Gastrointestinal Issues in Ehlers-Danlos Syndrome

GI Issues in EDS: A Comprehensive Guide

I. Introduction

Ehlers-Danlos Syndrome (EDS) is a group of heritable connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. While musculoskeletal symptoms often dominate clinical attention, gastrointestinal (GI) issues are among the most common—and most under-recognized—manifestations of EDS, especially in those with the hypermobile type (hEDS).

Individuals with EDS frequently report symptoms like bloating, abdominal pain, reflux, constipation, nausea, and early satiety, often for years before receiving a unifying diagnosis. These symptoms can significantly impair daily functioning, nutrition, and quality of life. Despite their prevalence, GI symptoms in EDS are often dismissed, misattributed to anxiety or dietary habits, or treated in isolation without addressing the underlying connective tissue disorder.

This article provides a comprehensive guide to understanding GI involvement in EDS. It synthesizes clinical research, expert opinion, and patient experience to illuminate the mechanisms behind GI symptoms in EDS, outline diagnostic and treatment strategies, and identify unmet needs in research and care.

II. Epidemiology and Prevalence

Gastrointestinal symptoms are highly prevalent among individuals with EDS, particularly those with hEDS and Hypermobility Spectrum Disorders (HSD). Studies consistently show that more than 50% of patients with hEDS report chronic GI complaints. The rates of abdominal pain, reflux, constipation, and dyspepsia are significantly higher in hEDS populations compared to matched controls.

In one large survey of patients with hEDS, 71% reported nausea, 69% reflux, 67% postprandial fullness, and 63% dysphagia. Another study found that functional GI disorders—such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation—are present in up to 75% of individuals with hEDS.

Despite this, GI manifestations are not currently included in the diagnostic criteria for hEDS. This gap contributes to delayed diagnosis and fragmented care. Raising awareness of the frequency and severity of GI issues in EDS is an essential step toward better patient outcomes.

III. Pathophysiological Mechanisms Linking EDS and GI Dysfunction

A. Connective Tissue Laxity

The structural integrity of the gastrointestinal tract depends on collagen and other connective tissue proteins. In EDS, abnormal collagen affects the tensile strength and elasticity of tissues throughout the GI system. This can lead to conditions such as visceral ptosis (organ prolapse), hiatal and inguinal hernias, rectal prolapse, and altered motility due to abnormal compliance of the bowel wall.

Connective tissue laxity may also impair the function of sphincters (e.g., the lower esophageal sphincter), contributing to reflux and esophageal dysmotility.

B. Disordered Motility

Dysmotility is common in EDS, likely due to a combination of connective tissue abnormalities, smooth muscle dysfunction, and neural signaling disruption. Delayed gastric emptying (gastroparesis) and colonic inertia are frequently reported. Symptoms may fluctuate and include nausea, bloating, early satiety, and constipation.

Small bowel dysmotility may present as pseudo-obstruction or be misdiagnosed as functional GI disorders. Motility disorders are often exacerbated by co-occurring autonomic dysfunction.

C. Visceral Hypersensitivity and Gut-Brain Axis Dysfunction

Many EDS patients meet criteria for disorders of gut-brain interaction (formerly functional GI disorders), such as IBS and functional dyspepsia. Visceral hypersensitivity, central sensitization, and altered gut-brain signaling likely contribute. Pain may be disproportionate to endoscopic or imaging findings. These findings support a broader neuroimmune model of GI dysfunction in EDS, where the nervous, immune, and digestive systems interact dynamically.

D. Autonomic and Nervous System Contributions

Autonomic dysfunction, including Postural Orthostatic Tachycardia Syndrome (POTS), is common in hEDS. Along with EDS, Autonomic Dysfunction can affect GI motility, particularly gastric and colonic transit, and may worsen symptoms like nausea, early satiety, and bloating. Autonomic testing may help in assessing the full picture.

