Salmonella enterica serovar Typhimurium is a prevalent incitant of enteritis in human beings and animals. It has been proposed that host defense responses incited by Salmonella allow the bacterium to overcome colonization resistance. Piglets (n=24) were orally inoculated with S. enterica Typhimurium DT104 or buffer alone, 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 gut 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 of host metrics were temporally affected in piglets with salmonellosis (e.g. TNFα, IFNγ, PR39, βD2, iNOS, IL8, REGIIIγ). 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 Ruminococcaceae and Veillonellaceae 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.
IMPORTANCE Limited information is available on host and enteric microbiota responses incited by Salmonella enterica Typhimurium in swine, and possible mechanisms by which the bacterium overcomes colonization resistance to incite salmonellosis. Temporal characterization of a variety of host metrics in piglets (e.g. physiologic, histopathologic, and immunologic) showed the importance of studying the progression of salmonellosis. A number of host responses integrally associated with disease development were identified. Utilization of next-generation sequence analysis to characterize the enteric microbiota was found to lack sufficient resolution; however, culture-dependent and -independent methods in combination identified taxon- and location-specific changes to bacterial communities in infected piglets. The study identified bacteria and host responses associated with salmonellosis, which will be beneficial in understanding colonization resistance and for the development of effective alternatives to antibiotics to mitigate salmonellosis.