAS) pruritus scores and in vitro allergen specific tests. Faecal samples were forwarded to dual indexing one-step polymerase chain reaction and 16S rRNA targeted metagenomics in an attempt to determine gut microbiota alterations before and after rectal enema probiotic once daily for 10 days. Results: Following rectal enema probiotic treatment, as the in the vast majority Prevotella genus was significantly detected in association with clinical cure and recovery. Median CADESI-04 (p=0.028) and VAS pruritus scores (p=0.028) along with circulating zonulin (p=0.026) levels were decreased in atopic dermatitis cases on day 10 in contrast to 0th day values. Corneometric analysis involving median epidermal pH (p=0.027) and hydration values (p=0.028) revealed a significant improvement. Conclusion: This positive impact on skin inflammation and diminshed pruritus after application of rectal enema probiotic in this model of atopic dermatitis in dogs probably presented withdrawal of chronic barrier disruption and healed tigh junctions. The selected Lactobacillus probiotic strains used as an enema potentially regulate on skin health by the manipulation of the gut microbiome resulted with intestinal balance.
Keywords: Canine atopy; intestinal microbiome; probiotics; rectal enema; zonulin
Amaç: Bu çalışmada, atopik dermatitisli köpeklerde probiyotik kombinasyonlarının rektal uygulama yararlarının araştırılması ve bunlarda serum zonulin seviyelerinin belirlenmesi amaçlandı. Gereç ve Yöntemler: Açık-uçlu, öz deneyimli olgu serisi atopik dermatitisli 6 sahipli köpekten oluştu. Tanıda korneometrik analiz, Köpeklerde Atopik Dermatit Yaygınlık ve Şiddet İndeksi-04 [Canine Atopic Dermatitis Extent and Severity Index version 4 (CADESI-04)] skoru, vizüel analog skala (VAS) kaşıntı skoru ve in vitro alerjen spesifik test kullanıldı. Dışkı örnekleri, 10 gün boyunca günde 1 kez rektal enema probiyotik öncesi ve sonrasında bağırsak mikrobiyota değişikliklerini belirlemek amacıyla metagenomikleri hedefleyen ikili indeksleme tek adımlı polimeraz zincir reaksiyonu ve 16S rRNA analizine gönderildi. Bulgular: Rektal enema probiyotik sağaltımını takiben klinik iyileşme ve tedaviyle ilişkili büyük çoğunluğu Prevotella cinsi olacak şekilde önemli bulundu. Ortalama CADESI-04 (p=0,028) ve VAS kaşıntı skoru (p=0,028) ile zonulin (p=0,026) seviyesi 0. gün değerlerine kıyasla 10. günde azaldı. Korneometrik analizlerden epidermal pH (p=0,027) ve hidrasyon değeri (p=0,028) belirgin iyileşme gösterdi. Sonuç: Köpeklerde, bu atopik dermatitis modelinde rektal enema probiyotik uygulanmasından sonra deri yangısı ve azalan kaşıntı üzerindeki olumlu etki, muhtemelen kronik bariyer bozulmasının gerilemesi ve sıkı bağlantıların iyileşmesini temsil etmektedir. Enema kullanımında tercih edilen Lactobacillus probiyotik suşları, intestinal denge ile sonuçlanan bağırsak mikrobiyotasının manipüle edilmesi ile deri sağlığını potansiyel olarak düzenledi.
