A

Disease A

Slug:Hypermobile_Ehlers-Danlos_Syndrome
B

Disease B

Slug:Irritable_Bowel_Syndrome
G

Causal Mechanism Graphs

Hypermobile Ehlers-Danlos Syndrome

graph LR
    Joint_instability_and_recurrent_soft_tissue_injury["Joint instability and recurrent soft-tissue injury"]
    Joint_dislocation["Joint dislocation"]
    Candidate_extracellular_matrix_remodeling_abnormalities["Candidate extracellular matrix remodeling abnormalities"]
    Sleep_disturbance["Sleep disturbance"]
    Chronic_pain["Chronic pain"]
    Arthralgia["Arthralgia"]
    Joint_hypermobility["Joint hypermobility"]
    Myofibroblast_like_fibroblast_transition["Myofibroblast-like fibroblast transition"]

    Candidate_extracellular_matrix_remodeling_abnormalities --> Myofibroblast_like_fibroblast_transition
    Joint_instability_and_recurrent_soft_tissue_injury --> Joint_dislocation
    Joint_instability_and_recurrent_soft_tissue_injury --> Chronic_pain
    Joint_instability_and_recurrent_soft_tissue_injury --> Arthralgia
    Joint_hypermobility --> Joint_instability_and_recurrent_soft_tissue_injury
    Chronic_pain --> Sleep_disturbance

    style Joint_instability_and_recurrent_soft_tissue_injury fill:#dbeafe
    style Joint_dislocation fill:#fef3c7
    style Candidate_extracellular_matrix_remodeling_abnormalities fill:#dbeafe
    style Sleep_disturbance fill:#fef3c7
    style Chronic_pain fill:#fef3c7
    style Arthralgia fill:#fef3c7
    style Joint_hypermobility fill:#fef3c7
    style Myofibroblast_like_fibroblast_transition fill:#dbeafe

Irritable Bowel Syndrome

graph LR
    Bloating["Bloating"]
    Microbiome_Dysbiosis["Microbiome Dysbiosis"]
    Abdominal_Pain["Abdominal Pain"]
    Dietary_Triggers["Dietary Triggers"]
    High_Amylose_Resistant_Starch_and_Psyllium_Blend["High-Amylose Resistant Starch and Psyllium Blend"]

    Dietary_Triggers --> Abdominal_Pain
    Dietary_Triggers --> Bloating
    High_Amylose_Resistant_Starch_and_Psyllium_Blend --> Microbiome_Dysbiosis

    style Bloating fill:#fef3c7
    style Microbiome_Dysbiosis fill:#dbeafe
    style Abdominal_Pain fill:#fef3c7
    style Dietary_Triggers fill:#dcfce7
    style High_Amylose_Resistant_Starch_and_Psyllium_Blend fill:#fce7f3
S

Association Signals

Signal 1
LITERATURE LITERATURE_ASSOCIATION UNKNOWN
Population:TriNetX research network, retrospective propensity-matched analysis (2005-2023), 59,128 matched pairs of EDS patients (excluding Marfan syndrome) versus controls.
Temporal: A before B: , B before A: , Same time:
PREVALENCE: 7.3
CI: -
p:
FDR:
IBS prevalence in the EDS cohort.
OR: 2.6
CI: 2.5 - 2.8
p: 0.001
FDR:
Odds ratio for IBS in EDS versus propensity-matched controls. Reported by the source as p < 0.001, an upper bound, not a point estimate.
PMID:41432355 (SUPPORT)
Source: HUMAN_CLINICAL
"Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR 1.5, 95% CI 1.4-1.5, p < 0.001), followed by constipation (12.4%, OR 1.8, 95% CI 1.7-1.9, p < 0.001), irritable bowel syndrome (7.3%, OR 2.6, 95% CI 2.5-2.8, p < 0.001) and gastroparesis (4.7%, OR 8.2, 95% CI 7.3-9.2, p < 0.001)."
A large propensity-matched cohort quantifies elevated IBS prevalence and odds ratio in EDS patients, alongside related GI comorbidities.
Signal 2
LITERATURE LITERATURE_ASSOCIATION UNKNOWN
Population:Cross-sectional screening of 1,998 university students (non-patient, non-clinic population); 74 met EDS-hypermobility-type criteria versus 88 without.
Temporal: A before B: , B before A: , Same time:
PREVALENCE: 41.9
CI: -
p:
FDR:
Prevalence of multiple GI symptoms in EDS-HT students versus 27.3% in non-EDS-HT students (P=.05); this is a broader "multiple GI symptoms" measure rather than a formal IBS diagnosis.
PMID:27683076 (SUPPORT)
Source: HUMAN_CLINICAL
"EDS-HT students were more likely to have multiple GI symptoms (41.9% vs 27.3% P=.05), particularly postprandial fullness (34.4% vs 15.9%, P=.01) and early satiety (32% vs 17%, P=.03)"
Demonstrates the GI-symptom association is present even in a non-patient, non-clinic-selected population, reducing the concern that the association is purely an artifact of specialty-clinic ascertainment.
H

