Why It Is Important

The immune cells are essential for protection against pathogens yet uncontrolled immune activation can cause chronic inflammatory diseases. The interplay of the gut immune system with pathogens and commensal microbiota shapes the integrity and protection to the gut epithelial barrier and immune cells that in turn controls inflammation. Unresolved inflammation contributes to tissue injury, changes in the gut microbiota and inflammatory diseases. Despite the intense interest in developing therapeutic strategies to repair the gut damage and renew intestinal epithelial barriers, effective treatment regimens are lacking.

Our Approach

We will apply novel approaches for repairing and protecting the fragile intestine in critical clinical populations: premature infants, HIV infected adults with incomplete immune recovery, cancer patients on chemotherapy and adults with inflammatory bowel disease.

A novel combination of milk derived oligosaccharides and uniquely human Bifidobacterium species will be used that have anti-inflammatory effects on immune cells. The Program will combine our previous findings and collective expertise in human milk glycobiology and bioactive molecules, gut mucosal immunology, commensal bacteria, pediatrics/ neonatalogy, infectious diseases, cancer, clinical research, genomics and single cell analysis platforms. It will provide a dynamic and innovative platform for multidisciplinary training and mentoring of students and to generate collaborative opportunities among researchers and private sector to develop biomarkers, diagnostics and new products for protection of the fragile intestine and prevention/resolution of inflammation.

Impacts & Highlights

• Modeled lactose hydrolysis for efficiency and selectivity: towards the preservation of sialyloligosaccharides in bovine colostrum whey permeate
• Optimized enzymatic reaction conditions to produce structurally complex oligosaccharides
• Evaluated the effects of pH, transmembrane pressure, feed flow, and diafiltrations on the recovery and purity of oligosaccharides during nanofiltration
• Optimized the fermentation of monosaccharides at the laboratory and pilot scale to maximize the purity of recovered oligosaccharides during nanofiltration
• Developed a new approach to recover bovine colostrum oligosaccharides at pilot-scale: a combination of enzymatic hydrolysis, monosaccharide fermentation and nanofiltration
• Generated pilot-scale quantities of purified (monosaccharide free) oligosaccharides from bovine colostrum, human milk and goat milk
• Worked on the conversion of agricultural streams into nutraceuticals and fuel
• Optimized the use of kefir grains as an alternative methods to produce purified oligosaccharides
• Evaluated the impact of altered gut microbiota on the generation of host responses to vaccines in the non-human primate model

Team

Satya Dandekar	Professor and Chair of Medical Microbiology & Immunology
Bruce German	Professor of Food Science & Technology
Mark A. Underwood	Associate Professor and Chief of Pediatric Neonatology
David A. Mills	Professor of Viticulture & Enology
Ralph deVere White	Professor of Urology, and Assistant Dean and Director of the UC Davis Comprehensive Cancer Center
Richard Pollard	Professor and Chief of Infectious Diseases
Thomas Prindiville	Professor of Gastroenterology
Carlito B. Lebrilla	Professor of Chemistry
Daniela Barile	Assistant Professor of Food Science & Technology
Dennis Hartigan-OConnor	Assistant Professor of Microbiology & Immunology
Emanual Maverakis	Associate Professor of Dermatology
Helen Raybould	Professor of Veterinary Medicine: Anatomy, Physiology, and Cell Biology
Megan Sanctuary	Graduate Student of Nutritional Biology
Jacky Moya	Graduate Student of Nutritional Biology
Sercan Karav	Postdoc of Food Science & Technology
Juliana Mario Leite Nobrega de Moura Bell	Assistant Professor of Food Science & Technology
Irina Grishina	Graduate Student of Medical Microbiology & Immunology
Chris Gaulke	Graduate Student of Medical Microbiology & Immunology
Guochun Jiang	Project Scientist of Microbiology & Immunology
Lauren Hirao	Assistant Project Scientist of Medical Microbiology & Immunology
Clarissa Santos Rocha	Postdoc of Medical Microbiology & Immunology

For more information on this program, please contact Christine Parks ceparks@ucdavis.edu.