Can fecal zonulin be used as a biomarker in the detection of leaky bowel syndrome in patients with intestinal metaplasia? A prospective cross-sectional study

Öz

Abstract: Aim: Intestinal metaplasia is the most common finding in routine endoscopic studies. The relationship between intestinal metaplasia and intestinal dysbiosis and leaking intestine is now a known fact. In this study, we tried to show the detection of this chain of events, which may cause many diseases, with zonulin in stool, which is a non-invasive method. Material and Method: Endoscopy was performed on 20 patients with dyspeptic complaints as of January 2022. All patients were tested for zonulin in the stool using the Stool Sample Application System (SAS) and Elisa method. Endoscopic findings of the patients (intestinal metaplasia, atrophic gastritis, helicobacter (Hp) status) and zonulin values in the stool were examined. This study was designed as a prospective cross-sectional study. Results: The median age of the patients was 48.35 (December: 33-73). In this study, 40% of the patients were female and 60% were male. Of the 20 patients who underwent endoscopy, 14 had intestinal metaplasia (70%), 11 had atrophic gastritis (55%) and 14 had helicobacter (Hp). In our results, while zonulin was high in stool in all patients with these conditions, only statistical significance was observed between intestinal metaplasia and zonulin elevation. Conclusion: Zonulin excretion has increased in fecal excretion in cases with intestinal metaplasia and may be an important marker in these cases.

Anahtar Kelimeler

• zonulin
• intestinal permeability
• atrophic gastritis
• intestinal metaplasia

İntestinal metaplazili hastalarda sızdıran bağırsak sendromu tespitinde fekal zonulin biomarker olarak kullanılabilir mi?: prospektif kesitsel çalışma

Öz

Amaç: intestinal metaplazi, rutin endoskopik çalışmalarda en sık görülen bulgudur. İntestinal metaplazi ile bağırsak disbiyozu ve sızdıran bağırsak arasındaki ilişki artık bilinen bir gerçektir. Biz bu çalışmamızda bir çok hastalığa neden olabilen bu olaylar zincirini non invazif yöntem olan gaitada zonulin ile tespitini göstermeye çalıştık. Materiyal ve Metod : Ocak 2022 den itibaren dispeptik şikayetleri olan 20 hastaya endoskopi yapıldı.. Hastaların hepsinden, Stool Sample Application System (SAS) ve Elisa yöntemi ile gaitada zonulin bakıldı. Hastaların endoskopik bulguları (intestinal metaplazi, atrofik gastrit, helicobakter(Hp) durumu) ile gaitada zonulin değerleri incelendi. Prospektif kesitsel çalışma olarak dizayn edildi. Bulgular: Hastaların median yaşı 48.35( Aralık:33-73) ti. Hastaların %40 ı kadın %60 ı erkekti. Endoskopi yapılan 20 hastadan, 14 hastada intestinal metaplazi (%70), 11 hastada atrofik gastrit (%55) ve 14 hastada helikobakter (Hp) saptadık. Sonuçlarımızda bu durumların var olduğu tüm hastalarda gaitada zonulin yüksek saptanırken, sadece intestinal metaplazi ile zonulin yüksekliği arasında istatistiksel anlamlılık gözlenmiştir. Sonuç: Zonulin atılımı intestinal metaplazili olgularda dışkıda atılımı artmıştır ve bu olgularda önemli bir belirteç olabilir.

