PhD Study : VALGUT: Phenyl-γ-valerolactones are microbiota-derived compounds that can impact gut health

Summary

Diets rich in (poly)phenols are recognised as having beneficial roles in health and the prevention of  a wide range of chronic diseases1. Flavan-3-ols are the major class of flavonoids in the human diet, present in tea, red wine, cocoa and berries. These flavan-3-ols have limited systemic bioavailability and growing evidence indicates that it is colonic catabolites of these compounds, namely, phenyl-ᵧ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs), that exert health effects in vivo2.

Despite their presumed importance, these gut microbiota-derived compounds are not well studied in terms of their microbial catabolism nor the resultant biological activity of PVLs and PVAs2. To address this shortfall, we will use a proven ex vivo strategy already successful in identifying novel and physiological relevant (poly)phenols from berry fruits3.

We will comprehensively determine the metabolic fate of a source of dietary flavan-3-ols following human consumption in a group of ileostomy patients4 and determine the amount of dietary flavan-3-ols that would enter the colon. Using our novel ex-vivo model3, in collaboration with the University of Parma (Prof D Del Rio), we will investigate the role of the colonic microbiota in formation of phenyl- ᵧ -valerolactones (PVLs) and their related phenylvaleric acids (PVAs), using UHPLC-ESI-MSn 5, as a function of both time and metabotype6.

Ultimately this will enable determination of the impact of these gut metabolites on models of bioactivity relevant to gastrointestinal health3,7.

References

1.Del Rio D, Rodriguez-Mateos A, Spencer JP et al. (2013) Antioxid Redox Signal 18,1818-1892

2.Mena P, Bresciani L, Brindani et al. (2018) Natural Product Reportc) DOI: 10.1039/c8np00062j

3.McDougall GJ, Allwood JW, Pereira-Caro G etal (2017) Mol Nutr Food Res. 2017 Feb;61(2). doi: 10.1002/mnfr.201600327

4.McDougall GJ, Conner S, Pereira-Caro G et al.(2014). J Agric Food Chem. 2014, 30,7631-7641

5.Brindani N, Mena P, Calani L et al. (2017) Mol Nutr Food Res 61(9). doi: 10.1002/mnfr.201700077.

6.Espín JC, González-Sarrías A, Tomás-Barberán FA. (2017) Biochem Pharmacol.; 139:82-93.

7.Brown EM, Nitecki S, Pereira-Caro G, et al (2014). Biofactors., 40, 611-623

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

• Sound understanding of subject area as evidenced by a comprehensive research proposal

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

• First Class Honours (1st) Degree
• Masters at 65%
• Research project completion within taught Masters degree or MRES
• Practice-based research experience and/or dissemination
• Experience using research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• Publications - peer-reviewed
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

• Full Award: (full-time tuition fees + £19,000 (tbc))
• Part Award: (full-time tuition fees + £9,500)
• Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

• Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
• Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
• Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
• Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living