Abstract: The molecular mechanism of idiopathic antibiotic-associated diarrhea is not clear. The third-generation cephalosporin ceftriaxone is a broad-spectrum antibiotic. Diarrhea is the main side-effect of ceftriaxone treatment. The present study tested the hypothesis that ceftriaxone-induced diarrhea is associated with shift in microbiota composition that followed by the alteration in colonic water/ion transport, 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 elective medium were evaluated.
Results: Decrease in Na⁺ and water absorption, surface mucus layer, Scnn1b and Aqp8 gene expression were associated with more severe diarrhea after 5 days-antibiotic treatment. After 14-days antibiotic treatment, a fewer number of animals with diarrhea was observed. It was accompanied with decrease of Cl^- and increased Na⁺ absorption and mucus secretion along with upregulation of gene expression of Cftr, Scnn1b, Slc9a3, Muc2, Ocln and Tjp1. These changes were accompanied by an increased number of culturable conditionally pathogenic microbiota after 5 days treatment almost returning to the control value after 14 days treatment.
Conclusion: We concluded that observed transitory antibiotic-associated diarrhea was a well-orchestrated at molecular level physiological defense response driven by shift in normal microbiota composition.