Salmonella enterica serovar Typhimurium Temporally Modulates the Enteric Microbiota and Host Responses to Overcome Colonization Resistance in Swine

Salmonella enterica serovar Typhimurium is a prevalent incitant of enteritis in human beings and swine. It has been proposed that host defense responses incited by Salmonella allow the bacterium to overcome colonization resistance. To address this, piglets were orally inoculated with S. enterica Typhimurium DT104, and the host and microbial responses were temporally examined at acute (2 days post-inoculation [dpi]), subacute (6 dpi), and recovery (10 dpi) stages of salmonellosis. At the acute stage of disease, body temperatures were elevated, and feed consumption and weight gain were reduced. Densities of Salmonella associated with mucosa decreased over time, with higher densities of the bacterium in the ileum and the large intestine. Moreover, substantive histopathologic changes were observed as a function of time, with prominent epithelial injury and neutrophil infiltration observed at 2 dpi. Correspondingly, a variety host metrics were temporally affected in piglets with salmonellosis. The enteric microbiota was characterized using culture-independent and -dependent methods in concert, and taxon- and location-specific changes to the microbiota were observed in infected piglets. Bacteroides spp. (e.g. B. uniformis, B. fragilis), Streptococcus spp. (e.g. S. gallolyticus), and various Gammaproteobacteria were highly associated with inflamed tissues, while bacteria within the Ruminococcaceae and Veillonelaceae were mainly associated with healthy mucosa. In conclusion, the study findings showed that S. Typhimurium incited temporal and spatial modifications to the swine autochthonous microbiota, and to host defense responses, that were consistent with overcoming colonization resistance to incite salmonellosis in swine