By Fernando L. Leite, DVM MS PhD*, University of Minnesota
Enteric diseases caused by Salmonella enterica serovar Typhimurium and Lawsonia intracellularis are prevalent in many countries worldwide. Infection by either bacterium can lead to diarrhea in the pig and can also go unnoticed in subclinical infections. Production systems should monitor and control these pathogens, as they can also lead to significant production losses.

Additionally, Salmonella Typhimurium is a significant foodborne pathogen. Interestingly, data are now available indicating that what seemed to be two independent infections may be the case of one pathogen favoring the other.

How are Lawsonia and Salmonella infections related? In a 2004 French study that followed 105 farms over time, researchers found that infection by Lawsonia was a significant risk factor for increased Salmonella shedding by growing pigs. This wasn’t the first indication that these two pathogens may favor each other. In fact, Salmonella was at one time postulated to be the cause of ileitis. When veterinary pathologists at Iowa State University described ileitis for the first time in 1931, they found Salmonella in diseased pigs and hypothesized it could be contributing to disease. We now know that Lawsonia intracellularis is the causative agent of ileitis. However, Lawsonia seems to cause disease much more efficiently when other microbes are present.

Scientists from the University of Edinburgh have reported in experiments that pigs with very few bacteria present in the gut did not develop disease when infected with Lawsonia, while animals with a normal gut microbiota did. This suggests that the presence of Lawsonia alone doesn’t seem to cause ileitis, as it needs other microbes in the gut to be able to cause disease. This demonstrates that Lawsonia intracellularis interacts with other microorganisms in the gut.

So, how could Lawsonia favor Salmonella infection? There are several possible mechanisms for this. Recently, substantial data have been generated that suggests the gut microbiome (the community of bacteria in the gut) has a large impact on health and disease. Recently, at the University of Minnesota, we investigated if the gut microbiome could be involved in how Salmonella is impacted by Lawsonia. Additionally, we assessed a commercially available live attenuated vaccine to determine if vaccination against Lawsonia could impact Salmonella infection. The data suggested that Lawsonia infection significantly altered the gut microbiome. We also found that animals that were vaccinated against Lawsonia had a very different microbiome response than the non-vaccinated animals. When we investigated Salmonella shedding in animals co-infected with Lawsonia, we observed that animals vaccinated against Lawsonia shed significantly less (around 100 times less) Salmonella than the non-vaccinates. These vaccinated animals had an increased amount of beneficial microbes in their gut including Clostridium butyricum. C. butyricum is known to produce large amounts of butyrate, a short chain fatty acid which can hamper Salmonella infection. Overall this research demonstrated that the gut microbiome could be involved in the favoring of one pathogen by another.

It is also possible that the host response and lesions due to Lawsonia infection may enhance Salmonella infection. One of the major characteristics of Lawsonia infection is the decrease of mucin-producing goblet cells in lesions. Mucin is a significant barrier in the gut to invading pathogens. With decreased mucin production, Salmonella may have easier access to the intestinal lining, thereby potentially facilitating infection. Salmonella is also known for inducing inflammation to establish itself in the gut.

At the University of Minnesota, we have recently investigated the possibility that the presence of Lawsonia could increase the inflammation that favors Salmonella colonization. We measured the expression of inflammatory cytokines by intestinal cells infected with either Salmonella or Lawsonia, or in co-infection. We found that the co-infected cells expressed significantly more inflammatory cytokines than those that were singly infected. Of particular interest was that the increase of inflammatory cytokines in co-infection was much greater when compared to Lawsonia infection alone, as opposed to Salmonella infection alone. This indicates that not only does Lawsonia have a significant impact on Salmonella, but that Salmonella could also have a significant impact on Lawsonia infection.

In the future, it will be interesting to investigate if preventing Salmonella with vaccination might have an impact on Lawsonia infection.

Recent and past research has shown that Lawsonia and Salmonella like to share the gut and favor each other when infecting the pig. This brings to light the importance of understanding the status of both pathogens in a herd and striving to control both Lawsonia and Salmonella to increase intestinal health, instead of focusing on each pathogen individually. Current research focusing on gut health and its impacts on immunity may assist us in more fully understanding this complex relationship and finding solutions to reduce production losses.

* Presently technical manager at Boehringer Ingelheim Animal Health