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Experts review advancements in engineering microbes as living therapeutics

Huan Song
12/16/2020 9:43:51 AM

Research facilities at Everitt Lab
Research facilities at Everitt Lab
The human body is home to many complex microbial communities. For centuries, humans have been using microbes to treat different diseases. Scientists through the ages have been working to understand the composition and function of these communities and how they impact our health. Technological advancements now allow researchers to engineer microbes in new ways which rapidly expands their applications in medicine.  Researchers from The University of Illinois Urbana-Champaign led by bioengineering professor Shannon Sirk reviewed the latest advances, limitations and frontiers in living therapeutics. The researchers closely examined 279 journal articles. Their analysis was published in ACS Synthetic Biology

Vince Kelly, bioengineering Ph.D. candidate and the first author of this paper said, “we saw that there was a lack of a detailed, comprehensive review that fully captures what we do in the Sirk Lab. We wanted to fill that gap.” The Sirk Lab engineers commensal microbes into therapeutic delivery systems with the potential to treat a wide range of diseases. 

Professor Sirk is also the associate director of the Illinois Microbial Systems Initiative, an interdisciplinary community at the University of Illinois Urbana-Champaign that explores the impact of microbial systems on health, agriculture, energy, among other fields. 

While there are many microbiotas on different parts of the body, none are as diverse as in the gastrointestinal tract. This review provides a deep-dive into the uses and limitations of gut bacteria. Gut microbes contribute to human health in several key ways. First, gut microbes help our bodies digest food and better absorb nutrients. These microbial communities also regulate gastric immune system development and response. Microbial diversity can also be used to predict the immune status and disease progression in HIV patients who are immunocompromised. Lastly, there has been increasing evidence of a gut-brain axis that links gut health to neurological health. Examining the relationship between gut microbiota and disease like Alzheimer's is a growing field of study. 

Engineered bacteria can be used as therapeutics or prophylactics to treat a broad spectrum of health conditions including infectious diseases, metabolic diseases and cancer. Certain microbes also have the potential to be alternative delivery vehicles for vaccines. 

Living therapeutics also have the potential to be more cost-effective than biological drugs like monoclonal antibodies. These biological drugs are typically produced in mammalian cell culture, purified, formulated in the final drug and then administered through injection or an IV. “All of these steps have a cost, and those costs add up,” said Kelly. Compared with conventional drugs, living therapeutics made from modified bacteria are cheaper to grow and to deliver - orally or intranasally. 

This review covers the history of using microbes as drugs, the state of the field and future challenges and applications of these technologies.  “Hopefully this review will provide a framework to understand what we do and spark some creative new ideas both in Sirk Lab members and the microbial engineering field at large,” Kelly said