Summary
Professor Walters's principal interests are the Molecular and cellular function of the small intestine -- in particular how the development and differentiation of the mucosal epithelial cells affects nutrient transport. This include the effects of inflammatory diseases of the intestine causing malabsorption, such as coeliac disease and Crohn's disease, and the changes in gene expression during active disease and the repair process.
Recent research has resulted in a paradigm shift in the understanding of chronic Bile Acid Diarrhoea (also known as Bile Salt Malabsorption or Bile Acid Malabsorption). Rather than malabsorption, underproduction of the ileal hormone FGF19 results in excessive hepatic bile acid synthesis, exceeding the normal capacity for absorption. A review showed that about one-third of patients with IBS-D have BAD and this represents around 1% of the adult population.
FGF19 production in the ileum is stimulated by bile acids and this is deficient in patients with BAD. Blood levels of this hormone are low. Drugs known as FXR agonists (obeticholic acid is the first in class) are able to stimulate production of FGF19 and give symptomatic improvement.
Prof. Walters aims to increase the awareness of BAD and to develop new treatments that are well tolerated.
Selected Publications
Journal Articles
Arasaradnam RP, Brown S, Forbes A, et al., 2018, Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition, Gut, Vol:67, ISSN:0017-5749, Pages:1380-1399
Lee JM, Ong JR, Vergnes L, et al., 2018, Diet1, bile acid diarrhea, and FGF15/19: mouse model and human genetic variants, Journal of Lipid Research, Vol:59, ISSN:0022-2275, Pages:429-438
Appleby RN, Nolan JD, Johnston ID, et al., 2017, Novel associations of bile acid diarrhoea with fatty liver disease and gallstones: a cohort retrospective analysis., Bmj Open Gastroenterology, Vol:4, ISSN:2054-4774
Johnston IM, Nolan JD, Pattni SS, et al., 2016, Characterizing Factors Associated With Differences in FGF19 Blood Levels and Synthesis in Patients With Primary Bile Acid Diarrhea, American Journal of Gastroenterology, Vol:111, ISSN:1572-0241, Pages:423-432
Walters JRF, Johnston IM, Nolan JD, et al., 2015, The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid, Alimentary Pharmacology & Therapeutics, Vol:41, ISSN:0269-2813, Pages:54-64
Walters JRF, 2014, Bile acid diarrhoea and FGF19: new views on diagnosis, pathogenesis and therapy, Nature Reviews Gastroenterology & Hepatology, Vol:11, ISSN:1759-5045, Pages:426-434
Pattni SS, Brydon WG, Dew T, et al., 2013, Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention, Alimentary Pharmacology & Therapeutics, Vol:38, ISSN:0269-2813, Pages:967-976
Zhang JH, Nolan JD, Kennie SL, et al., 2013, Potent stimulation of fibroblast growth factor 19 expression in the human ileum by bile acids, American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol:304, ISSN:0193-1857, Pages:G940-G948
Pournaras DJ, Glicksman C, Vincent RP, et al., 2012, The Role of Bile After Roux-en-Y Gastric Bypass in Promoting Weight Loss and Improving Glycaemic Control, Endocrinology, Vol:153, ISSN:0013-7227, Pages:3613-3619
Walters JRF, 2010, Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder, Expert Review of Gastroenterology & Hepatology, Vol:4, ISSN:1747-4124, Pages:561-567
Akbar A, Yiangou Y, Facer P, et al., 2010, Expression of the TRPV1 receptor differs in quiescent inflammatory bowel disease with or without abdominal pain, Gut, Vol:59, ISSN:0017-5749, Pages:767-774
Walters JRF, Tasleem AM, Omer OS, et al., 2009, A New Mechanism for Bile Acid Diarrhea: Defective Feedback Inhibition of Bile Acid Biosynthesis, Clinical Gastroenterology and Hepatology, Vol:7, ISSN:1542-3565, Pages:1189-1194
Wedlake L, A'Hern R, Russell D, et al., 2009, Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome, Alimentary Pharmacology & Therapeutics, Vol:30, ISSN:0269-2813, Pages:707-717
Akbar A, Yiangou Y, Facer P, et al., 2008, Increased capsaicin receptor TRPV1-expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain, Gut, Vol:57, ISSN:0017-5749, Pages:923-929
Thomas PD, Forbes A, Green J, et al., 2003, Guidelines for the investigation of chronic diarrhoea, 2nd edition, Gut, Vol:52, ISSN:0017-5749, Pages:1-15
Moss SF, Attia L, Scholes JV, et al., 1996, Increased small intestinal apoptosis in coeliac disease, Gut, Vol:39, ISSN:0017-5749, Pages:811-817
WALTERS JRF, BANKS LM, BUTCHER GP, et al., 1995, DETECTION OF LOW BONE-MINERAL DENSITY BY DUAL-ENERGY X-RAY ABSORPTIOMETRY IN UNSUSPECTED SUBOPTIMALLY TREATED CELIAC-DISEASE, Gut, Vol:37, ISSN:0017-5749, Pages:220-224
HOWARD A, LEGON S, SPURR NK, et al., 1992, MOLECULAR-CLONING AND CHROMOSOMAL ASSIGNMENT OF HUMAN CALBINDIN-D9K, Biochemical and Biophysical Research Communications, Vol:185, ISSN:0006-291X, Pages:663-669
Books
Waters J, Walters JWJ, 2015, What's Up With Your Gut? Why You Bloat After Eating Bread and Pasta... and Other Gut Problems, ISBN:9781781610688