Association between morphological manifestations of inflammatory bowel disease and biochemical markers of inflammation

Authors

DOI:

https://doi.org/10.14739/2310-1210.2022.6.260285

Keywords:

histology, nonspecific ulcerative colitis, Crohn’s disease, calprotectin, short-chain volatile fatty acids

Abstract

Aim. To determine morphological and morphometric changes in the structure of the mucous membrane of the large intestine and their relationship with the content of short-chain volatile fatty acids and fecal calprotectin in patients with inflammatory bowel disease.

Materials and methods. We examined 68 patients with inflammatory bowel disease, including 30 women and 38 men aged 20–66 years, 55 patients were with ulcerative colitis and 13 patients – with Crohn’s disease. Histological examination focused on changes in the mucous membrane of the large intestine. Determination of short-chain volatile fatty acids in feces was performed using gas chromatography. Calprotectin content was measured in fecal samples by enzyme-linked immunosorbent assay.

Results. Significant correlations were found between epithelial disruption and changes in crypt architecture, infiltration density, and histological activity. The higher degree of inflammation in patients with severe course was combined with a lower level of tissue nonspecific protection, which was detected by the number of goblet cells, eosinophilic and neutrophilic leukocytes. There was a decrease in the fecal concentration of butyric acid in patients with nonspecific ulcerative colitis and Crohn’s disease compared with controls, but a more significant decrease was observed in patients with severe nonspecific ulcerative colitis.

The data have confirmed the association between inflammatory bowel disease and the content of short-chain volatile fatty acids, fecal calprotectin in coprofiltrate, which was evidenced by the presence of correlations between low content of short-chain volatile fatty acids and eosinophilic infiltration (r = -0.412; fecal calprotectin levels and disease severity (r = 0.589; P = 0.001), atrophy (r = 0.458; Р < 0.05), infiltration density (r = 0.434; Р < 0.05).

Conclusions. All patients with inflammatory bowel disease are characterized by a specific histological picture, which reflected the different degrees of inflammation. Morphometric parameters more accurately show significant atrophic changes in the mucous membrane of the large intestine. The data have confirmed the association between inflammatory bowel disease and the content of short-chain volatile fatty acids and calprotectin in coprofiltrate.

Author Biographies

M. V. Stoikevych, SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro

MD, PhD, Head of the Department of Intestinal Diseases

Yu. A. Haidar

MD, PhD, DSc, Head of the Pathomorphological Laboratory

D. F. Mylostуva, SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro

PhD, Senior Researcher the Pathomorphological Laboratory

I. A. Klenina, SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro

PhD, Head of the Research Sector

O. M. Tatarchuk, SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro

PhD, Senior Researcher of the Research Sector

V. A. Karachynova V. A., , SI “Institute of Gastroenterology of the National Academy of Medical Sciences of Ukraine”, Dnipro

PhD, Senior Researcher of the Research Sector

References

Sairenji, T., Collins, K. L., & Evans, D. V. (2017). An Update on Inflammatory Bowel Disease. Primary care, 44(4), 673-692. https://doi.org/10.1016/j.pop.2017.07.010

Ahluwalia, B., Moraes, L., Magnusson, M. K., & Öhman, L. (2018). Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies. Scandinavian journal of gastroenterology, 53(4), 379-389. https://doi.org/10.1080/00365521.2018.1447597

Kikut, J., Mokrzycka, M., Drozd, A., Grzybowska-Chlebowczyk, U., Ziętek, M., & Szczuko, M. (2022). Involvement of Proinflammatory Arachidonic Acid (ARA) Derivatives in Crohn's Disease (CD) and Ulcerative Colitis (UC). Journal of clinical medicine, 11(7), 1861. https://doi.org/10.3390/jcm11071861

Ng, S. C., Shi, H. Y., Hamidi, N., Underwood, F. E., Tang, W., Benchimol, E. I., Panaccione, R., Ghosh, S., Wu, J., Chan, F., Sung, J., & Kaplan, G. G. (2017). Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet, 390(10114), 2769-2778. https://doi.org/10.1016/S0140-6736(17)32448-0

Sheng, Q., Li, F., Chen, G., Li, J., Li, J., Wang, Y., Lu, Y., Li, Q., Li, M., & Chai, K. (2021). Ursolic Acid Regulates Intestinal Microbiota and Inflammatory Cell Infiltration to Prevent Ulcerative Colitis. Journal of immunology research, 2021, 6679316. https://doi.org/10.1155/2021/6679316

