Enrofloxacin Shifts Intestinal Microbiota and Metabolic Profiling and Hinders Recovery from Salmonella enterica subsp. enterica Serovar Typhimurium Infection in Neonatal Chickens

Enrofloxacin is an important antibiotic used for prevention and treatment of Salmonella infection in poultry in many countries. However, oral administration of enrofloxacin may lead to the alterations in the microbiota and metabolome in the chicken intestine, thereby reducing colonization resistance to the Salmonella infection. To study the effect of enrofloxacin on Salmonella in the chicken cecum, we used different concentrations of enrofloxacin to feed 1-day-old chickens, followed by oral challenge with Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium). We then explored the distribution pattern of S. Typhimurium in cecum contents in vivo and analyzed the microbial community structure of cecum contents using microbial 16S amplicon sequencing. Untargeted metabolomics was used to explore the gut metabolome on day 14. Faecalibacterium and Anaerostipes, which are closely related to the chicken intestinal metabolome, were screened using a multi-omics technique. The abundance of S. Typhimurium was significantly higher in the enrofloxacin-treated group than in the untreated group, and S. Typhimurium persisted longer. Moreover, the cecal colony structures of the three groups exhibited different characteristics, with Lactobacillus reaching its highest abundance on day 21. Notably, S. Typhimurium infection is known to affect the fecal metabolome of chickens differently. Thus, our results suggested that enrofloxacin and Salmonella infections completely altered the intestinal microbiota and metabolism of chickens. IMPORTANCE In this study, we examined the effects of S. Typhimurium infection and enrofloxacin treatment on the microbiota and metabolite synthesis in chicken cecum, in order to identify target metabolites that may promote S. Typhimurium colonization and aggravate inflammation and to evaluate the important microbiota that may be associated with these metabolites. Our findings may facilitate the use of antibiotics to prevent S. Typhimurium infection.