The Link Between IBS and Hypermobility Disorders

Ehlers-Danlos syndromes (EDS) describes a group of over a dozen heritable connective tissue disorders (Thwaites, 2022). Hypermobile Ehlers-Danlos syndrome (hEDS) and HSD are the most prevalent forms, affecting 80-90% of those with EDS (Thwaites, 2022). (In older literature, HSD may also be described as joint hypermobility syndrome (JHS)). hEDS/HSD affects roughly 3% of the general population, with an increased prevalence among women (Scicluna, 2022).

Despite growing awareness, both hEDS/HSD remain underdiagnosed and take over a decade to identify in many patients (Tai, 2020). The hEDS variant of EDS is the only subtype that does not have a known genetic or defined pathophysiology (Thwaites, 2022). This absence of a genetic marker means diagnosis must be made on clinical grounds alone, which further contributes to diagnosis challenges (Quigley, 2024; Aubry-Rozier, 2021).

hEDS/HSD affects many systems including the neurologic, cardiovascular, GI, and urogynaecological systems (Thwaites, 2022). Patients with hEDS/HSD frequently report symptoms such as pain, fatigue, and joint instability (Lam, 2022). The hEDS variant of EDS is most strongly linked to digestive complications and an estimated 30-96% of patients with hEDS report GI symptoms (Thwaites, 2022).

Irritable bowel syndrome (IBS), functional dyspepsia and gastroparesis are all common in the hEDS/HSD population. In fact, research suggests that up to 62% of patients with hEDS/HSD also have IBS and 73% of patients with hEDS/HSD experience constipation (Choudhary, 2021; Aubry-Rozier, 2021). Research has also shown the risk for IBS is 2.16 times greater in those with HSD/hEDS than in those without hEDS/HSD (Zloof). When evaluated for functional gastrointestinal disorders (FGIDs), 98% of those with HSD/hEDS fulfill symptom-based criteria for 1 or more Rome IV criteria for a FGID, compared with 47% of controls (P < .0001) (Lam, 2021).

Specific GI presentations vary by patient and include a diverse range of FGID symptoms. Reflux, postprandial fullness, abdominal pain, bloating, nausea, dysphagia, vomiting, diarrhea, and constipation are all common. (Harris, 2024). Other immune-mediated GI disorders, such as celiac disease (CeD), inflammatory bowel disease and eosinophilic esophagitis, have also been associated with hEDS/HSD (Quigley, 2024).

The underlying mechanisms for GI symptoms in hEDS/HSD are multifactorial. Etiologies may include visceral hypersensitivity, central sensitization, mast cell activation, small intestinal bacterial/methane overgrowth, pelvic floor dyssynergia, medication induced constipation, rectal hyposensitivity, and/or biopsychosocial factors (Harris, 2024; Silvernale, 2024).

The effect hEDS/HSD have on connective tissue means patients with hypermobility conditions often also present with autonomic dysfunction. The autonomic system regulates "fight or flight" and "rest and digest" responses, meaning this dysfunction can affect adreno-receptor hyperresponsiveness, peripheral neuropathy, connective tissue and/or blood vessel function (Do, 2021). Impairment in the balance between these responses may also be responsible for digestive dysfunction through its impact on motility, vascular circulation and/or anatomical function (eg. connective tissue laxity), among others (Quigley, 2024).

The presence of GI symptoms in patients with hEDS/HSD can impair dietary intake, lead to anxiety and fear around food and negatively impact quality of life. Nutrition plays a key role in managing symptoms and promoting overall physical and psychological health. The focus of nutrition recommendations is generally symptom-focused and must be individualized, given the variability in symptoms and underlying mechanisms behind hEDS/HSD.

While the body of evidence to guide nutrition approaches in HSD/hEDS is small, nutrition recommendations for IBS offer helpful guidance. The National Institutes for Health and Care Excellence (NICE) guidelines provide a strong foundation that can be used as a starting point for HSD/hEDS patients to manage IBS-related symptoms. The NICE guidelines’ recommendations for IBS include:

• Regular meals and avoiding long gaps between eating
• Slow, mindful eating at mealtime
• At least 8 cups of fluid per day, especially water, herbal teas or other non‑caffeinated drinks
• Avoiding excessive caffeine, alcohol and carbonation
• Limiting insoluble high fiber foods
• Keeping fresh fruit and juices to 3 portions per day or less as tolerated
• Avoiding polyols for people with loose stools
• Including soluble fiber, such as oats (NICE, 2022)

