Baylor University researcher Aaron Wright, Ph.D., has earned a $5.6 million National Institutes of Health (NIH) Director's Transformative Research Award for a project that he and collaborators hope could lead to personalized – and revolutionary – treatments for gut microbiome diseases like Irritable Bowel Syndrome (IBS), Crohn's, Ulcerative Colitis and more. Wright, a nationally recognized microbiome researcher and chemical biologist who serves as The Schofield Endowed Chair in Biomedical Science in Baylor's Department of Biology, will partner on the project with colleagues from Weill Cornell Medicine in New York.
"The NIH Director's Transformative Award is an exciting award that we're grateful to receive," Wright said.
We've proposed an idea that is out-of-the-box but has potential. If successful, it would be truly transformative. People's gut microbiomes vary greatly, and much of this field is moving toward personalized therapies. Our long-term vision is to develop personalized fecal microbiota transplantation for microbiome diseases that identify and deliver select bacteria based on the individual."
Aaron Wright, Researcher, Baylor University
Wright will serve as co-principal investigator on the project with Randy Longman, M.D., Ph.D., director of the Jill Roberts Center for Inflammatory Bowel Disease and associate professor at Weill Cornell Medicine, and Chun-Jun Guo, Ph.D., assistant professor in the Jill Roberts Center and associate professor at Weill Cornell Medicine. They will partner on the award, which is designated by the NIH for innovative but inherently risky research endeavors that have the potential to overturn existing scientific paradigms or create new ones.
"The innovative research being done by Dr. Wright into the microbiome is garnering national recognition for Baylor University in an important and emerging area of medical sciences," said Lee Nordt, Ph.D., dean of the College of Arts & Sciences. "The specific application of this project to human health has the potential to serve individuals with a number of gut diseases, and we look forward to seeing the impact of that work."
New routes to treatment
The microbiome is the collection of microorganisms found throughout the body in areas such as the gastrointestinal (GI) tract, and Wright's research focuses on the processes that take place within the gut. Wright and his team conduct research at the interface of chemistry and microbiology to observe gut health outcomes. Their approach is to synthesize and deploy activity probes to study inputs within the gut – ranging from environmental factors to diet, along with the mechanisms and processes within the gut – to uncover clues about the causes that lead to health outcomes.
Just as each person is different, their gut microbiomes are distinct based on diet and other factors. As such, "one-size-fits-all" approaches to treating IBS, Crohn's or Ulcerative Colitis likewise vary greatly in efficacy due to the uniqueness of microorganisms in each person's gut.
"If you sampled random people from around the world, such as Japan, Norway or Kenya, you'd find different population components and distributions within their gut based primarily on diet," Wright said. "If you compare them all, you'd say, 'their guts are wildly different.' And while that's true, the argument I make is that they are all capable of nearly the same functional skills, or what we call metabolic activities."
Each person, Wright said, is capable of almost all the same metabolic processes, but there are disturbances to these processes that cause disease.
"Our approach is to measure not who the cells inside the gut are, but what they are doing. Much of this discipline has been dominated by the question of 'who's there?' We're using research at the chemistry-biology interface to try to answer the question, 'Who's there, and what are they doing?'" he said.
Personalized treatments
The answer to those questions, Wright and his collaborators hope, will enable the development of personalized treatments as an outcome of this project. Fecal microbiota transplantation has long been used in hospitals to treat individuals with infections, and that approach could be used to deposit needed bacteria tailored to the individual. However, these transplantations are not tailored to individual need but are rather an entire sample that may or may not meet an individual's specific needs.
"Our interest is to look at a person with IBD or other diseases and see if we can identify specific aspects of the microbiome that are either missing or over-expressed. We're working to develop the science to isolate specific bacteria that perform an activity we care about that could be restorative," Wright said.
From there, researchers hope to develop personalized fecal microbiota transplantations that could be deposited anywhere a colonoscopy can reach.
"No longer would you be depositing an entire fecal sample," Wright envisions, "but taking a select handful of bacterial that you could transplant. That's again the long-term goal: to treat different intestinal issues through personalized therapeutics."
The award will provide approximately $5.6 million in funding to the institutions over a five-year period.
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