Hypotheses

Hypothesis: connective-tissue laxity in the bowel wall and its supporting mesentery, combined with autonomic dysregulation of gut motility and visceral sensitivity (part of the broader hEDS dysautonomia phenotype), together produce the altered motility and visceral hypersensitivity characteristic of IBS. A non-patient cross-sectional study found the association between hypermobility and GI symptoms was statistically dependent on autonomic symptom burden but independent of pain and psychopathology, favoring an autonomic rather than purely psychological mechanism.
PMID:27683076 (SUPPORT)
Source: HUMAN_CLINICAL
"The association between EDS-HT and postprandial symptoms was dependent on autonomic factors but independent of pain and psychopathology."
A non-patient population study finds the GI-symptom association is statistically mediated by autonomic dysfunction rather than by pain or psychiatric comorbidity, supporting an autonomic/motility mechanism over a purely central or psychosomatic one.
PMID:27683076 (SUPPORT)
Source: HUMAN_CLINICAL
"Patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT) have increased prevalence of gastrointestinal (GI) symptoms, particularly reflux and dyspepsia."
Establishes elevated GI symptom prevalence, including reflux and dyspepsia, as a recognized hEDS feature.
Y

Raw YAML

Show YAML
name: com_Hypermobile_Ehlers-Danlos_Syndrome__Irritable_Bowel_Syndrome
creation_date: '2026-09-18T02:40:05Z'
curation_status: CANDIDATE
notes: >-
  Gastrointestinal symptoms, particularly reflux, dyspepsia, and irritable
  bowel syndrome (IBS), are among the most consistently reported hEDS
  comorbidities. A large propensity-matched cohort found IBS in 7.3% of
  EDS patients versus matched controls (OR 2.6), and a non-patient
  cross-sectional study of university students found the association between
  EDS-hypermobility type and GI symptoms (particularly postprandial fullness
  and early satiety) even outside a clinical/patient-selected population,
  with the association dependent on autonomic dysfunction rather than pain
  or psychopathology. Directionality is UNKNOWN. No ICEES KG signal exists
  for this pair: hEDS (MONDO:0007523) is not a node in the ICEES KG snapshot
  at all (confirmed while curating the hEDS-POTS comorbidity entry).

disease_a:
  slug: Hypermobile_Ehlers-Danlos_Syndrome
  preferred_term: Ehlers-Danlos syndrome, hypermobility type
  term:
    id: MONDO:0007523
    label: Ehlers-Danlos syndrome, hypermobility type

disease_b:
  slug: Irritable_Bowel_Syndrome
  preferred_term: irritable bowel syndrome
  term:
    id: MONDO:0005052
    label: irritable bowel syndrome

