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A first-of-its-kind study of the multiple layers of the gut microbiome could reveal new therapies for improving bowel function after spinal cord injury (SCI).
This work is led by Ceren Yarar-Fisher, PhD, PT, vice chair of the Department of Research, Physical Medicine and Rehabilitation at The Ohio State University College of Medicine and director of Clinical Research, Belford Center for Spinal Cord Injury.
“This is rated as one of the highest priorities for people with SCI,” Dr. Yarar-Fisher says. “Patients face fecal incontinence and constipation. Typical modalities for treating this are not working out for people.”
The goal is to develop a supplement or nutritional intervention — or both — that improves bowel function.
Understanding the impact of gut bacterial imbalance
Dr. Yarar-Fisher’s translational research laboratory studies the pathophysiology of traumatic SCI in acute and chronic stages. She and her team develop novel nutritional and rehabilitation strategies to improve neurorecovery, metabolic and bowel function, and microbiome composition.
Constipation affects most individuals with chronic and complete SCI, especially those with tetraplegia.
After SCI, the loss of normal automatic control over body systems can cause gut mobility issues. This creates an imbalance between good and bad bacteria and is the likely cause of constipation, Dr. Yarar-Fisher says.
“Our laboratory provided the first critical evidence that individuals with chronic SCI have this bacteria imbalance more than uninjured individuals,” she says.
Her research also shows a higher amount of a family of bacteria consistent with constipation in individuals with long-standing SCI. Therefore, Dr. Yarar-Fisher believes that addressing the gut bacteria imbalance may be an option to improve or prevent constipation.
Her novel research recently won a $500,000 grant from Ohio’s Research Incentive Third Frontier, part of the state’s Third Frontier Initiative.
Part of the Ohio Department of Development, the Third Frontier is a technology-based economic development initiative. The effort works with innovative startup companies and a network of resources to transform ideas into new technology businesses.
Mining the gut microbiome
The gut microbiome holds incredible amounts of information and potential targets or biomarkers for therapeutic interventions for cancer, diabetes, neurodegenerative and other conditions.
Her lab has completed many studies to understand how SCI impacts the microbiome over time and how those changes impact one’s metabolic health.
“Metabolic dysfunction occurs because bacteria or molecules that are made by bacteria get into the circulatory system and travels to other organs, introducing other problems,” Dr. Yarar-Fisher says.
For this grant-funded study, researchers will assemble a clinically well-characterized cohort of individuals with SCI. Then they will:
- Identify post-injury changes in gut microbe populations from different intestinal sites by analyzing genomic and metagenomic changes that could be manipulated for therapeutic gain.
- Use data from the analyses to estimate how the biological functions attributed to specific gut microbiota are affected by SCI.
- Determine whether these and other changes can predict the probability or severity of bowel dysfunction.
Dr. Yarar-Fisher says the identification of these bacterial species may lead to the development of treatments such as:
- Prebiotics
- Probiotics
- Synbiotic mixtures of probiotics and prebiotics
Combined with fecal microbiome transplants, such therapies could ameliorate bowel dysfunction.
Big translation potential
The possible outcomes of this research are significant because the microbiome is far more amenable to modification in humans than other high-profile biological targets, Dr. Yarar-Fisher says.
Other applications of this research include:
- Benefits to children with SCI, which is an underserved patient population.
- An easy way to improve one’s quality of life through simply taking a supplement.
- A much shorter timeline for developing possible treatments compared with the typical 20+ years it takes to discover and create a new drug.
As the research develops at Ohio State, Dr. Yarar-Fisher hopes to open recruitment at other clinical sites in the future.
