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

PIQUERAS VA, BARRIOS B, MACCIO MARETTO L, CORREA SG.

Tucumán

Congreso; LXVII Reunión Científica Annual de la Sociedad Argentina de Inmunología.; 2019

Sociedad Argentina de Inmunología

Azithromycin is a second-generation macrolide weakly active against Gram-positive bacteria but considerably effective against Gram-negative organisms. It binds to the 50S subunit of the bacterial ribosome and inhibits protein synthesis. When administered orally is absorbed rapidly and plasma concentrations peak after 2?3 h. The impact of short-term treatment on the gut microbiota involves decrease in richness and diversity and altered taxonomic composition while long-term effects are not well known. We evaluated the effect of a 5-day azithromycin administration protocol (gavage or drinking wáter, 4 or 50 mg/kg/day) in adult C56BL6 (WT). Afterwords we collected lymph and feces (to evaluate microbiota metabolites) and isolated proximal (draining small intestine) and distal (draining colon) mesenteric lymph nodes (MLN) to evaluate CD4 and CD19 lymphoid subsets by flow cytometry. Also we evaluated the susceptibility to the antibiotic treatment in Per2ko mice (deficient in clock gene) which exhibit differences in microbiota composition and mucosal immunity. Absolute numbers of mononuclear cells/mg of tissue were similar after administration with gavage of drink water. Changes observed were more significant at 50mg/kg/day without inducing diarrhea or weight lost. 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 CD4+ lymphocytes (p