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Many people living with hypermobile Ehlers-Danlos syndrome (hEDS) spend years searching for answers. Severe nausea, abdominal pain, food intolerances, chronic fatigue and autonomic disorders such as postural orthostatic tachycardia syndrome (POTS) can disrupt nearly every aspect of daily life. Yet despite how common these symptoms are, researchers still do not fully understand why they occur. 

Rajan Singh, Ph.D., assistant professor of research in the Department of Physiology and Cell Biology at the University of Nevada, Reno School of Medicine (UNR Med), is developing a patient-centered research initiative to help change that.  

“For most patients, the problem is not a lack of symptoms. It's a lack of biological explanation,” Singh said. “Our responsibility is to listen carefully to patient experiences and translate them into measurable research questions.”  

Filling a critical research gap 

Research has shown that people with hEDS frequently experience gastrointestinal and autonomic symptoms, often at a level that significantly affects their quality of life. Many patients cycle through multiple specialists, repeated testing and symptom-focused treatments without finding a clear explanation for why their symptoms occur together or become so severe. 

"There are currently no proven biological markers that help explain why some patients develop severe nausea, constipation, food intolerance, pain or autonomic symptoms," Singh said. "Without that understanding, patients are often left with uncertainty and limited treatment options." 

Singh's proposed pilot study will examine the relationship between the gut microbiome, the body's chemical signals and molecules involved in communication between the digestive system, immune system and nervous system. 

By analyzing stool and blood samples alongside detailed symptom information, researchers hope to identify biological patterns that may help explain why some people experience more severe symptoms than others. 

The goal is not to create an immediate diagnostic test or treatment. Instead, the project aims to build a foundation for future research that could identify meaningful patient subgroups and guide larger studies into the causes of hEDS-related symptoms. 

Strength through collaboration 

The initiative brings together expertise from UNR Med, the Medical University of South Carolina and Mayo Clinic Rochester. 

UNR Med contributes expertise in gastrointestinal physiology, microbiome research and advanced molecular technologies. Collaborators at the Medical University of South Carolina provide clinical expertise in hEDS and access to patient cohorts, while Mayo Clinic researchers contribute strengths in gastroenterology, microbiome science and translational research. 

"This is a complex condition that affects multiple body systems," Singh said. "Answering these questions requires collaboration across institutions and specialties." 

Meeting a growing need 

Interest in understanding hEDS and related disorders is growing worldwide. Clinicians and researchers increasingly recognize the need for stronger evidence to explain patient symptoms and distinguish scientific findings from speculation or misinformation. 

"The response from the global research community shows how important this issue is," Singh said. "Patients are asking for answers, clinicians are seeing these challenges every day, and researchers recognize that much more work is needed." 

Patient engagement is a central part of the initiative. By listening to patients and understanding the symptoms that matter most to them, researchers can design studies that address real-world needs. 

The long-term vision is to establish a dedicated hEDS gut-brain research platform at UNR Med that brings together patient experiences, clinical expertise and biological research. Insights from these early studies could support future investigations into biomarkers, symptom patterns and the underlying mechanisms driving disease. 

For Singh, the goal is straightforward. 

"People living with hEDS have spent too long trying to explain symptoms that are real, complex and deeply disruptive," he said. "We may not have all the answers today, but we can build the evidence needed to find them." 

About the researcher  

An assistant professor of research in the Department of Physiology and Cell Biology, Singh’s research focuses on the gut-brain connection, gastrointestinal disorders and the microbiome. He has authored more than 50 peer-reviewed publications and earned national recognition for his contributions to neurogastroenterology and motility research, including invited presentations at Digestive Disease Week and at programs of the American Gastroenterological Association and the American Neurogastroenterology and Motility Society. 

Singh is also one of the award recipients of the Springboard Science and Research Fund, a program designed to provide crucial support to early-career biomedical scientists and researchers facing funding gaps. Funded by the Redfield Foundation, the program ensures that researchers feel supported and that their discoveries make an impact in their fields.