Ivermectin-induced bacterial gut dysbiosis does not increase susceptibility to Pseudomonas aeruginosa lung infection but exacerbates liver damage

Abstract

Excessive use of medications, including the antiparasitic drug ivermectin, can lead to bacterial gut dysbiosis, an imbalance in the intestinal microbiome, which in turn may increase or decrease susceptibility to infectious processes. To better understand the effects of continuous ivermectin usage on the gut bacterial community, C57BL/6 isogenic mice were treated by gavage with ivermectin or saline. Ivermectin-induced bacterial gut dysbiosis is characterized by a decrease in Bacteroidetes, Firmicutes, Proteobacteria and Tenericutes and an increase in species of the phylum Verrucomicrobia. A pro-inflammatory immunostimulatory caecal content, as well as disruption of caecal tissue organization and liver tissue damage, was observed in mice with gut dysbiosis. However, ivermectin-induced gut dysbiosis did not lead to acute susceptibility to Pseudomonas aeruginosa lung infection: infected mice with and without gut dysbiosis showed similar rates of recovery of viable bacteria in organs, histopathology and differential cytokine expression in the lung. Therefore, an extension of liver damage was observed in ivermectin-treated and P. aeruginosa-infected mice, which was exacerbated by infection.