An Attenuated Salmonella enterica Serovar Typhimurium Strain and Galacto-Oligosaccharides Accelerate Clearance of Salmonella Infections in Poultry through Modifications to the Gut Microbiome

Salmonella is estimated to cause one million foodborne illnesses in the United States every year.Salmonella -contaminated poultry products are one of the major sources of salmonellosis. Given the critical role of the gut microbiota inSalmonella transmission, a manipulation of the chicken intestinal microenvironment could prevent animal colonization by the pathogen. InSalmonella , the global regulator genefnr (f umaraten itrater eduction) regulates anaerobic metabolism and is essential for adapting to the gut environment. This study tested the hypothesis that an attenuated Fnr mutant ofSalmonella enterica serovar Typhimurium (attST) or prebiotic galacto-oligosaccharides (GOS) could improve resistance to wild-typeSalmonella via modifications to the structure of the chicken gut microbiome. Intestinal samples from a total of 273 animals were collected weekly for 9 weeks to evaluate the impact of attST or prebiotic supplementation on microbial species of the cecum, duodenum, jejunum, and ileum. We next analyzed changes to the gut microbiome induced by challenging the animals with a wild-typeSalmonella serovar 4,[5],12:r:− (Nalr ) strain and determined the clearance rate of the virulent strain in the treated and control groups. Both GOS and the attenuatedSalmonella strain modified the gut microbiome but elicited alterations of different taxonomic groups. The attST produced significant increases ofAlistipes and undefinedLactobacillus , while GOS increasedChristensenellaceae andLactobacillus reuteri . The microbiome structural changes induced by both treatments resulted in a faster clearance after aSalmonella challenge.IMPORTANCE With an average annual incidence of 13.1 cases/100,000 individuals, salmonellosis has been deemed a nationally notifiable condition in the United States by the Centers for Disease Control and Prevention (CDC). Earlier studies demonstrated thatSalmonella is transmitted by a subset of animals (supershedders). The supershedder phenotype can be induced by antibiotics, ascertaining an essential role for the gut microbiota inSalmonella transmission. Consequently, modulation of the gut microbiota and modification of the intestinal microenvironment could assist in preventing animal colonization by the pathogen. Our study demonstrated that a manipulation of the chicken gut microbiota by the administration of an attenuatedSalmonella strain or prebiotic galacto-oligosaccharides (GOS) can promote resistance toSalmonella colonization via increases of beneficial microorganisms that translate into a less hospitable gut microenvironment.