Golota Y. Biochemical features of intestinal barrier long-term after ceftriaxone administration

The study is dedicated to the investigation of the interconnection between metabolic activity of microbiota and biochemical indicators of the intestinal barrier integrity long-term after antibiotic ceftriaxone administration. The administration of the cephalosporin antibiotic ceftriaxone (300 mg/kg, 14 days) induced the stable downregulation of SCFAs level with preponderance of acetate and loss of propionate and butyrate. These changes were associated with decrease immunoreactivity of the FFA2 and FFA3 receptors in rats' colon mucosa. Ceftriaxone administration decreased the immunoreactivity for SMCT1 transporters of SCFA on the brush border of enterocytes, however increased the immunoreactivity for MCT1 & MCT4 transporters on the basolateral membrane of enterocytes. Even in 56 days after antibiotic withdrawal (the 72nd day of the experiment) levels of SCFAs and FFA3 were still below control value. These changes evoked a significant shift in colonic mucosal homeostasis. We found increased level of TBA-active substances, decreased the activity of SOD and catalase antioxidant enzymes after ceftriaxone injection. The disturbance of oxidant-antioxidant balance induced reduction of protein SH-groups and activation of redox-sensitive transcription factors Egr-1, Sp-1, HIF1? and ERK1/2 MAP kinase. Consequently, these changes provoked colonic mucus barrier dysfunction long-term after the antibiotic withdrawal (the 72nd day of the experiment). The total concentration of mucus glycoproteins was decreased. Moreover, we found changes in the glycosylation of mucins. Levels of hexoses and fucose were decreased, while sialation of mucus glycoproteins was increased. Similar mucosal glycosylation alterations occur during IBD development. These changes were accompanied by increased activity of рroinflammatory matrix metalloproteinase MMP-9 and decreased anti-inflammatory MMP-2 in rats colon mucosa. Mucus barrier defects at the 72nd day of the experiment were associated with increased permeability of colon epithelium measured by Evans blue permeation method. In addition, we found increased bacterial translocation to the blood. Intestinal barrier disruption long-term after the ceftriaxone withdrawal (the 72nd day of the experiment) was associated with enhanced sensitivity of rats to the iodoacetamide-induced colitis. This was manifested by an increase in the colon wet weight and an increase in the serum levels of inflammatory cytokines TNF? and IL-10.