Location: Animal Parasitic Diseases LaboratoryTitle: Molecular and metabolomic changes in the proximal colon of pigs infected with Trichuris suis
|BELL, NICKI - Metabolon, Inc|
|SHEA-DONOHUE, TEREZ - University Of Maryland School Of Medicine|
|KRINGEL, HELENE - University Of Copenhagen|
Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/6/2020
Publication Date: 7/31/2020
Citation: Dawson, H.D., Chen, C.T., Li, R.W., Bell, N., Shea-Donohue, T., Kringel, H., Beshah, E., Hill, D.E., Urban Jr, J.F. 2020. Molecular and metabolomic changes in the proximal colon of pigs infected with Trichuris suis. Scientific Reports. 10, 12853. https://doi.org/10.1038/s41598-020-69462-5.
Interpretive Summary: Pigs infected with whipworm, Trichuris suis, have reduced performance and health with a negative effect on productivity. The pig whipworm has also been used as a treatment for humans with inflammatory bowel diseases (IBD) because of its ability to reduce inflammation but with limited infectivity in humans. Trichuris suis induces a self-limiting host protective response in pigs that develops over several weeks with associated changes in circulating parasite specific antibodies and localized inflammation in the intestine. We used a molecular technique to evaluate the expression of numerous genes in the intestine of pigs infected with whipworm and an evaluation of changes in metabolism in the gut during the infection to better understand the features of this infection in pigs and, by extension, in humans. There was a local immune activation, and increased markers of inflammation and oxidative stress, but also several enzymes related to tissue repair and healing. There were also changes in several pathways related to fatty acids, proteins, sugars and bacterial metabolites. The number of genes that were expressed when worms persisted in the intestine was 5-fold greater than when they were expelled, and the tissue repair genes were reduced as the intestine returned to normal. This pig model provides a context to test dietary nutrients that favorably alter intestinal bacteria to improve host intestinal health in both pigs and humans exposed to Trichuris. The work is important to pig producers and scientists interested in how worm infection alters the host immune response to protect the animals but also how inflammation is reduced to diminish the intensity of the infection.
Technical Abstract: The pig whipworm Trichuris suis is important to the swine production industry because of its negative effects on pig performance and, notably, to some humans with inflammatory bowel disease (IBD) as a therapeutic agent that modulates inflammation. Protective immunity to whipworm conforms to a Th2-dependent paradigm characterized by the response to T. muris in mice; albeit similar features have also been observed in pigs infected with T. suis by measuring localized patterns of gene expression and physiology. Trichuris suis induces a self-limiting host protective response that develops over several weeks with associated changes in circulating parasite specific antibodies and localized inflammation in the cecum and proximal colon where the worms primarily reside. Infected outbred pigs appear to segregate into those with low versus high worm burden beginning around six weeks after experimental inoculation with infective eggs. The proximal colon of pigs with persistent worm infection shows a generally inflamed tissue beginning around day 21 after inoculation that is transcriptionally characterized by increased type-2 immune activation, inflammatory markers, cellular infiltration, tissue repair enzymes, pathways of oxidative stress, and altered resistance in intestinal barrier function. This is associated with metabolic changes in fatty acid profiles, antioxidant capacity and oxidative environment, biochemicals related to methylation, protein glycosylation, extracellular matrix structure, sugars, Krebs cycle intermediates, microbe-derived metabolites and altered metabolite transport. Close to 3,000 differentially regulated genes are modulated in the proximal colon of pigs with a persistent adult worm infection at around seven weeks after inoculation that is nearly 80% lower in pigs that have expelled worms as the tissue approaches a physiological normal. This model provides a context to test dietary nutrients that favorably alter the microbiome and improve host intestinal health in both pigs and humans exposed to Trichuris.