Banfi, D., Moro, E., Bosi, A., Bistoletti, M., Cerantola, S., Crema, F., Maggi, F., Giron, M. C., Giaroni, C., & Baj, A. (2021). Impact of Microbial Metabolites on Microbiota-Gut-Brain Axis in Inflammatory Bowel Disease. International journal of molecular sciences, 22(4), 1623. https://doi.org/10.3390/ijms22041623

Chelakkot, C., Ghim, J., & Ryu, S. H. (2018). Mechanisms regulating intestinal barrier integrity and its pathological implications. Experimental & molecular medicine, 50(8), 1-9. https://doi.org/10.1038/s12276-018-0126-x

Wang, X., Tang, Q., Hou, H., Zhang, W., Li, M., Chen, D., Gu, Y., Wang, B., Hou, J., Liu, Y., & Cao, H. (2021). Gut Microbiota in NSAID Enteropathy: New Insights From Inside. Frontiers in cellular and infection microbiology, 11, 679396. https://doi.org/10.3389/fcimb.2021.679396

Gasaly, N., de Vos, P., & Hermoso, M. A. (2021). Impact of Bacterial Metabolites on Gut Barrier Function and Host Immunity: A Focus on Bacterial Metabolism and Its Relevance for Intestinal Inflammation. Frontiers in immunology, 12, 658354. https://doi.org/10.3389/fimmu.2021.658354

Maglione, A., Zuccalà, M., Tosi, M., Clerico, M., & Rolla, S. (2021). Host Genetics and Gut Microbiome: Perspectives for Multiple Sclerosis. Genes, 12(8), 1181. https://doi.org/10.3390/genes12081181

van de Wouw, M., Boehme, M., Lyte, J. M., Wiley, N., Strain, C., O'Sullivan, O., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2018). Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. The Journal of physiology, 596(20), 4923-4944. https://doi.org/10.1113/JP276431

Lavelle, A., & Sokol, H. (2020). Gut microbiota-derived metabolites as key actors in inflammatory bowel disease. Nature reviews. Gastroenterology & hepatology, 17(4), 223-237. https://doi.org/10.1038/s41575-019-0258-z

Agus, A., Clément, K., & Sokol, H. (2021). Gut microbiota-derived metabolites as central regulators in metabolic disorders. Gut, 70(6), 1174-1182. https://doi.org/10.1136/gutjnl-2020-323071

Chen, M. X., Wang, S. Y., Kuo, C. H., & Tsai, I. L. (2019). Metabolome analysis for investigating host-gut microbiota interactions. Journal of the Formosan Medical Association = Taiwan yi zhi, 118 Suppl 1, S10-S22. https://doi.org/10.1016/j.jfma.2018.09.007

Jones R. L. (2022). Gut microbiome as a potential biomarker of cancer risk in inflammatory bowel disease. Contemporary oncology, 26(1), 40-43. https://doi.org/10.5114/wo.2022.114537

Fobofou, S. A., & Savidge, T. (2022). Microbial metabolites: cause or consequence in gastrointestinal disease?. American journal of physiology. Gastrointestinal and liver physiology, 322(6), G535-G552. https://doi.org/10.1152/ajpgi.00008.2022

Debnath, N., Kumar, R., Kumar, A., Mehta, P. K., & Yadav, A. K. (2021). Gut-microbiota derived bioactive metabolites and their functions in host physiology. Biotechnology & genetic engineering reviews, 37(2), 105-153. https://doi.org/10.1080/02648725.2021.1989847

Seyedian, S. S., Nokhostin, F., & Malamir, M. D. (2019). A review of the diagnosis, prevention, and treatment methods of inflammatory bowel disease. Journal of medicine and life, 12(2), 113-122. https://doi.org/10.25122/jml-2018-0075

Khaki-Khatibi, F., Qujeq, D., Kashifard, M., Moein, S., Maniati, M., & Vaghari-Tabari, M. (2020). Calprotectin in inflammatory bowel disease. Clinica chimica acta; international journal of clinical chemistry, 510, 556-565. https://doi.org/10.1016/j.cca.2020.08.025

Sivaprakasam, S., Bhutia, Y. D., Yang, S., & Ganapathy, V. (2017). Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis. Comprehensive Physiology, 8(1), 299-314. https://doi.org/10.1002/cphy.c170014

Li, G., Lin, J., Zhang, C., Gao, H., Lu, H., Gao, X., Zhu, R., Li, Z., Li, M., & Liu, Z. (2021). Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease. Gut microbes, 13(1), 1968257. https://doi.org/10.1080/19490976.2021.1968257

Ferrer-Picón, E., Dotti, I., Corraliza, A. M., Mayorgas, A., Esteller, M., Perales, J. C., Ricart, E., Masamunt, M. C., Carrasco, A., Tristán, E., Esteve, M., & Salas, A. (2020). Intestinal Inflammation Modulates the Epithelial Response to Butyrate in Patients With Inflammatory Bowel Disease. Inflammatory bowel diseases, 26(1), 43-55. https://doi.org/10.1093/ibd/izz119

