Project 1: Premature Infants (led by Dr. Mark Underwood and Dr. David Mills)

Premature infants are our most nutritionally fragile population. Infection and subsequent post-natal growth retardation has immediate adverse impacts on the developing intestine, brain and immune system. Developing and protecting the intestinal mucosa is a priority in these infants for growth. The project will establish a specimen bank for all premature infants admitted to the NICU and collect serial specimens of saliva, stool, urine, and mother’s milk for retrospective analyses of potential biomarkers of early disease. Assessment will be performed of inflammatory markers, colonized microbiota, Th17:T-regulatory cells to measure the T cell development in infants, and HMO composition in mother’s milk. We will use new microfuidic- and mass spectrometry-based platforms for small size samples. We will also work closely with our collaborator in the School of Law on bioethical considerations and health disparity issues associated with premature infants, encouraging breast milk support and collecting and storing biological samples for future research.

Project 2: HIV infected individuals (led by Dr. Satya Dandekar and Dr. Richard Pollard)

HIV targets the gut mucosal immune system within days of infection and causes severe CD4+ T cell loss and epithelial barrier disruption. Gut mucosal damage contributes to the viral persistence and chronic immune activation. Although anti-HIV combination therapy suppresses viral replication, it has been ineffective to reverse the mucosal damage and to resolve chronic inflammation. No effective adjunct therapies have been identified to restore the gut mucosal immune system. This Project will utilize the novel combination of HMO and Bifidobacterium to accelerate mucosal recovery and normalize the microbiota in HIV infected patients. We propose that it will accelerate mucosal recovery and enhance epithelial barrier integrity and will help in resolving chronic inflammation in HIV infected patients. Gut biopsies and peripheral blood samples will be evaluated for the immunologic and virologic outcomes and microbiota will be assessed.

Project 3: IBD and Cancer patients (led by Dr. Thomas Prindiville, Dr. Ralph deVere-White, and Dr. J. Bruce German)

Gut mucosal damage in patients of IBD is linked with inflammation and changes in the microbiota In cancer patients, chemotherapy has profound negative effects on the gut epithelial barriers. Opportunistic bacteria infections are a pervasive problem in cancer treatment wards throughout the country. In both diseases, the mucosal damage is attributed to slow or incomplete restoration of the mucosal barriers. Clinical trials will be designed to investigate the use of the novel “synbiotic” (i.e. specifically tailored milk prebiotic-bifidobacterial probiotic combinations) for accelerating mucosal recovery to alleviate intestinal disease.