Anahtar Kelimeler: Kanin atopi; intestinal mikrobiyom; probiyotikler; rektal enema; zonulin
- O'Neill CA, Monteleone G, McLaughlin JT, Paus R. The gut-skin axis in health and disease: A paradigm with therapeutic implications. Bioessays. 2016;38(11):1167-76. [Crossref] [PubMed]
- De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-skin axis: current knowledge of the ınterrelationship between microbial dysbiosis and skin conditions. Microorganisms. 2021;9(2):353. [Crossref] [PubMed] [PMC]
- Nam B, Kim SA, Park SD, Kim HJ, Kim JS, Bae CH, et al. Regulatory effects of Lactobacillus plantarum HY7714 on skin health by improving intestinal condition. PLoS One. 2020;15(4):e0231268. [Crossref] [PubMed] [PMC]
- Han Y, Kim B, Ban J, Lee J, Kim BJ, Choi BS, et al. A randomized trial of Lactobacillus plantarum CJLP133 for the treatment of atopic dermatitis. Pediatr Allergy Immunol. 2012;23(7):667-73. [Crossref] [PubMed]
- Gueniche A, Philippe D, Bastien P, Reuteler G, Blum S, Castiel-Higounenc I, et al. Randomised double-blind placebo-controlled study of the effect of Lactobacillus paracasei NCC 2461 on skin reactivity. Benef Microbes. 2014;5(2):137-45. [Crossref] [PubMed]
- Olivry T, Saridomichelakis M, Nuttall T, Bensignor E, Griffin CE, Hill PB; International Committe on Allergic Diseases of Animals (ICADA). Validation of the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-4, a simplified severity scale for assessing skin lesions of atopic dermatitis in dogs. Vet Dermatol. 2014;25(2):77-85, e25. [Crossref] [PubMed]
- Hill PB, Lau P, Rybnicek J. Development of an owner-assessed scale to measure the severity of pruritus in dogs. Vet Dermatol. 2007;18(5):301-8. [Crossref] [PubMed]
- Cosgrove SB, Wren JA, Cleaver DM, Walsh KF, Follis SI, King VI, et al. A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (Apoquel®) in client-owned dogs with atopic dermatitis. Vet Dermatol. 2013;24(6):587-97, e141-2. [Crossref] [PubMed] [PMC]
- Comeau AM, Douglas GM, Langille MG. Microbiome helper: a custom and streamlined workflow for microbiome research. mSystems. 2017;2(1):e00127-16. [Crossref] [PubMed] [PMC]
- Pichler R, Fritz J, Tulchiner G, Klinglmair G, Soleiman A, Horninger W, et al. Increased accuracy of a novel mRNA-based urine test for bladder cancer surveillance. BJU Int. 2018;121(1):29-37. [Crossref] [PubMed]
- Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581-3. [Crossref] [PubMed] [PMC]
- Quast SA, Berger A, Eberle J. ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis. Cell Death Dis. 2013;4(10):e839. [Crossref] [PubMed] [PMC]
- Lee DB, Huang E, Ward HJ. Tight junction biology and kidney dysfunction. Am J Physiol Renal Physiol. 2006;290(1):F20-34. [Crossref] [PubMed]
- El Asmar R, Panigrahi P, Bamford P, Berti I, Not T, Coppa GV, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002;123(5): 1607-15. Erratum in: Gastroenterology 2003;124(1):275. El Asmar Rahzi [corrected to El Asmar Ramzi]. [Crossref] [PubMed]
- Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci. 2000;915:214-22. [Crossref] [PubMed]
- Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000;355(9214):1518-9. [Crossref] [PubMed]
- De Benedetto A, Rafaels NM, McGirt LY, Ivanov AI, Georas SN, Cheadle C, et al. Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol. 2011;127(3):773-86.e1-7. [Crossref] [PubMed] [PMC]
- Sheen YH, Jee HM, Kim DH, Ha EK, Jeong IJ, Lee SJ, et al. Serum zonulin is associated with presence and severity of atopic dermatitis in children, independent of total IgE and eosinophil. Clin Exp Allergy. 2018;48(8):1059-62. [Crossref] [PubMed]
