Compartmentalization of the effect of acute administration of azithromycin in mice with altered biological clock

San Martín de Tucuman

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

Azithromycin is a second-generation macrolide with broad action against many Gram-positive and Gram-negative bacteria. It binds to the 50S subunit of the bacterial ribosome and inhibits protein synthesis. After oral administration is absorbed rapidly and widely distributed in tissues, mainly concentrated within phagocytes and fibroblasts. The impact of short-term treatment on the gut microbiota involves decrease in richness, diversity and taxonomic composition while long-term effects are unknown. We evaluated the effect of a 5-day azithromycin administration (4 or 50 mg/kg/day) by gavage or in drinking water, in adult C56BL6 (WT). Afterwards we collected lymph and feces (to evaluate microbiota metabolites), proximal and distal mesenteric lymph nodes (MLN) (draining small intestine and colon respectively) to evaluate CD3, CD4, CD8 and CD19 lymphoid subsets by flow cytometry. Also we evaluated the susceptibility to azithromycin in Per2ko mice (deficient in clock gene) which exhibit differences in microbiota and mucosal immunity. Absolute numbers and frequency of mononuclear cells were similar after administration with gavage or drinking water. Changes were more significant at 50mg/kg/day without inducing diarrhea, weight lost or colon shortening. Per2ko mice showed higher susceptibility to azithromycin administration than WT; interestingly, whereas in proximal MLN no differences were found in lymphoid subsets evaluated significant changes were observed in absolute number of CD3+CD4+ lymphocytes (p<0.01) and frequency of CD19+B cells (p<0.05) in distal MLN. These results represent our first evidence of the compartmentalization of the effect of a widely used antibiotic in the intestinal homeostasis after in acute administration.