Microbiome and Immune Response to Salmonella enterica serovar Typhimurium and Lawsonia intracellularis Infection in Swine

Abstract

Salmonella enterica is a leading cause of foodborne illness world-wide. In the US alone Salmonella is responsible for over 1 million cases of disease a year in humans and causes an estimated loss of more than 3.5 billion dollars annually. Pork is frequently associated with food borne illnesses caused by S. enterica in humans, many of which are attributed to Salmonella enterica serovar Typhimurium. Efforts to reduce the incidence of salmonellosis due to meat consumption have mainly remained ineffective. This study extends previous findings that pigs are more susceptible to colonization by Salmonella enterica when co-infected with the pathogen Lawsonia intracellularis. We determined the composition of the porcine gut microbiome in response to co-infection to determine how potential disturbances caused by L. intracellularis could favor S. Typhimurium. This analysis revealed that L. intracellularis led to a decreased abundance of Clostridium species and Clostridium butyricum in addition to other changes that may favor S. Typhimurium. We also investigated if vaccination against L. intracellularis could have an effect on the shedding S. Typhimurium and found that vaccination significantly reduced S. Typhimurium shedding in animals co-infected with L. intracellularis. To better understand the host response to L. intracellularis, we performed transcriptome analysis of infected mucosal tissue and found that infection induced a signature of genes associated with inflammation and proliferation in the gut. We then tested zinc supplementation, which is known to impact immune function, and found that zinc amino acid supplementation led to a significant reduction of lesions caused by L. intracellularis. Finally, we investigated whether co-infection of enterocytes in vitro caused increases in certain inflammatory cytokines. We found that L. intracellularis up regulated expression of IL-8 and TNFα, two pro-inflammatory cytokines crucial to the pathogenesis of S. Typhimurium infection. This research suggests that increased inflammation mediated by L. intracellularis along with changes in microbiome composition are likely responsible for enhancement of S. Typhimurium infection in swine. We have also identified that L. intracellularis vaccination and zinc amino acid complex supplementation are two promising alternatives to the use of antimicrobials in swine.