- Ra J, Lee DE, Kim SH, Jeong JW, Ku HK, Kim TY, et al. Effect of oral administration of Lactobacillus plantarum HY7714 on epidermal hydration in ultraviolet B-irradiated hairless mice. J Microbiol Biotechnol. 2014;24(12): 1736-43. [Crossref] [PubMed]
- Lee DE, Huh CS, Ra J, Choi ID, Jeong JW, Kim SH, et al. Clinical evidence of effects of Lactobacillus plantarum HY7714 on skin aging: a randomized, double blind, placebo-controlled study. J Microbiol Biotechnol. 2015;25(12):2160-8. [Crossref] [PubMed]
- Ahrne S, Hagslatt ML. Effect of lactobacilli on paracellular permeability in the gut. Nutrients. 2011;3(1):104-17. [Crossref] [PubMed] [PMC]
- Nam B, Kim SA, Nam W, Jeung WH, Park SD, Lee JL, et al. Lactobacillus plantarum HY7714 restores TNF-α induced defects on tight junctions. Prev Nutr Food Sci. 2019;24(1):64-9. [Crossref] [PubMed] [PMC]
- Karczewski J, Troost FJ, Konings I, Dekker J, Kleerebezem M, Brummer RJ, et al. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol. 2010;298(6):G851-9. [Crossref] [PubMed]
- Sultana R, McBain AJ, O'Neill CA. Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates. Appl Environ Microbiol. 2013;79(16):4887-94. [Crossref] [PubMed] [PMC]
- Rittirsch D, Flierl MA, Nadeau BA, Day DE, Huber-Lang MS, Grailer JJ, et al. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system. Am J Physiol Lung Cell Mol Physiol. 2013;304(12):L863-72. [Crossref] [PubMed] [PMC]
- Pacifico L, Bonci E, Marandola L, Romaggioli S, Bascetta S, Chiesa C. Increased circulating zonulin in children with biopsy-proven nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(45):17107-14. [Crossref] [PubMed] [PMC]
- Küme T, Acar S, Tuhan H, Çatlı G, Anık A, Gürsoy Çalan Ö, et al. The relationship between serum zonulin level and clinical and laboratory parameters of childhood obesity. J Clin Res Pediatr Endocrinol. 2017;9(1):31-8. Erratum in: J Clin Res Pediatr Endocrinol. 2020;12(3):331. [Crossref] [PubMed] [PMC]
- Yamaide F, Fikri B, Nakano T, Shimojo N. Serum zonulin levels are higher in pediatric allergic patients than those in healthy children. World Allergy Organ J. 2020;13(8):122. [Crossref]
- Cukrowska B, Ceregra A, Maciorkowska E, Surowska B, Zegadło-Mylik MA, Konopka E, et al. The effectiveness of probiotic Lactobacillus rhamnosus and Lactobacillus casei strains in children with atopic dermatitis and cow's milk protein allergy: a multicenter, randomized, double blind, placebo controlled study. Nutrients. 2021;13(4):1169. [Crossref] [PubMed] [PMC]
- Brown M. Modes of action of probiotics: recent developments. J Anim Vet Adv. 2011;10(14):1895-900. [Crossref]
- Bajaj BK, Claes IJ, Lebeer S. Functional mechanisms of probiotics. JMBFS. 2015;4(4):321-7. [Crossref]
- Kim WK, Jang YJ, Seo B, Han DH, Park S, Ko G. Administration of Lactobacillus paracasei strains improves immunomodulation and changes the composition of gut microbiota leading to improvement of colitis in mice. J Funct Foods. 2019;52:565-75. [Crossref]
- Surono IS, Nishigaki T, Endaryanto A, Waspodo P. Indonesian biodiversities, from microbes to herbal plants as potential functional foods. Journal of the Faculty of Agriculture Shinshu University. 2008;44(1):23-7. [Link]
- Prakoeswa CRS, Herwanto N, Prameswari R, Astari L, Sawitri S, Hidayati AN, et al. Lactobacillus plantarum IS-10506 supplementation reduced SCORAD in children with atopic dermatitis. Benef Microbes. 2017;8(5):833-40. [Crossref] [PubMed]
- Ural K. Veteriner İç Hastalıklarında Probiyotikler Probiyotik Kullanımı Rehber Kitabı ve Olgu Atlası. 1. Baskı. Ankara: Yayın Yeri: Atalay Konfeksiyon Matbaacılık ve Reklamcılık İnşaat Turizm Otomotiv San. ve Tic. Ltd. Sti.; 2020.
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