Inflammatory Bowel Diseases (IBD) are conditions characterized by inflammation that may occur throughout all, or parts, of thedigestive tract. There are two main types of IBD, ulcerative colitis and Crohn’s disease, each with very different pathologies. Despite these differences, susceptibility of both diseases is believed to be caused by changes in the microbiome. These changes are due to an individual’s genetics, or through environmental exposures, such as pollutants, prescription drugs, chronic inflammation and diet. Shifts in the microbiome cause an up-regulation and activation of mucosal immune and inflammatory pathways without sufficient regulatory responses. Successful therapeutic interventions will require a holistic approach that takes into account the molecular pathophysiology of IBD, specific clinical parameters, and both immune and nutritional status.
Multi-disciplinary study of mechanisms leading to chronic intestinal inflammation
Identification of interactions between environmental factors and different genetic loci with the microbiome
Exploration of potential of microbiome-based therapies for these complex inflammatory conditions
Should you be taking prebiotics for ulcerative colitis?
By acting as food for helpful bacteria in the gut, prebiotics can contribute to a healthier digestive system.
“Think of your gut as a garden,” says William R. DePaolo, PhD, the director of the Center for Microbiome Sciences and Therapeutics at the University of Washington School of Medicine in Seattle.
“If you want to colonize and grow something, you plant seeds. Those seeds would be the probiotics.”
— Will DePaolo for Everyday Health, 2017
Immunological & metabolic analysis of inflammatory bowel disease patients undergoing ileal resection
Scott Lee, UW GI
William DePaolo, UW CMiST
Supported by CMiST start-up funds, Cure for IBD
Environmental factors, especially nutrition & dietary components, can influence or alter the microbial landscape & its functions.
The interactions between nutrition and the microbiome are highly complex.
This is due to the plasticity and diversity of the microbiota within, and across, individuals but also the highly influential nature of diet on the microbiome. The microbiome provides mechanisms that aid in energy recovery through the breakdown of poorly digestible nutrients, such as starch and other polysaccharides. This symbiotic activity influences host metabolism and gene expression. Therefore, application of new strategies to understand how dietary factors impact microbial and host metabolism are key to unlocking the potential for therapeutic discovery.
What about probiotics?
The dynamic microbial landscape of the intestine and its impact on probiotic therapy
Denise Chac and William R DePaolo
Journal of Probiotics & Health, 2016
A diverse, symbiotic ecosystem of microbes resides in our gut, contributing to the complexity of human health. As the most microbe rich area of the human body, the gut microbiota provides a number of important physiological functions including metabolism, immunity, and protection from pathogens. Environmental factors, especially nutrition and dietary-components, can influence or even completely alter the microbial landscape and its functions. Currently, it is thought that under certain, but unknown, genetic and environmental contexts these changes can cause or exacerbate chronic inflammatory diseases. While using probiotics to treat disease seems like an easy solution, both basic and clinical data have demonstrated mixed results. Thus, it is imperative to re-examine probiotics in the complex context of both a healthy and diseased microbiome along with associated factors such as diet.
A decade of research has emphasized the importance of the microbiome on human health and disease. Capitalizing on this interaction, recent efforts have sought to create microbiome-based therapeutics using fecal microbiota transplants, probiotics, elimination strategies or prebiotics.
However, new approaches to microbiome-based therapies and a more detailed and mechanistic examination of newer technologies such as recombinant probiotics, designed microbial communities, and selective antimicrobials must be performed. Further, to effectively translate this work into the clinic, there are numerous challenges that must be understood and the development of microbiome therapeutics have yet to be tested in a comprehensive fashion.
HIV-exposed microbiome impacts
the severity of co-infection
Patricia Pavlinac, UW Global Health
William DePaolo, UW CMiST
Supported by R21, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Fundamental understanding of the forces that shape host-associated microbial communities and mediate host-bacterial interactions is essential for the rational design of microbiome therapeutics.
Bench to Bedside Initiative
To mentor a clinical fellows and increase their understanding and appreciation for the applicability of traditional bench science.
As interest in the microbiome continues to grow combined with our understanding of its importance, it is clear that we are in the middle of a biomedical research revolution as both scientists and clinicians try to understand the complexities of the relationship between microbiota and human health and disease.
As part of our mission, we hope to lead this revolution at the UW by acting as a conduit to further increase the level of communication, collaboration, and compassion between scientists and clinicians.
Our goals are to guide clinical fellows to
ask the right questions,
design sound and relevant projects to address current human diseases,
further enhance their compassion for their patients by providing them with a more comprehensive picture of patient care, and
impart a genuine enthusiasm and motivation to continue working alongside scientists as they advance in their medical careers.
By inviting clinicians to join our lab, we hope to bridge the gap between clinicians and scientists and drive research forward.
The CMiST laboratory space is currently shared with Dr. William DePaolo’s research group which occupies three laboratories on the third floor and a dedicated microscope room on the fourth floor of the K-wing in the Health Sciences Building (HSB) at the University of Washington Medical Center.
Main Laboratory (HSB K327A)
The main laboratory has eight lab benches and can comfortably support 8-15 people. The lab is designed with shared or touch down bench space for CMiST clinicians and junior faculty who may not have space of their own, but who are trying to obtain preliminary data for grants and independence.
LI-COR Odyssey Fc system
MoBio PowerLyzer 24 homogenizer
Beckman Coulter Avanti JXN-30 high speed floor centrifuge
Eppendorf and Beckman Coulter table top centrifuges
Eppendorf bench top centrifuges
Thermo Fisher -20C refrigerators
Eppendorf Innova -80C freezers
Western blot, chemi and fluorescent, gel imaging
Sterile Culture (HSB K327B)
The sterile culture room, is adjacent and can only be accessed through the main lab.
Baker biosafety cabinets
Eppendorf CO2 incubators
Eppendorf table top centrifuge
Eppendorf Innova -80C freezer
Thermo Fisher refrigerator/freezer combo
Leica inverted microscope with camera system
Leica upright microscope both with camera systems
Microscope Suite (HSB K415)
Leica LMD7 laser microdissection microscope
Leica fluorescent microscope
Biosafety Level 2 (HSB K331)
The BSL2 lab is next to the sterile culture room and is only accessible through the hallway and has a keypad lock.
Bruker MALDI-TOF Biotyper
Shell Lab Bactron900 anaerobic chamber
New Brunswick Innova shakers
Eppendorf CO2 incubator
Eppendorf -80C Innova freezer
Thermo Fischer spectrophotometer
Thermo Fisher upright incubator
Baker biosafety cabinet