If the NICE guidelines do not provide adequate symptom relief, patients can consider the three-phased low (fermentable oligo, di, monosaccharides, and polyols) FODMAP diet (LFD) under the guidance of a GI specialist Registered Dietitian. While limited, early research suggests the LFD may be helpful in controlling IBS symptoms among those with JHS. A study compared the impact of a LFD in patients with both IBS and JHS versus controls with IBS only. When broken down by JHS and IBS sub-type, the LFD significantly improved pain, bloating, diarrhea and constipation, with the largest effects in JHS/constipation predominant IBS (IBS-C), JHS/mixed IBS and unclassified IBS (IBS-M), and JHS/diarrhea predominant IBS (IBS-D), non-JHS/IBS-C and non-JHS/IBS-M, respectively. While more studies are needed to further contextualize these findings and provide guidance on use of the LFD in patients with JHS, these data do suggest that a LFD can provide relief for IBS symptoms in the JHS/hEDS/HSD population (Fragkos, 2019).

For patients with hEDS/HSD and constipation, other nutritional strategies to trial include addition of two kiwifruit per day and gradually increasing fiber intake (with adequate increases in hydration alongside fiber increases). Both whole food sources of soluble fiber, like oats, prunes, or flaxseed, and supplemental fiber forms, such as psyllium husk or partially hydrolyzed guar gum, can be considered (Harris, 2024).

Inadequate intake and micronutrient deficiencies are also common among patients with hEDS/HSD and should be evaluated when providing nutrition therapy. Nutrition support and micronutrient supplementation may be indicated based on a patient’s status (Baeza-Velasco, 2016). Supplementation nutrition and/or vitamin and mineral supplementation can be used to improve or maintain nutrition status when symptoms have led to suboptimal oral intake, altered utilization of nutrients and/or significant weight loss (Do, 2021). For example, vitamin D and calcium supplementation may be warranted to optimize for bone health or an oral nutrition supplement can be used to ensure a patient meets their energy needs (Baeza-Velasco, 2016).

Screening for other digestive conditions is important among patients who present with chronic GI symptoms and other red flags. Several studies suggest that patients with hEDS/HSD have a higher prevalence of CeD compared to the general population (Thwaites, 2022). CeD screening should include celiac-specific serology and family history. Evaluation for inflammatory bowel diseases (IBD) may also be warranted given the higher prevalence of IBD among those with hEDS/HSD.

            Patients with hEDS/HSD also often develop disordered eating patterns. Disordered eating behaviors can be driven by fear of GI symptoms, mechanical difficulties with chewing and swallowing and/or underlying psychological factors. Nearly 38% of patients with hEDS/HSD screen positive for avoidant/restrictive food intake disorder (ARFID) (Topan, 2023). Poor nutrition can create a disordered eating cycle that is hard to break. Inadequate intake can worsen the natural history of hEDS/HSD by contributing to physical deconditioning, reduced bone mass, fatigue, and poor quality of life (Thwaites, 2022).

Disordered eating behaviors can have a direct impact on GI symptoms as well. As intake decreases GI dysfunction declines. This in turn worsens digestive symptoms and can lead to increased restriction. These consequences of disordered eating underscore the importance of screening patients for disordered eating risk and distinguishing between necessary dietary vigilance versus excessive restriction that goes beyond what is necessary to control GI symptoms. Nutrition therapy should address the physical, psycho-social and cognitive factors that may lead to restriction in order to make sure patients are able to liberalize their diets to the maximum extent possible (Topan, 2024).

The management of GI symptoms in patients with hypermobility disorders requires a nuanced and personalized approach. A multidisciplinary care team that includes a registered dietitian, psychologist, and medical specialists is critical to ensure adequate nutritional intake, minimize risk for disordered eating and prevent secondary health complications. While progress has been achieved in the last several decades, additional education among clinical providers is still needed to further increase awareness and understanding of the complex relationship between hypermobility, GI dysfunction, and the psycho-social needs of patients with hEDS/HSD.

Routine screening for GI conditions and hypermobility disorders can significantly improve diagnosis rates and the treatment path for those with hEDS/HSD. Tailored dietary interventions will continue to play a key role in controlling symptoms and promoting quality of life in this complex patient population.

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