Proceedings of The Physiological Society

Future Physiology (Leeds, UK) (2017) Proc Physiol Soc 39, PC25

Poster Communications

The intestinal epithelial barrier dysfunction long-term after ceftriaxone administration

Y. Holota1, V. Stetska1, T. Dovbynchuk1, T. Serhiychuk1, G. Tolstanova1

1. Educational and Scientific Centre "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.

Modern medicine depends on antibiotics to protect people against infection. According to epidemiological studies increasing exposure to antibiotics is associated with increased risk of developing multiple inflammatory disorders. Impairment of the intestinal epithelial barrier integrity is an important pathophysiological factor due enhance the immune response to microbial antigens. The aim of the present study was to investigate the long-term effect of antibiotic treatment on the intestinal barrier function. Methods: Male Wistar rats (n=40, 140-160 g) were treated for 14 days with broad-spectrum antibiotic ceftriaxone (Cf) (300 mg/kg, i.m.) or vehicle; euthanized in 1, 14 or 56 days after Cf withdrawal. The study was approved by the bioethical committee of Taras Shevchenko National University of Kyiv (Protocol No 8 issued by Nov 2, 2015). The parietal microbiota was analyzed by bacteriological culture methods. The surface mucus was separated from colon epithelium with N-acetyl-1-cysteine. The total levels of mucus glycoproteins, hexoses, hexosamines, fucose and sialic acids were measured colorimetrically. Epithelial permeability was evaluated by Evans blue permeation and bacterial translocation. Results: Cf injection leads to compositional changes of parietal microbiota which progress over time. Next day after Cf withdrawal the composition of the parietal microbiota was not significantly changed. However in 56 days, we found the decreased level of lacto- and bifidobacteria 1.3 and 1.8-fold, respectively. Besides, conditionally pathogenic enterobacteria, Staphylococcus spp, Clostridium spp appeared in parietal microbiota. These changes were coincident with a decreased level of mucus glycoproteins in the colon. That was accompanied by qualitative changes in the structure of glycan part of mucins. We revealed decrease of hexoses 1.2-fold (P < 0.05) and fucose 3.1-fold (P < 0.05) levels and increase the levels of sialic acids 1.5-fold (P < 0.05) in the surface mucus of rat colon which is typical during IBD development. Cf administration didn't induce significant changes in colonic epithelial permeability day after its withdrawal. In 56 days Evans blue amount which penetrated to the blood was increased 2.7-fold (P < 0.05) in ceftriaxone-treated rats in comparison to control group. These changes were accompanied by 1.6-fold (p < 0.05) increased bacterial translocation to portal vein blood. Conclusions: Thus, Cf administration for 14 days induced changes in parietal microbiota and mucus composition long-term after antibiotic withdrawal. Antibiotic-associated increased epithelial permeability and bacterial translocation might increase susceptibility to inflammatory bowel diseases development.

Where applicable, experiments conform with Society ethical requirements