A collaborative team has received funding from the Barth Syndrome Foundation to advance research into the feeding and gastrointestinal challenges faced by individuals with Barth syndrome. The project, “Gut Microbiota and Metabolites in Barth Syndrome: Potential Mechanistic Links to Feeding and Gastrointestinal Dysfunction,” brings together expertise from physical therapy, orthopaedics, medicine, microbiome science, and genetics to explore how gut health may influence symptoms that affect daily life and long‑term well‑being.
Barth syndrome is a rare, inherited mitochondrial condition that primarily affects males and is associated with cardiac disease, muscle weakness, growth delay, and immune dysfunction. For many individuals, feeding and gastrointestinal issues are also a significant part of the condition. These challenges often begin early in life and can include food refusal, vomiting, and heightened sensitivity to smells and textures. Despite how common and impactful these symptoms can be, the biological mechanisms behind them remain poorly understood.
“I’m proud to lead a collaborative effort that reflects a collective commitment to interdisciplinary research addressing complex, real-world health challenges,” said Todd Cade, PT, PhD, FAPTA, chief of the Duke Doctor of Physical Therapy Division and principal investigator of the study. “By exploring how gut health, mitochondrial function, and feeding behaviors intersect in Barth syndrome, this work has the potential to inform more holistic, patient-centered approaches that improve function, comfort, and quality of life.”
Growing scientific evidence suggests that the gut microbiome—the diverse community of bacteria living in the digestive tract—plays an essential role in digestion, nutrient absorption, immune regulation, and inflammation. These bacteria also produce short‑chain fatty acids (SCFAs), metabolic byproducts known to influence appetite, gut motility, and inflammatory response. At the same time, emerging research points to interactions between the gut microbiome and mitochondria, the energy‑producing structures within cells that are directly affected in Barth syndrome. Understanding these interactions may provide critical insight into why feeding and digestive difficulties occur.
The research team will study gut microbiome composition and metabolic activity in individuals with Barth syndrome and compare findings with those of healthy family members. Participants will provide stool samples, along with information about diet, eating behaviors, and gastrointestinal symptoms. Researchers will analyze bacterial profiles and SCFA levels to assess whether specific patterns are associated with symptom severity or variation.
The study is centered on three guiding questions:
- Are gut bacteria different in individuals with Barth syndrome compared to healthy individuals?
- Do certain bacterial profiles relate to the severity of feeding and gastrointestinal symptoms?
- Are levels of short‑chain fatty acids altered, and do those differences help explain clinical outcomes?
This work highlights Duke’s strength in collaborative, cross‑disciplinary research. Along with Dr. Cade, the investigative team includes Stephanie Milosovic, PT, DPT, from Duke Orthopaedics; Jason Arnold, PhD, from Duke’s Departments of Molecular Genetics and Microbiology and assistant director of the Duke Microbiome Center; Katie Garman, MD, from Duke’s Department of Medicine; and Stacey Reynolds, PhD, from Virginia Commonwealth University. Together, the team integrates perspectives from research and clinical practice to address a complex and understudied aspect of a rare disease.
By deepening understanding of how gut bacteria and their metabolic products contribute to feeding and gastrointestinal challenges in Barth syndrome, the researchers hope to open new avenues for intervention. Over time, this work may support the development of targeted approaches—such as specialized dietary strategies or microbiome‑based therapies—to improve gut health and reduce symptom burden.
Ultimately, the goal is to translate scientific discovery into meaningful improvements for individuals and families living with Barth syndrome. Through collaborative research grounded in patient need, the Duke DPT Division and its partners aim to advance knowledge that supports better eating, improved growth, and greater comfort—foundations of health that extend across the lifespan.