摘要:SummarySplenic Ly6Chighmonocytes are innate immune cells involved in the regulation of central nervous system-related diseases. Recent studies have reported the shaping of peripheral immune responses by the gut microbiome via mostly unexplored pathways. In this study, we report that a 4-day antibiotic treatment eliminates certain families of the Bacteroidetes, Firmicutes, Tenericutes, and Actinobacteria phyla in the gut and reduces the levels of multiple pattern recognition receptor (PRR) ligands in the serum. Reduction of PRR ligands was associated with reduced numbers and perturbed function of splenic Ly6Chighmonocytes, which acquired an immature phenotype producing decreased levels of inflammatory cytokines and exhibiting increased phagocytic and anti-microbial abilities. Addition of PRR ligands in antibiotic-treated mice restored the number and functions of splenic Ly6Chighmonocytes. Our data identify circulating PRR ligands as critical regulators of the splenic Ly6Chighmonocyte behavior and suggest possible intervention pathways to manipulate this crucial immune cell subset.Graphical abstractDisplay OmittedHighlights•A 4-day antibiotic treatment eliminates certain bacterial families in the gut•Gut dysbiosis is followed by reduced levels of PRR ligands in the circulation•Reduction of PRR ligands relates to perturbation of splenic Ly6Chighmonocytes•Addition of PRR ligands restores splenic Ly6Chighmonocyte numbers and functionImmunology; Microbiology; Microbiome