E. Mast Cell Activation and Immune-Mediated Effects

Mast Cell Activation Syndrome (MCAS) can coexist with EDS and affect the GI system through inflammation, increased permeability, and histamine release. Symptoms include diarrhea, cramping, reflux, and food intolerances. Although causality is not always clear, MCAS should be considered when GI symptoms are refractory or fluctuate dramatically with environmental or dietary triggers.

IV. Clinical Manifestations of GI Involvement in EDS

Gastrointestinal symptoms in EDS span the entire digestive tract, often involving multiple regions simultaneously. These symptoms may mimic or overlap with functional gastrointestinal disorders, but their underlying cause is structural and systemic.

A. Upper GI Tract

• Gastroesophageal Reflux Disease (GERD): Common due to laxity of the lower esophageal sphincter. May coexist with hiatal hernia.
• Dysphagia: Difficulty swallowing can result from esophageal dysmotility or structural abnormalities.
• Gastroparesis: Delayed gastric emptying is prevalent in hEDS. An article about Gastroparesis in EDS notes that symptoms include early satiety, nausea, and bloating. Diagnosis often requires a gastric emptying study. Gastroparesis can have a profound effect on quality of life, and many celebrities have spoken out about the difficulties of living with gastroparesis.
• Nausea: Nausea is a frequent and sometimes disabling symptom in EDS.
• Functional Dyspepsia: Upper abdominal discomfort, often associated with visceral hypersensitivity and impaired accommodation of the stomach.

B. Small Intestine

• Bloating and Abdominal Pain: Common and often disproportionate to objective findings. Small intestinal dysmotility is suspected.
• Small Intestinal Bacterial Overgrowth (SIBO): May result from impaired motility. Symptoms include gas, bloating, and malabsorption. Diagnosis is usually via breath testing.
• Malabsorption Syndromes: Though less studied, some patients experience deficiencies in fat-soluble vitamins or minerals.

C. Large Intestine and Anorectal Region

• Constipation and Colonic Inertia: Very common and often severe. May require a combination of diet, medications, and pelvic floor therapy.
• Irritable Bowel Syndrome (IBS): Both constipation-predominant (IBS-C) and mixed (IBS-M) subtypes are common in EDS. Symptoms include abdominal pain, bloating, and variable stool patterns.
• Rectal Evacuation Disorders: Including dyssynergia and paradoxical contraction. Often requires biofeedback therapy.
• Rectal Prolapse and Pelvic Floor Dysfunction: Structural laxity contributes to higher rates, even in young or nulliparous individuals.

D. Rare and Severe Presentations

• Visceroptosis: Downward displacement of abdominal organs. May cause severe bloating and abdominal distension. Imaging may reveal bowel loops positioned in the pelvis.
• Intestinal Perforation or Bleeding: Particularly in vascular EDS, though rare in hEDS.
• Intestinal Obstruction or Volvulus: Can occur due to lax mesenteric attachments or visceroptosis.

V. Diagnostic Considerations

Diagnosing gastrointestinal involvement in EDS can be challenging due to overlapping symptoms with common GI conditions, normal test results, and a lack of awareness among providers.

A. Clinical Assessment

• Comprehensive history: onset, duration, and pattern of symptoms; triggers; family history of EDS or related conditions.
• Physical exam: Beighton score for hypermobility, signs of skin elasticity or scarring, abdominal tenderness or distension.
• Consider validated questionnaires for hypermobility (e.g., Five-Point Questionnaire).

B. Diagnostic Testing

• Upper GI evaluation: Endoscopy, barium swallow, gastric emptying scan (for gastroparesis).
• Lower GI evaluation: Sitz marker studies, colonic transit studies, anorectal manometry, defecography.
• Breath testing: For SIBO.
• Laboratory workup: CBC, CMP, celiac panel, vitamin/mineral levels, inflammatory markers.
• Autonomic testing: If POTS or dysautonomia is suspected.
• Allergy/immunology consult: If MCAS is suspected.

