Impact of antibiotic treatment on Lactobacillus population dynamics and intestinal T cell regulatory function 3263

Abstract Description Broad-spectrum antibiotics, such as ciprofloxacin, are commonly used via the oral route to treat infections, exposing the intestinal microbiota to its effects as an unavoidable consequence. In this study, we investigated how oral ciprofloxacin treatment impacts the intestinal microbiota composition and the consequences of these shifts on immune homeostasis in the small intestine. Our results show that ciprofloxacin treatment increases IL-10 production by intraepithelial CD4 T lymphocytes (IELs), a population of T cells that reside at the epithelial cell layer of the small intestine. Analyses of the ileal microbiota by 16S rRNA sequencing showed that ciprofloxacin treatment increases the abundance of Lactobacilli. Interestingly, we not only observed an increase in Lactobacilli, but also a change in the abundance of different Lactobacillus species that persisted at least 2 weeks after the end of treatment. Ciprofloxacin treatment promoted an increase of L. reuteri and reduction of L. murinus. In vitro experiments showed that L. reuteri is more resistant to ciprofloxacin than L. murinus, what allows it to outcompete L. murinus in the presence of ciprofloxacin in competition assays. Finally, we show that an increase in L. reuteri abundance can promote IL-10 production in CD4 IELs. Our results demonstrate that oral treatment with ciprofloxacin impacts the composition of members of the microbiota promoting the overgrowth of species that modulate the intestinal immune response. Funding Sources Supported by NIH/NIAID 1F31AI183823-01; NIH/NIAID 5T32AI106699-07; NIH/NIGMS 5R25GM125598-04; NIH/NIDDK 1R01DK129950-01; NIH/NIAID 5R01AI148661-03 Topic Categories Mucosal and Regional Immunology (MUC)