directionality: UNKNOWN

hypotheses:
- description: >-
    Hypothesis: connective-tissue laxity in the bowel wall and its supporting
    mesentery, combined with autonomic dysregulation of gut motility and
    visceral sensitivity (part of the broader hEDS dysautonomia phenotype),
    together produce the altered motility and visceral hypersensitivity
    characteristic of IBS. A non-patient cross-sectional study found the
    association between hypermobility and GI symptoms was statistically
    dependent on autonomic symptom burden but independent of pain and
    psychopathology, favoring an autonomic rather than purely psychological
    mechanism.
  evidence:
  - reference: PMID:27683076
    reference_title: "The association between Ehlers-Danlos syndrome-hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The association between EDS-HT and postprandial symptoms was dependent on autonomic factors but independent of pain and psychopathology."
    explanation: >-
      A non-patient population study finds the GI-symptom association is
      statistically mediated by autonomic dysfunction rather than by pain or
      psychiatric comorbidity, supporting an autonomic/motility mechanism
      over a purely central or psychosomatic one.
  - reference: PMID:27683076
    reference_title: "The association between Ehlers-Danlos syndrome-hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with Ehlers-Danlos syndrome-hypermobility type (EDS-HT) have increased prevalence of gastrointestinal (GI) symptoms, particularly reflux and dyspepsia."
    explanation: Establishes elevated GI symptom prevalence, including reflux and dyspepsia, as a recognized hEDS feature.

association_signals:
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  signal_disorder_a_id: MONDO:0007523
  signal_disorder_b_id: MONDO:0005052
  population: >-
    TriNetX research network, retrospective propensity-matched analysis
    (2005-2023), 59,128 matched pairs of EDS patients (excluding Marfan
    syndrome) versus controls.
  directionality: UNKNOWN
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 7.3
      notes: IBS prevalence in the EDS cohort.
    - metric_type: OR
      metric_value: 2.6
      metric_ci_lower: 2.5
      metric_ci_upper: 2.8
      p_value: 0.001
      notes: Odds ratio for IBS in EDS versus propensity-matched controls. Reported by the source as p < 0.001, an upper bound, not a point estimate.
    evidence:
    - reference: PMID:41432355
      reference_title: "Comprehensive Risk Profile of Gastrointestinal and Extra Articular Comorbidities in Ehlers-Danlos Syndrome: A Propensity-Matched Analysis of 118,256 Individuals."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Among GI disorders, gastroesophageal reflux disease was most common in EDS (18.4%, OR 1.5, 95% CI 1.4-1.5, p < 0.001), followed by constipation (12.4%, OR 1.8, 95% CI 1.7-1.9, p < 0.001), irritable bowel syndrome (7.3%, OR 2.6, 95% CI 2.5-2.8, p < 0.001) and gastroparesis (4.7%, OR 8.2, 95% CI 7.3-9.2, p < 0.001)."
      explanation: A large propensity-matched cohort quantifies elevated IBS prevalence and odds ratio in EDS patients, alongside related GI comorbidities.

- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  signal_disorder_a_id: MONDO:0007523
  signal_disorder_b_id: MONDO:0005052
  population: >-
    Cross-sectional screening of 1,998 university students (non-patient,
    non-clinic population); 74 met EDS-hypermobility-type criteria versus 88
    without.
  directionality: UNKNOWN
  statistics:
    metrics:
    - metric_type: PREVALENCE
      metric_value: 41.9
      notes: >-
        Prevalence of multiple GI symptoms in EDS-HT students versus 27.3% in
        non-EDS-HT students (P=.05); this is a broader "multiple GI symptoms"
        measure rather than a formal IBS diagnosis.
    evidence:
    - reference: PMID:27683076
      reference_title: "The association between Ehlers-Danlos syndrome-hypermobility type and gastrointestinal symptoms in university students: a cross-sectional study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "EDS-HT students were more likely to have multiple GI symptoms (41.9% vs 27.3% P=.05), particularly postprandial fullness (34.4% vs 15.9%, P=.01) and early satiety (32% vs 17%, P=.03)"
      explanation: >-
        Demonstrates the GI-symptom association is present even in a
        non-patient, non-clinic-selected population, reducing the concern
        that the association is purely an artifact of specialty-clinic
        ascertainment.
Source:GitHub