the effect of broad-spectrum antibiotic ceftriaxone on net colonic water and ion transport in vivo

Introduction: the molecular mechanism of idiopathic antibiotic-associated diarrhea is not clear. сeftriaxone, a third-generation cephalosporin, is a broad-spectrum antibiotic and diarrhea is the main side-effect of ceftriaxone treatment. the present study tested the hypothesis that ceftriaxone-induced diarrhea is associated with a shift in microbiota composition followed by the alteration in colonic water/ion transport, the expression pattern of transporters and epithelial barrier function.methods: male wistar rats were treated daily with ceftriaxone (50 mg/kg, i.m.) for 5 or 14 days. epithelial net water and ion transport (na+ , k+ , cl-) were evaluated on the 6th or 15th day respectively by isolated colonic loop perfusion technique in vivo. gene expression by rt-pcr, glycoproteins levels by pas-staining, and microbiota by culture method on the elective medium were evaluated.results: decreases in na+ and water absorption, surface mucus layer, and scnn1b and aqp8 gene expression were associated with more severe diarrhea after 5 days-antibiotic treatment. after 14-days of antibiotic treatment, fewer animals with diarrhea were observed. at the same time, there was a decrease of cl- and an increase in na+ absorption, along with increased mucus secretion and upregulation of cftr, scnn1b, slc9a3, muc2, ocln, and tjp1 gene expression. these changes were accompanied by an increase in the number of culturable conditionally pathogenic microbiota after 5 days of treatment which almost returned to the control value after 14 days of treatment.conclusion: we concluded that the observed transitory antibiotic-associated diarrhea was a well-orchestrated physiological defense response at the molecular level driven by the shift in normal microbiota composition.