C. Red Flags and Referral Needs

• Unintended weight loss
• GI bleeding or anemia
• Severe or worsening pain
• Suspicion of vascular EDS (e.g., family history, thin translucent skin, vascular events)

A multidisciplinary approach involving GI specialists, geneticists, dietitians, and physical therapists is often essential for accurate diagnosis and effective management.

VI. Nutritional Concerns and Eating Difficulties

Patients with EDS frequently experience challenges in maintaining adequate nutrition due to GI symptoms, food intolerances, and malabsorption. These issues can lead to weight loss, nutrient deficiencies, and in severe cases, the need for enteral or parenteral nutrition. As discussed in an article published by The EDS Clinic, the popular GLP-1 weight-loss medications like Ozempic may pose additional risks for individuals with EDS.

A. Common Nutritional Challenges

• Early satiety and nausea leading to reduced intake.
• Food intolerances and restrictive diets, often self-imposed due to symptom triggers.
• Malabsorption of fat-soluble vitamins, iron, B12, and magnesium.
• Gastroparesis complicating solid food tolerance.

B. Risk of Misdiagnosis

• Patients with low BMI, restricted eating, or anxiety about food are sometimes misdiagnosed with eating disorders when symptoms are physiological in origin.
• Collaborative care with knowledgeable dietitians and psychologists is essential to distinguish between GI pathology and disordered eating.

C. Nutrition Support Strategies

• Small, frequent meals
• High-calorie liquid supplements
• Elemental or low-residue diets for severe motility or MCAS involvement
• Micronutrient monitoring and supplementation
• Feeding tubes or TPN only when absolutely necessary, with caution due to surgical risks in EDS
• Dietary approaches tailored to hEDS patients—such as low-FODMAP, low-histamine, or elemental diets—can be helpful

VII. Treatment and Management Strategies

A. General Principles

• Focus on individualized, symptom-based management.
• Treat coexisting conditions like POTS or MCAS if relevant.
• Encourage a multidisciplinary care model.

B. Pharmacologic Treatments

• Prokinetics for gastroparesis (e.g., erythromycin, domperidone in select countries)
• Laxatives and stool softeners for constipation
• Antispasmodics and neuromodulators (e.g., amitriptyline, gabapentin) for pain and visceral hypersensitivity
• Acid suppressants (PPIs or H2 blockers) for reflux
• Mast cell stabilizers and antihistamines for suspected MCAS-related symptoms

C. Non-Pharmacologic Approaches

• Pelvic floor physical therapy
• Cognitive-behavioral therapy or gut-directed hypnotherapy for functional GI symptoms
• Biofeedback for defecatory disorders

D. Surgical Considerations

• Surgery should be avoided unless absolutely necessary due to risks of poor wound healing and complications.
• When needed (e.g., for visceroptosis or severe colonic inertia), procedures should be performed by surgeons familiar with EDS.

VIII. Patient Experiences and Quality of Life

GI symptoms significantly impact quality of life, particularly when they begin early or are misattributed to psychosomatic causes. Many patients experience:

• Medical gaslighting and dismissal of symptoms
• Social isolation due to diet restrictions and fear of symptoms
• Chronic fatigue and disability from malnutrition and discomfort

Patient advocacy, education, and access to EDS-aware providers are critical components of care.

IX. Research Gaps and Future Directions

• EDS-specific GI clinical trials are lacking
• Better understanding of pathophysiology, especially in hEDS
• Biomarkers for mast cell involvement and gut dysmotility are needed
• Standardized treatment protocols should be developed
• More education for gastroenterologists and nutritionists on EDS-related GI issues

X. Conclusion

Gastrointestinal manifestations of EDS are common, complex, and frequently under-recognized. They range from mild discomfort to severe, life-altering symptoms that affect nutrition, autonomy, and emotional wellbeing. A comprehensive, multidisciplinary approach—rooted in empathy, clinical curiosity, and collaboration—can dramatically improve outcomes.

