Study On The Interaction Between Salmonella Derby And Gut Microbiota

Salmonella Derby has become one of the top three most common Salmonella serotypes isolated from pork and diarrheal patients in China,which poses great threat to food safety and public health.Control and prevention of Salmonella contamination and infection mainly depend on antibiotics application;however,abuse of antibiotics leads to side effects such as occurrence and prevalence of antibiotic resistant and even multi-drug resistant strains.Therefore,it's urgent to develop alternatives to control Salmonella contamination and infection.Recent studies demonstrated that certain bacteria of the gut microbiota and their metabolites have dramatic effects on Salmonella colonization and infection process,positively or negatively,thus it is potential to use these bacteria for Salmonella control.However,the majority of the studies on Salmonella-microbiota interaction are based on Salmonella Typhimurium,with very limited knowledge on how Salmonella Derby interacts with the gut microbiota.Given that Salmonella Derby shows distinctly different pathogenicity,immune responses,fecal shedding patterns from Salmonella Typhimurium,it's critical to reveal the interactions between Salmonella Derby and the gut microbiota,which will lay foundation for developing novel methods of preventing Salmonella Derby.Moreover,to date,little is known whether Salmonella strains with highly conversed genomic background interact with the gut microbiota in a similar manner or not.To bridge these knowledge gaps,we selected two representative Salmonella Derby strains,14T and 14C,from our sequenced strain collections,and investigated Salmonella-gut microbiota interactions in vivo and in vitro,to identify the common and strain-specific host responses and affected gut microbiota members,and also identify the key gut microbiota members and their effects on Salmonella Derby growth and infection.The results demonstrated that Salmonella Derby 14T and 14C had no difference in term of resistant antibiotics and biochemical property;however,14C showed stronger adhesion ability to MC 38 cells.Orally administrated Salmonella Derby successfully colonized mice gut,triggered host inflammatory responses,and even overcame intestinal barrier to invade spleen and liver.Strain 14C persisted in higher population in spleen compared with 14T,while 14T triggered stronger inflammation and slowed down body weight gain process of the mice than 14C.Moreover,Salmonell a Derby 14C significantly increased the diversity of gut microbiota while 14T decreased the diversity of the gut microbiota.While 14C significantly increased the abundance of Clostridiales,14T treated mice had significantly more Bacteroidiales compared with the control at initial day of infection.At two days post infection,the diversity of gut microbiota decreased in 14C treated mice while increased in 14T treated mice;14T treatment dramatically increased the abundance of Lactobacillales and Enterobacteriaceae,while no families of gut microbiota showed significantly decreased abundance in 14C treated mice.At last day post infection,both 14T and 14C treated mice had significantly more diverse gut microbiota,and more abundant Clostridiales,but they decreased the abundance of different gut microbiota members.Overall,our results demonstrated highly similar strains 14T and 14C infection exerted distinct effects on host responses and structure of gut microbiota.Through linear discriminant effect size(LEfSe)analysis,a key member of gut microbiota that significantly responded to Salmonella Derby infection,Lactobacillus,was identified,and several Lactobacillus strains were isolated.In vit.ro antagonistic experiments demonstrated these Lactobacillus isolates inhibited the growth of tested strains affiliated with Salmonella Derby,Salmonella Typhimurium and several other common foodborn pathogens,which indicates the inhibitory effects of the Lactobacillus isolates are broad-spectrum.Cell infection assay showed Lactobacillus isolates decreased the adhesion ability of Salmonella Derby,further qRT-PCR results showed that invasion-associated genes of Salmonella Derby,including invA and sipB,were down-regulated significantly,together suggesting Lactobacillus inhibited colonization of Salmonell a Derby by down-regulating the expression level of invasion-associated genes.These results also suggested that Lactobacillus isolates have great potential in preventing and controlling Salmonella Derby contamination.Our study revealed similarities and differences of highly similar Salmonella Derby strains on host responses and structure of gut microbiota,and investigated the effects of Lactobacillus,a key member of gut microbiota,on Salmonella Derby.Our study will lay great foundation for developing a new appoach for preventing and controlling Salmonella contamination in farms and slaughterhouse.