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Porcine proliferative enteropathy remains one of the most prevalent diseases in swine herds worldwide. This disease is caused by  Lawsonia intracellularis , an intracellular bacterial pathogen that primarily colonizes the ileum. In this study, we evaluated changes to the microbiome of the ileal mucosa, ileal digesta, cecal digesta, and feces subsequent to challenge with  L. intracellularis  and to an oral live vaccine against  L. intracellularis . Given that gut homogenates have been used since 1931 to study this disease, we also characterized the microbial composition of a gut homogenate from swine infected with  L. intracellularis  that was used as challenge material. The  L. intracellularis  challenge led to a dysbiosis of the microbiome of both the small and large intestine marked by an increase of pathobionts including  Collinsella, Campylobacter, Chlamydia , and  Fusobacterium . This microbiome response could play a role in favoring  L. intracellularis  colonization and disease as well as potentially predisposing to other diseases. Vaccination altered both small and large intestine microbiome community structure and led to a significant 3.03 log 10  reduction in the amount of  L. intracellularis  shed by the challenged pigs. Vaccination also led to a significant decrease in the abundance of  Collinsella, Fusobacterium , and  Campylobacter  among other microbial changes compared with non-vaccinated and challenged animals. These results indicate that  L. intracellularis  infection is associated with broad changes to microbiome composition in both the large and small intestine, many of which can be mitigated by vaccination.

Oral Vaccination Reduces the Effects of Lawsonia intracellularis Challenge on the Swine Small and Large Intestine Microbiome