Comparative analysis of serum levels of zonulin in healthy donors and patients with inflammatory bowel diseases

Н.Н. Зыбина; Е.П. Салянова; Ю.С. Тимофеев; А.А. Алферов; О.В. Ковалева; П.В. Царапаев; Н.В. Любимова

doi:10.18127/j20700997-202203-02

Comparative analysis of serum levels of zonulin in healthy donors and patients with inflammatory bowel diseases

Н.Н. Зыбина¹, Е.П. Салянова², Ю.С. Тимофеев³, А.А. Алферов⁴, О.В. Ковалева⁵, П.В. Царапаев⁶, Н.В. Любимова⁷

research article UDC 616.34-002+577.112 Pages: 15-21 doi.org/10.18127/j20700997-202203-02

¹ ФГБУ «Всероссийский центр экстренной и радиационной медицины имени А.М. Никифорова»
^2,3,4,7 ФГБОУ ВО «МГМСУ им. А.И. Евдокимова» Минздрава России (Москва, Россия)
^5,6 ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»

Keywords: Zonulin blood serum inflammatory bowel disease

Abstract

Zonulin is involved in the regulation of intestinal permeability and is closely associated with innate intestinal immunity. Changes in the permeability of the intestinal wall as a result of impaired tight junctions are associated with the pathogenesis of many autoimmune diseases, including various inflammatory processes in the intestine, which may be accompanied by increased secretion of zonulin.

The aim of the work is a comparative analysis of the level of zonulin in the blood serum of healthy donors and patients with various inflammatory bowel diseases.

Comparative enzyme immunoassay of zonulin serum levels in 63 healthy (control group; 33 men and 30 women; age 20-68 years) and 75 patients (28 men and 47 women; age 18-70 years) with inflammatory bowel disease revealed that the zonulin levels are not associated with age, however, in the control group, the average levels of the factor were statistically significantly lower in women (30.9±2.2 ng/ml) than in men (39.4±3.2 ng/ml) (p=0.037) and significantly lower compared to the general group of patients with inflammatory bowel diseases (35.4±2.1 and 49.4±2.0 ng/ml, respectively; p=0.0000001). An analysis of the levels of zonulin in the blood serum of patients with various types of inflammatory bowel diseases was carried out. It was found that the average level of zonulin in the blood serum of the control group was statistically significantly lower (p<0.05) than in patients with mixed irritable bowel syndrome (55.7±2.9 ng/ml), with ulcerative colitis (54.6±3.8 ng/ml), with Crohn's disease (54.5±10.1 ng/ml). It was found that serum concentrations of zonulin did not differ between the control group and patients with functional bowel disorders (37.8±4.9 ng/ml), irritable bowel syndrome with diarrhea (44.9±5.7 ng/ml), irritable bowel syndrome intestines with a tendency to constipation (41.7±5.1 ng/ml).

The possibilities of using serum zonulin in the diagnosis of various inflammatory bowel diseases are discussed.

Received: 15.08.2022
Approved after review: 15.08.2022
Accepted: 25.08.2022

How to cite

Зыбина Н.Н., Салянова Е.П., Тимофеев Ю.С., Алферов А.А., Ковалева О.В., Царапаев П.В., Любимова Н.В., Никонов Е.Л., Кушлинский Н.Е. Сравнительный анализ сывороточных уровней зонулина у здоровых доноров и больных воспалительными заболеваниями кишечника // Технологии живых систем. 2022. T. 19. № 3. С. 15-21. DOI: https://doi.org/10.18127/j20700997-202203-02

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[1] Fasano A., Not T., Wang W., Uzzau S., Berti I., Tommasini A., Goldblum S.E. Zonulin, a Newly Discovered Modulator of Intestinal Permeability, and Its Expression in Coeliac Disease. Lancet. 2000. V. 355. № 9214. P. 1518–1519.

[2] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol. Rev. 2011. V. 91. № 1. P. 151–175. Doi: 10.1152/physrev.00003.2008

[3] Tripathi A., Lammers K.M., Goldblum S., Shea-Donohue T., Netzel-Arnett S., Buzza M.S., Antalis T.M., Vogel S.N., Zhao A., Yang S., Arrietta M.C., Meddings J.B., Fasano A. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc. Natl Acad. Sci. USA. 2009. V. 106. № 39. P. 16799–16804. Doi: 10.1073/pnas.0906773106

[4] Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020. V. 9. ID F1000 Faculty Rev-69. Doi: 10.12688/f1000research.20510.1

[5] Barbaro M.R., Cremon C., Morselli-Labate A.M., Di Sabatino A., Giuffrida P., Corazza G.R., Di Stefano M., Caio G., Latella G., Ciacci C., Fuschi D., Mastroroberto M., Bellacosa L., Stanghellini V., Volta U., Barbara G. Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity. Gut. 2020. V. 69. № 11. P. 1966–1974. Doi: 10.1136/gutjnl-2019-319281

[6] Zybina N.N., Nikonov E.L., Gershtein E.S., Memdli Z.Z., Stilidi I.S., Kushlinskii N.E. Zonulin is a marker of epithelial and endothelial barrier functions in non-communicable diseases (narrative review). Russian J. Evidence-based Gastroenterology = Dokazatel’naya gastroenterologiya. 2022. V. 11. № 1. P. 28–44.

[7] Esnafoglu E., Cırrık S., Ayyıldız S.N., Erdil A., Ertürk E.Y., Daglı A., Noyan T. Increased Serum Zonulin Levels as an Intestinal Permeability Marker in Autistic Subjects. J. Pediatr. 2017. V. 188. P. 240–244. Doi: 10.1016/j.jpeds.2017.04.004

[8] Malíčková K., Francová I., Lukáš M., Kolář M., Králíková E., Bortlík M., Ďuricová D., Štěpánková L., Zvolská K., Pánková A., Zima T. Fecal zonulin is elevated in Crohn's disease and in cigarette smokers. Pract. Lab. Med. 2017. V. 9. P. 39–44. Doi: 10.1016/j.plabm.2017.09.001

[9] Sturgeon C., Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016. V. 4. № 4. ID e1251384.

[10] Meira de-Faria F., Bednarska O., Ström M., Söderholm J.D., Walter S.A., Keita Å.V. Colonic paracellular permeability and circulating zonulin-related proteins. Scand. J. Gastroenterol. 2021. V. 56. № 4. P. 424–431. Doi: 10.1080/00365521. 2021.1879247

[11] Wang W., Uzzau S., Goldblum S.E., Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J. Cell. Sci. 2000. V. 113. Pt 24. P. 4435–4440

[12] Di Pierro M., Lu R., Uzzau S., Wang W., Margaretten K., Pazzani C., Maimone F., Fasano A. Zonula occludens toxin structure-function analysis. Identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain. J. Biol. Chem. 2001. V. 276. № 22. P. 19160–19165.

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