Preventive Antibiotic Treatment Increases Neonatal Chicks Susceptibility to Salmonella Infection Via Disrupting Gut Microbiota and Linoleic Acid Metabolism

Abstract Background: Antimicrobial agents have been widely used in animal farms to prevent and treat animal diseases. However, antimicrobial agents may change the bacterial community and increase susceptibility to the pathogenic bacteria infection. Here, we used metagenomic and metabonomic approach to investigate the effects of florfenicol (FFC) pre-treatment on colonization of Salmonella enterica serovar Enteritidis ( S . Enteritidis) in intestines of neonatal chicks through analysis of host responses, microbiota and metabolic changes. Results: We observed that FFC pre-treatment significantly increases the level of S . Enteritidis in the cecal contents, spleen and liver and also induces changes to the cecal microbiota and metabolism. Prior to S . Enteritidis infection, FFC significantly reduced the content of Lactobacillus , and significantly affected the linoleic acid metabolism pathway, including significantly reducing the levels of conjugated linoleic acid (CLA), and significantly increasing the abundance of 12,13-EpOME and 12,13-diHOME in cecum. After infection with S . Enteritidis, the abundance of Proteobacteria were significantly increased and the Salmonella -induced intestinal inflammatory responses and intestinal barrier damage were exacerbated. Supplementation with CLA could maintain intestinal integrity, reduce intestinal inflammation, and directly inhibit Salmonella growth to effectively reduce the Salmonella colonization, whereas the 12,13-diHOME through promoting intestinal inflammation and destroying the intestinal barrier function to support the Salmonella infection. Conclusions: Overall, FFC can decrease levels of Lactobacillus and CLA, and elevate cecal 12,13-diHOME concentrations in neonatal chicks and thereby increases susceptibility to Salmonella infection. This study revealed a potential health impact of antibiotics and disturbed gut microbiota and linoleic acid metabolism might be an intestinal health-impairing attribute and may contribute to Salmonella colonization.