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RVC PhD: Role of Tryptophan in the Pathogenesis and Treatment of Canine Chronic Enteropathy

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  • Full or part time
    Dr A Kathrani
    Prof D Werling
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Serum tryptophan concentrations are significantly decreased in humans with inflammatory bowel disease (IBD) and there is an anti-inflammatory effect of dietary intervention with tryptophan or tryptophan metabolites in murine and porcine models of IBD. Indeed, supplementation ameliorates clinical signs, improves weight gain and histological scores and decreases gut permeability and expression of pro-inflammatory cytokines. Furthermore, serum tryptophan concentrations are inversely correlated with serum interleukin (IL)-22 concentrations and intestinal mucosal indoleamine 2,3-dioxygenase-1 (IDO-1) expression. Serum tryptophan concentrations are also associated with the composition of faecal microbiota in humans with IBD, with faeces being enriched with Escherichia coli in patients with lower serum tryptophan concentrations.

Chronic enteropathy (CE) in dogs shares many clinical and pathophysiological features with IBD in humans, with protein-losing enteropathy (PLE) being a phenotype of this disease in dogs. Canine CE is a debilitating disease and the exact cause is unknown. One study showed that despite treatment, 50% of dogs with CE had intermittent signs with 13% requiring euthanasia due to refractory disease. Therefore, more research into the mechanism of canine CE is needed to allow for the development of adjunctive treatments that may be more effective than standard treatment alone. Interestingly, not only have we have recently shown decreased serum tryptophan concentrations in dogs with PLE, but this was also negatively correlated with duodenal IDO-1 mRNA expression in dogs with PLE.

Thus, we hypothesize that dogs with CE, with or without PLE, have decreased plasma tryptophan concentrations and altered downstream metabolites from the kynurenine and serotonin pathways leading to increased serum IL-22 concentrations compared to dogs with non-inflammatory disease. Additionally, we hypothesize that a diet with additional supplementation of tryptophan in dogs with CE, with or without PLE, may help to improve the canine chronic enteropathy activity index (CCEAI) and beneficially modulate the faecal microbiota.


- Essential Requirements -
Applicants must hold, or expected to achieve a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject.

- Desirable Requirements -
A degree in Veterinary Medicine is desirable, although not essential.

Funding Notes

This is a 3 year fully-funded studentship, open to Home/EU applicants. International students are welcome to apply but must be able to fund the difference between UK/EU and international tuition fees.

The studentship will commence October 2020.

If you are interested in applying for this position, please follow the link below. Please use your personal statement to demonstrate any previous skills or experience you have in using both qualitative and quantitative research methods.

References

1 - Nikolaus S, Schulte B, Al-Massad N, et al. Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases. Gastroenterology 2017.
2 - Gupta NK, Thaker AI, Kanuri N, et al. Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity. Inflamm Bowel Dis 2012;18:1214-1220.
3 - Kathrani A, Allenspach K, Fascetti AJ, et al. Alterations in serum amino acid concentrations in dogs with protein-losing enteropathy. Journal of Veterinary Internal Medicine 2018 May; 32(3):1026-1032



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