Anahtar Kelimeler

• zonulin
• bağırsak geçirgenliği
• atrofik gastrit
• intestinal metaplazi

Kaynakça

1. 1. Putignani L, Del Chierico F, Vernocchi P, et al; Dysbiotrack Study Group. Gut Microbiota Dysbiosis as Risk and Premorbid Factors of IBD and IBS Along the Childhood-Adulthood Transition. |Inflamm Bowel Dis. 2016 Feb;22(2): 487-504. doi: 10.1097/MIB.0000000000000602.
2. 2. Zhang R, Zhang J, Dang W, et al. Unveiling the Biogeography and Potential Functions of the Intestinal Digesta- and Mucosa-Associated Microbiome of Donkeys. Front Microbiol. 2020 Dec 4; 11: 596882. doi: 10.3389/fmicb.2020.596882.
3. 3. Li J , Wu T , Li N , et al. Bilberry anthocyanin extract promotes intestinal barrier function and inhibits digestive enzyme activity by regulating the gut microbiota in aging rats. Food Funct. 2019 Jan 22; 10 (1): 333-343. doi: 10.1039/c8fo01962b.
4. 4. Park CH, Lee AR, Lee YR, et al. Evaluation of gastric microbiome and metagenomic function in patients with intestinal metaplasia using 16S rRNA gene sequencing. Helicobacter 2019 Feb;24(1): e12547. doi: 10.1111/hel.12547. Epub 2018 Nov 15.
5. 5. Sharma BK, Santana IA, Wood EC, et al. Intragastric bacterial activity and nitrosation before, during, and after treatment with omeprazole. Br Med J (Clin Res Ed). 1984 Sep 22; 289 (6447): 717-9. doi: 10.1136/bmj.289.6447.717.
6. 6. Park YH, Kim N. Review of atrophic gastritis and intestinal metaplasia as a premalignant lesion of gastric cancer. J Cancer Prev. 2015 Mar;20(1): 25-40. doi: 10.15430/JCP.2015.20.1.25.
7. 7. Oliphant K,Allen-Vercoe E. Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health. Microbiome. 2019 Jun 13; 7 (1): 91. doi: 10.1186/s40168-019-0704-8.
8. 8. Zeng J, Yan R, Pan H, et al. Weipixiao attenuate early angiogenesis in rats with gastric precancerous lesions. BMC Complement Alternative Med. 2018 Sep 10; 18 (1): 250. doi: 10.1186/s12906-018-2309-3.

9. 9. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21; 4 (4): e1251384. doi: 10.1080/21688370.2016.1251384.
10. 10. Fasano A. Intestinal permeability and its regulation by zonulin: diagnostic and therapeutic implications. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1096-100. doi: 10.1016/j.cgh.2012.08.012. Epub 2012 Aug 16.
11. 11. El Asmar R, Panigrahi P, Bamford P, et al. Host-dependent zonulin secretion causes the impairment of the small intestine barrier function after bacterial exposure. Gastroenterology. 2002 Nov;123(5): 1607-15. doi: 10.1053/gast.2002.36578. Erratum in: Gastroenterology 2003 Jan;124(1):275. El Asmar Rahzi [corrected to El Asmar Ramzi].
12. 12. Valitutti F, Fasano A. Breaking Down Barriers: How Understanding Celiac Disease Pathogenesis Informed the Development of Novel Treatments. Dig Dis Sci. 2019 Jul;64(7): 1748-1758. doi: 10.1007/s10620-019-05646-y. PMID: 31076989
13. 13. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Surg Pathol. 2008 Nov;173(5): 1243-52. doi: 10.2353/ajpath.2008.080192. Epub 2008 Oct 2.
14. 14. Yu QH, Yang Q. Diversity of tight junctions (TJs) between gastrointestinal epithelial cells and their function in maintaining the mucosal barrier. Cell Biol Int. 2009 Jan;33(1): 78-82. doi: 10.1016/j.cellbi.2008.09.007. Epub 2008 Oct 7. PMID: 18938254.
15. 15. Wang W, Uzzau S, Goldblum SE, et al. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000 Dec;113 Pt 24: 4435-40. doi: 10.1242/jcs.113.24.4435.
16. 16. Drago S, El Asmar R, Di Pierro M, et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4): 408-19. doi: 10.1080/00365520500235334.
17. 17. Sapone A, de Magistris L, Pietzak M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. diabetes 2006 May;55(5): 1443-9. doi: 10.2337/db05-1593.
18. 18. Szymanska E, Wierzbicka A, Dadalski M, et al. Fecal Zonulin as a Noninvasive Biomarker of Intestinal Permeability in Pediatric Patients with Inflammatory Bowel Disease-Correlation with Disease Activity and Fecal Calprotectin. J Clin Anal Med. 2021 Aug 30; 10 (17): 3905. doi: 10.3390/jcm10173905. PMID: 34501351
19. 19. Turner D, Levine A, Walters TD, et al. Which PCDAI Version Best Reflects Intestinal Inflammation in Pediatric Crohn's Disease? J Pediatr Gastroenterol Nutr. 2017 Feb;64(2): 254-260. doi: 10.1097/MPG.0000000000001227.