Siddiqui, M. T., & Cresci, G. (2021). The Immunomodulatory Functions of Butyrate. Journal of inflammation research, 14, 6025-6041. https://doi.org/10.2147/JIR.S300989

Fukunaga, S., Kuwaki, K., Mitsuyama, K., Takedatsu, H., Yoshioka, S., Yamasaki, H., Yamauchi, R., Mori, A., Kakuma, T., Tsuruta, O., & Torimura, T. (2018). Detection of calprotectin in inflammatory bowel disease: Fecal and serum levels and immunohistochemical localization. International journal of molecular medicine, 41(1), 107-118. https://doi.org/10.3892/ijmm.2017.3244

Gaydar, Y., Stoykevich, M., Sіmonova O., Milostiva, D., Tіtova M., & Nedzvetska, N. (2021). Gender- and age-related features of the morphological state of the mucous membrane of the colon in patients with chronic inflammatory bowel diseases. Gastroenterologìa, 54(1), 24-29. https://doi.org/10.22141/2308-2097.54.1.2020.199138

Dalile, B., Van Oudenhove, L., Vervliet, B., & Verbeke, K. (2019). The role of short-chain fatty acids in microbiota-gut-brain communication. Nature reviews. Gastroenterology & hepatology, 16(8), 461-478. https://doi.org/10.1038/s41575-019-0157-3

Zaichenko, K., Gavrylyuk, V., Klenina, I., Sklyar, T., Sokolova, I., Tatarchuk, O., & Vishnarevskaya, N. (2020). Determination of the intestinal microbiome composition in patients with crohn's disease and ulcerative colitis of different age categories and sex. Ukrainskyi zhurnal medytsyny, biolohii ta sportu, 5(3), 273-281. https://doi.org/10.26693/jmbs05.03.273

Psareva, I. V. (2020). Zviazok biomarkeriv zapalennia v tovstii kyshtsi z indeksamy aktyvnosti nespetsyfichnoho vyrazkovoho kolitu [Association of biomarkers of intestinal inflammation with indexes of ulcerative colitis activity]. Gastroenterologìa, 54(1), 38-43. [in Ukrainian]. https://doi.org/10.22141/2308-2097.54.1.2020.199140

Gionchetti, P., Dignass, A., Danese, S., Magro Dias, F. J., Rogler, G., Lakatos, P. L., Adamina, M., Ardizzone, S., Buskens, C. J., Sebastian, S., Laureti, S., Sampietro, G. M., Vucelic, B., van der Woude, C. J., Barreiro-de Acosta, M., Maaser, C., Portela, F., Vavricka, S. R., Gomollón, F., & ECCO (2017). 3rd European Evidence-based Consensus on the Diagnosis and Management of Crohn's Disease 2016: Part 2: Surgical Management and Special Situations. Journal of Crohn's & colitis, 11(2), 135-149. https://doi.org/10.1093/ecco-jcc/jjw169

Restellini, S., Chao, C. Y., Martel, M., Barkun, A., Kherad, O., Seidman, E., Wild, G., Bitton, A., Afif, W., Bessissow, T., & Lakatos, P. L. (2019). Clinical Parameters Correlate With Endoscopic Activity of Ulcerative Colitis: A Systematic Review. Clinical gastroenterology and hepatology, 17(7), 1265-1275.e8. https://doi.org/10.1016/j.cgh.2018.12.021

Kaczmarczyk, O., Dąbek-Drobny, A., Woźniakiewicz, M., Paśko, P., Dobrowolska-Iwanek, J., Woźniakiewicz, A., Piątek-Guziewicz, A., Zagrodzki, P., Mach, T., & Zwolińska-Wcisło, M. (2021). Fecal Levels of Lactic, Succinic and Short-Chain Fatty Acids in Patients with Ulcerative Colitis and Crohn Disease: A Pilot Study. Journal of clinical medicine, 10(20), 4701. https://doi.org/10.3390/jcm10204701

Downloads

Published

2022-12-20

How to Cite

1.
Stoikevych MV, Haidar YA, Mylostуva DF, Klenina IA, Tatarchuk OM, Karachynova V. A., VA. Association between morphological manifestations of inflammatory bowel disease and biochemical markers of inflammation. Zaporozhye Medical Journal [Internet]. 2022Dec.20 [cited 2024Jul.3];24(6):665-73. Available from: http://zmj.zsmu.edu.ua/article/view/260285

Issue

Vol. 24 No. 6 (2022)

Section

Original research

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.  Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)