Pathogenetic role of changes in the colon mucous barrier in patients with ulcerative colitis and the possibility of correction
Authors: Dorofeyev A. E. , Tkach S. M. , Dyadyk O. O. , Kryvoruk O. M. , Hurkalo Y. Z. 
Published: October 2024

The aim of this study was to evaluate the changes in the colon mucosal barrier in patients with ulcerative colitis (UC) and to analyze the efficacy of using Zafacol IQ in the complex therapy of these patients.
Materials and methods. A prospective, multicenter, randomized, comparative study was conducted in parallel groups to investigate the efficacy and safety of the Zafacol IQ administration in the complex therapy of patients with UC. 64 patients with left‑sided UC of medium‑severe course in the acute stage were observed. There were 34 men and 30 women among the patients; the average age was (46.6±5.8) years. The diagnosis of UC was established clinically and confirmed endoscopically and histologically. The study included patients suffering from UC for at least 1 year. All patients underwent endoscopic examination of the large intestine with biopsy before treatment and after 6 weeks of therapy. The biopsy was stained with hematoxylin and eosin; the PAS reaction was performed. To determine the content of mucins in colonic mucus and the state of tight junctions, an immunohistochemical study was conducted with mucins (MUC‑2, MUC‑4) and proteins of the tight junction family Claud‑1 and Claud‑7. Before and after therapy, the status of the main bacterial enterotypes (Bacteroidetes, Firmicutes, Actinobacteria), as well as the level of regulatory, butyrate‑producing bacteria (Faecalibacterium prausnitzii, Akkermansia muciniphila) were studied in all patients using the polymerase chain reaction qRT‑PCR method.
Results. Before therapy, against the background of the development of clinical symptoms, UC patients had a violation of the integrity of the epithelium with the formation of erosive‑ulcerative defects and changes in the colon mucous membrane with the development of inflammatory cell infiltration and disorders of mucus formation and increased epithelial permeability. Before treatment, changes in the colon microbial landscape were detected in UC patients, with a significant decrease in Bacteroidetes and Firmicutes against the background of an increase in representatives of Actinobacteria and other, mostly opportunistic flora. In addition, a reduction in the regulatory butyrate‑producing bacteria (Akkermansia muciniphila and Faecalibacterium prausnitzii) was fixed in patients with UC. The use of Zafacol IQ in patients contributed to a lower level of clinical activity of the disease, increased the frequency of achieving endoscopic remission of UC after complex treatment, led to a decrease in active neutrophils in the cellular infiltrate, improved mucus formation with tendencies to normalize its quality characteristics, an increase in glycoproteins and glycosaminoglycans, as well as MUC2 in colonic mucus, contributed to a decrease in epithelial permeability and an increase in the expression of Claud­­1 and Claud­­7 in goblet cells with an increase in Bacteroidetes, Firmicutes and Faecalibacterium prausnitzii.
Conclusions. The use of Zafacol IQ in the complex therapy of UC patients was effective and safe. This drug in combination with mesalazine contributed to positive clinical dynamics and a lower level of clinical activity of the disease, increased the frequency of endoscopic remission of UC. Pronounced positive morphological dynamics were observed: an improvement in mucus formation, an increase in the intensity of the PAS reaction, an increase in MUC2 in the colonic mucus, a decrease in epithelial permeability, and an increase in the expression of Claud‑1 and Claud‑7 in both goblet cells and in the surface epithelium. Complex therapy with the appointment of ­Zafacol IQ contributed to the normalization of the intestinal microbiome in UC patients — an increase in Bacteroidetes, Firmicutes and Faecalibacterium prausnitzii with a tendency to decrease Actinobacteria.