Recognition of EDS as an underlying contributor to GI dysfunction is a vital step forward in addressing these challenges. Patients deserve to be heard, believed, and supported as partners in their care.

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FAQ: Hypermobility and Bowel Problems

Can hypermobility cause bowel problems?
Yes. Hypermobility, especially in hEDS, often leads to constipation, bloating, pain, and IBS due to weakened connective tissue in the gut.

Can connective tissue disease cause bowel problems?
Yes. EDS and other connective tissue diseases can lead to reflux, constipation, malabsorption, and motility issues.

Why does hypermobility cause GI symptoms?
Loose connective tissue affects gut wall tone and muscle coordination, leading to slow motility, prolapse, and poor digestion.

Why do people with hypermobility have IBS?
They may have more sensitive nerves, altered motility, and a dysregulated nervous system—making the gut more reactive to food and stress.

What are the digestive issues in hEDS?
Symptoms include reflux, nausea, gastroparesis, bloating, constipation, and SIBO. The entire GI tract can be affected.

What are the GI issues with hypermobility?
Beyond bowel issues, hypermobile patients may also experience reflux, early satiety, dysphagia, and MCAS-related gut inflammation.

What is floppy bowel syndrome?
An informal term for gut laxity, slow motility, visceroptosis (organ sagging), and looping of the bowel.

Does hypermobility affect pooping?
Yes. It can lead to straining, incomplete evacuation, and pelvic floor dysfunction.

What are the symptoms of poor bowel muscle coordination?
Incomplete emptying, bloating, straining, and needing to use manual techniques to pass stool.

Why do I feel like I need to poop but only a little comes out?
Often caused by pelvic floor dyssynergia or incomplete evacuation from nerve-muscle discoordination.

What triggers IBS the most?
Common triggers include stress, high-FODMAP foods, hormones, and inflammation.

What foods should hypermobile people avoid?
Potential triggers include dairy, gluten, ultra-processed foods, and high-FODMAP items. Personalized diets help.

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References

1. Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know. Thwaites, P. A., Gibson, P. R., & Burgell, R. E. (2022). Journal of Gastroenterology and Hepatology, 37, 1693–1709. https://doi.org/10.1111/jgh.15927
2. Risks of Ozempic and Wegovy in Ehlers-Danlos Syndrome. EDS Clinic. https://www.eds.clinic/articles/risks-of-ozempic-and-wegovy-in-ehlers-danlos-syndrome
3. Prevalence and predictors of gastrointestinal dysmotility in patients with hypermobile Ehlers-Danlos syndrome: A tertiary care center experience. Alomari, M., Hitawala, A., Chadalavada, P., et al. (2020). Cureus, 12(4), e7881. https://doi.org/10.7759/cureus.7881
4. EDS and Gastroparesis. EDS Clinic. https://www.eds.clinic/articles/eds-and-gastroparesis
5. Higher prevalence of joint hypermobility in constipation predominant irritable bowel syndrome. Zweig, A., Schindler, V., Becker, A. S., van Maren, A., & Pohl, D. (2018). Neurogastroenterology & Motility. https://doi.org/10.1111/nmo.13353
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7. Gastrointestinal medication burden among persons with the Ehlers-Danlos syndromes. Dhingra, R., Bascom, R., Thompson, E., Francomano, C. A., & Schubart, J. R. (2021). Neurogastroenterology & Motility, 33, e14077. https://doi.org/10.1111/nmo.14077
8. Diet and Nutrition for Hypermobility EDS.  https://www.eds.clinic/articles/diet-nutrition-for-hypermobility-eds
9. Gastrointestinal disorders and gut-brain interaction in the EDS population. Abu-Farhaneh, H. S., et al. (2020). Frontiers in Neuroscience, 14, Article 820.
10. Nausea, Flare-Ups, and Triggers in Ehlers-Danlos Syndrome, MCAS, and POTS. EDS Clinic. https://www.eds.clinic/articles/nausea-flare-ups-and-triggers-in-ehlers-danlos-syndrome-mcas-and-pots
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