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

Abstract

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 log10 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.

Microbiota of vaccinated and non-vaccinated clinically inconspicuous and conspicuous piglets under natural Lawsonia intracellularis infection

“…Muwonge et al (26) found the top three families Prevotellaceae, Ruminococcaceae, and Lactobacillaceae as the core microbiota in their study to be associated with changes in the threshold for shedding L. intracellularis, but not to have a major effect on the clinical outcome of the disease. Some Prevotella species were found to be decreased due to oral L. intracellularis vaccination in the present study as well as in investigations by Leite et al (12,24), who found one Prevotella species to be increased in the former study and two Prevotella species to be increased and two to be decreased in the latter study due to oral L. intracellularis vaccination. Prevotella is a genus with high genetic diversity within and between species, and certain strains may exhibit pathobiontic properties by promoting chronic inflammation in humans (56,57).…”

“…Nevertheless, the existing differences in terms of OTUs differing between the two groups (Collinsella aerofaciens, Prevotella copri, and Clostridiales) resemble previous investigations with experimental L. intracellularis challenge, that have also shown that oral vaccination against L. intracellularis shapes the gut microbiota in weaned piglets. Leite et al (12,24) who investigated the impact of an oral live vaccine against L. intracellularis (Enterisol R Ileitis) in pigs experimentally challenged with L. intracellularis were in line with results of the present study. Vaccination against L. intracellularis in dually challenged pigs (L. intracellularis and S. enterica serovar Typhimurium) also induced a significant decrease in abundance of an OTU that closely matched Collinsella aerofaciens and a significant increase in the abundance of Clostridium species (24).…”

“…Compared to vaccinated piglets, the OTU 4481613 (family Coriobacteraceae, genus Collinsella, closely matching Collinsella aerofaciens) was especially enriched in non-vaccinated clinically conspicuous animals, but also in non-vaccinated clinically inconspicuous animals. Leite et al (12,24), who observed similar results refer to this bacterium as pathobiont. Pathobionts are commensal bacteria that are typically kept at low levels within a healthy gut and do not cause problems in immune-competent hosts, but have the potential to cause harm to the host leading to inflammation and pathology (60).…”

“…Vaccination against L. intracellularis in dually challenged pigs (L. intracellularis and S. enterica serovar Typhimurium) also induced a significant decrease in abundance of an OTU that closely matched Collinsella aerofaciens and a significant increase in the abundance of Clostridium species (24). In a further investigation by Leite et al (12), vaccination led again to a significant decrease in the abundance of Collinsella, Fusobacterium, and Campylobacter among other microbial changes compared with non-vaccinated and L. intracellularis-challenged animals. The authors suggest that the intestinal pathogen challenge induces dysbiosis resulting from an increase in the number of such pathobionts and vaccination might mitigate these effects, which could contribute to the development and severity of disease (12).…”

“…In a further investigation by Leite et al (12), vaccination led again to a significant decrease in the abundance of Collinsella, Fusobacterium, and Campylobacter among other microbial changes compared with non-vaccinated and L. intracellularis-challenged animals. The authors suggest that the intestinal pathogen challenge induces dysbiosis resulting from an increase in the number of such pathobionts and vaccination might mitigate these effects, which could contribute to the development and severity of disease (12). However, it must be emphasized that both studies characterized the porcine intestinal microbiota response of pigs to an experimental L. intracellularis challenge.…”