GASTRO – Intestinal Health and Nutritional Research

Division of Gastroenterology, Hepatology and Nutrition

Research

Intestinal Health and Nutritional Research

The Center for Intestinal Health & Nutrition Support is committed to improving nutritional care through basic research translated into clinical practice, and is engaged in several ongoing research studies:

- The effect of different types of surgical anastomotic reconstructions on long term intestinal function and clinical status, with a specific focus on end-to-end anastomosis vs. side-to-side anastomosis
- The relationship between diet, colonic bacterial flora, and colon cancer, specifically among native Africans compared to African Americans
- The relationship between diet, colonic bacterial flora, and colon cancer, specifically among native Americans in Alaska
- Strategies to prevent central line associated blood stream infections using enhanced catheter cleaning protocols in patients requiring long-term parenteral nutrition in the home
- Strategies to rescue digestive function and nutritional status in the setting of excessive weight loss following gastric bypass surgery
- Using healthcare charge trajectories to phenotype patients on long-term parenteral support
- Prospective investigation of vitamin D and nutritional status in the long-term outcome of patients with inflammatory bowel disease (IBD; Crohn’s disease, ulcerative colitis)
- Prospective investigation of dietary fiber, fruit, fat, sugar, and emulsifiers and long-term natural history in patients with IBD
- Exploration of the interactions between pancreatic exocrine function and dietary intake, with particular reference to interventional tube feeding and intravenous feeding in the management of acute pancreatitis
- Investigation of changes in mucosal function in patients with massive intestinal loss during the 12-month post-resection adaptive period.

Investigators

David G. Binion, MD

Dr. Binion’s research focuses on defining the cellular and molecular mechanisms underlying human chronic gut inflammation and the translation of this knowledge into improved care for patients suffering from Crohn’s disease and ulcerative colitis. Current work has centered on Big Data analytics and the development and transformation of the UPMC IBD Registry, a prospective, multi-year, longitudinal natural history registry database of >3,000 consented IBD patients into a metadata platform for scientific discovery. Working in collaboration with computer scientists from the University of Pittsburgh School of Information Science, this relational database continuously curates and transforms observational clinical information from the electronic medical record (EMR) and maintains >10,000 person-years of associated metadata in a secure data warehouse. Areas of active investigation include:

Developing prognostic biomarkers of IBD severity.
Characterizing the impact of diet and nutrition on IBD natural history.
Identification of biomarker patterns to predict development of dysplasia/cancer in IBD.
Identification of predictive biomarkers to guide therapeutic selection in IBD.
Comparative effectiveness studies in IBD maintenance therapy.
Defining the impact of surgical anastomotic technique on long-term clinical outcomes in Crohn’s disease.
Use of healthcare charge data as a comprehensive phenotype.
Defining the impact of Clostridium difficile infection on IBD natural history.
Characterizing extra-intestinal manifestations including anemia and autonomic dysfunction on the natural history of IBD.
Developing clinical decision support tools to optimize IBD care and implement precision medicine.

Research Schematic

Rhonda Brand, PhD

Dr. Brand engages in mucosal research related to dermatology and gastroenterology.

David Levinthal, MD, PhD

Dr. Levinthal’s lab uses both neuroanatomical tracing and neurophysiological techniques to explore the neural basis for central nervous system influences over autonomic regulation in both health and disease. His research focuses on the neural mechanisms by which the cerebral cortex influences GI tract function. Initial studies have uncovered the surprising finding that a visceromotor map of sympathetic function is embedded within the classic cortical somatotopic map of motor function. Further work is aimed at understanding the cortical regions that influence vagal function. The goal of this effort is to use the visceral maps to guide brain stimulation as a means to influence GI tract function. This line of work will lead to the development of brain-based therapies for those with forms of severe GI dysfunction refractory to standard treatments.

Research Schematic

Stephen J.D. O'Keefe, MBBS, MD, MSc

Dr. O’Keefe performs translational research into the physiological and pathophysiological responses to feeding and nutritional deprivation. He has received NIH R01 grant support for his studies on the physiological effects of feeding on pancreatic enzyme synthesis in humans with and without disease, the optimal feeding in patients with severe acute pancreatitis, and, most recently, the role of diet, the microbiome and its metabolites in determining colon cancer risk in extreme risk Alaska Native People, high-risk African Americans (AA), and minimal risk rural South Africans (NA). His pivotal study in Nature Communications in 2015 showed that switching the diets of AA and NA (i.e., Americans were given a traditional African diet high in fiber, low in meat and fat, while Africans were given a westernized diet high in meant and fat, and low in fiber) led to profound changes in the colonic microbiome and its metabolome, associated with reciprocal changes in colonic mucosal biomarkers of cancer risk within two weeks. This supports the hypothesis that diet drives colon cancer risk and that it is largely preventable by a high fiber diet. Studies are underway in Alaska to determine whether fiber supplementation will annul the health disparity and extreme rates of colon cancer risk and mortality in Alaska Natives. Finally, Dr. O’Keefe is partnering with the University of Stellenbosch in South Africa to develop the African Microbiome Institute, which he directs, with the goal of studying the ecology of the microbiome through the Faculties of Medicine, Agrisciences, and Plant Biology, with the overarching aim of improving the health of all Africans.

Research Schematic

llustration of some of the major mechanisms whereby a high-fibre diet can prevent diseases associated with high-income lifestyles HDACi=histone deacetylase inhibitors. GPCR=G protein-coupled receptor.

Anna Evans Phillips, MD, MS

Dr. Phillips’s research interest primarily focuses on pain in chronic pancreatitis, but also includes problems related to acute pancreatitis such as pain, nutrition, and diabetes.

For clinical care, visit the UPMC Center for Intestinal Health & Nutrition Support