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Інформація × Реєстраційний номер 2124U003015, Матеріали видань та локальних репозитаріїв Категорія Стаття Назва роботи The long-term consequences of antibiotic therapy: Role of colonic short-chain fatty acids (SCFA) system and intestinal barrier integrity Автор Yuliia HolotaTaisa DovbynchukIzumi KajiIgor VareniukNatalia DzyubenkoTetiana ChervinskaLiudmyla ZakordonetsViktoria StetskaLiudmyla OstapchenkoTetiana SerhiychukTolstanova Ganna Дата публікації 01-05-2024 Постачальник інформації Інституційний репозитарій (електронний архів) Київського національного університету імені Тараса Шевченка Першоджерело https://ir.library.knu.ua/handle/123456789/562 Видання Public Library of Science (PLoS) Опис Epidemiological studies revealed that antibiotics exposure increases a risk of inflammatory bowel diseases (IBD) development. It remained largely unknown how antibiotic-induced dysbiosis confers the risk for enhanced inflammatory response. The aim of the present study was to test the hypothesis that SCFAs, their receptors and transporters mediate the antibiotic long-term effects on the functional state of colonic mucosa and susceptibility to the experimental colitis. Male Wistar rats were treated daily for 14 days with antibiotic ceftriaxone (300 mg/kg, i.m.) or vehicle; euthanized by CO2 inhalation followed by cervical dislocation in 1, 14 or 56 days after antibiotic withdrawal. We found increased cecum weight and sustained changes in microbiota composition after ceftriaxone treatment with increased number of conditionally pathogenic enterobacteria, E. coli, Clostridium, Staphylococcus spp. and hemolytic bacteria even at 56 days after antibiotic withdrawal. The concentration of SCFAs was decreased after ceftriaxone withdrawal. We found decreased immunoreactivity of the FFA2, FFA3 receptors, SMCT1 and increased MCT1 & MCT4 transporters of SCFAs in colon mucosa. These changes evoked a significant shift in colonic mucosal homeostasis: the disturbance of oxidant-antioxidant balance; activation of redox-sensitive transcription factor HIF1α and ERK1/2 MAP kinase; increased colonic epithelial permeability and bacterial translocation to blood; morphological remodeling of the colonic tissue. Ceftriaxone pretreatment significantly reinforced inflammation during experimental colitis 56 days after ceftriaxone withdrawal, which was confirmed by increased histopathology of colitis, Goblet cell dysfunction, colonic dilatation and wall thickening, and increased serum levels of inflammatory cytokines (TNF-α and IL-10). Since the recognition of the importance of microbiota metabolic activity rather than their composition in the development of inflammatory disorders, e.g. IBD, the present study is the first report on the role of the SCFA system in the long lasting side effects of antibiotic treatment and its implication in IBD development. © 2019 Holota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Додано в НРАТ 2025-03-24 Закрити