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Table 3 Number of clusters, characteristics, and associations

From: Subtyping irritable bowel syndrome using cluster analysis: a systematic review

Study, year [reference]

Cluster’s profile

Findings

Black et al. 2021 [59]

Seven clusters in the ROME IV cohort group

1. (N = 161) Diarrhea and urgency with the low psychological burden

2. (N = 170) Lower overall GI symptom severity with the high psychological burden

3. (N = 165) Lower GI symptom severity with the low psychological burden

4. (N = 154) Diarrhea, abdominal pain, and urgency with the high psychological burden

5. (N = 31) Constipation, abdominal pain, bloating, with a high psychological burden

6. (N = 71) High several GI symptom severity with the high psychological burden

7. (N = 59) Constipation and bloating with the low psychological burden

The result was almost the same in the ROME III cohort group

Males have overall low symptoms and psychologic co-morbidities, people who have higher psychological co-morbidity suffer from a higher score in all psychological health measurements and, stool subtypes correlate with GI symptoms in each cluster

Han et al. 2019 [60]

Four clusters

1. (N = 153) Low symptoms and good QoL

2. (N = 106) Low symptoms and moderate QoL

3. (N = 38) High symptoms with diarrhea and poor QoL

4. (N = 35) High symptoms with low diarrhea and moderate QoL

Associations: gender with cluster’s memberships, college degree and paid employment with lower symptoms and higher QoL, and history of MDD with class four membership. Diarrhea/urgency symptoms are an important component of IBS symptom profiles

Lackner et al. 2013 [61]

Four clusters

1. (25%) High level of bowel dissatisfaction and pain frequency and QoL and low pain severity

2. (19%) Intermediate score of pain frequency and severity but a high score of bowel dissatisfaction

3. (18%) High score on all IBS-SSS

4. (37%) Low score in all dimensions except bowel dissatisfaction and QoL

Associations, total IBS-SSS score correlates with individual items of the IBS-SSS. Global characterization of IBS symptom severity was highest for cluster 3 patients, lowest for cluster 4 patients, and somewhat elevated for cluster 1 and 2 patients

Nevé et al. 2013 [63]

Five clusters grouped in 2 subpopulations

1. High GI symptom group

(clusters 2 + 3 + 5 N = 16)

2. Low GI

symptom group (clusters 1

 + 4 N = 26)

There is no association between exhaled H2 and CH4 and IBS clusters, a test meal containing lactulose can induce IBS symptoms and distinguish IBS from healthy controls

Eslick et al. 2004 [42]

Seven clusters

1. Diarrhea (24.7%)

2. Meal-related pain (12.1%)

3. Abdominal pain (7.9%)

4. Faucal indicators (12.6%)

5. Nausea/vomiting/weight loss (14.4%)

6. Constipation (8.8%)

7. Undifferentiated (19.5%)

Almost half of IBS patients have diarrhea or constipation and the remaining have mixed symptoms

The results show we can differentiate patients into upper and lower GI disorders

Guthrie et al. 2003 [51]

Three clusters

1. (N = 15) Low distension thresholds and diarrhea-predominant or alternating

2. (N = 62) Low distention thresholds and diarrhea-predominant or alternating, moderate prevalence of psychiatric disorders, and low rate of childhood sexual abuse

3. (N = 30) Higher distention thresholds and constipation-predominant or alternating, lower rates of psychiatric disorders, and low rates of medical consultations, sexual abuse, and interpersonal difficulties

Rectal sensitivity does not associate with sexual abuse. There is a relationship between IBS patients with low discomfort threshold and, sexual abuse, discomfort threshold, the severity of pain, psychiatric complexity, and treatment seeking

Also, there is an association between high consultation and psychiatric disorders

Ragnarsson et al. 1999 [52]

Three subgroups in both samples

1. (N = 31) Hard, varying consistency, and disturbing passage of stool

2. (N = 35) Loose stool and urgency

3. (N = 38) Normal stool and least disturbed passage

Two pain/bloating subgroups, one of them by little and the other by considerable pain and bloating. No relation was found between pain/bloating and bowel habit subgroup membership

The degree of pain and bloating does not associate with the type of bowel habit

No significant relation was found between sex and IBS subgroups

Howard Mertz et al. 1995 [57]

Three clusters

1. (N = 30) Hypersensitivity to phasic rectal distention, elevated anal pressures in both rest and stimulation phase, younger, diarrhea-predominant

2. (N = 29) Normal rectal sensitivity in phasic distention and hyposensitivity to the ramp, constipation-predominant

3. (N = 32) Hypersensitivity in phasic rectal distention, increased rectal compliance, constipation-predominant, hard stool, and severe symptoms

Longitudinal follow-up shows an association between symptom severity and changes in perception thresholds

Altered rectal perception must be a reliable biological marker in IBS

Ragnarsson et al. 1999 [53]

Three clusters were identified by cluster analysis of the pre-prandial manovolumetry

1. (N = 13) Increased anal canal pressure, and large rectal compliance, with more men than women

2. (N = 18) Decreased rectal sensitivity, with predominantly women and the oldest age range

3. (N = 19) Large fluctuation in anal canal motility, the lowest threshold for causing the recto sphincteric-inhibitory reflex, and the least prominent maximal repetitive rectal contraction

Three clusters of bowel habits

1. (N = 17) Hard stools and highly disturbed stool

passage

2. (N = 18) Loose stool and urgency

3. (N = 17) Normal consistency stool and the least disturbed stool

Two clusters of pain, bloating

1. (N = 39) With a low burden of symptoms

2. (N = 13) With a high burden of symptoms

The anorectal function does not associate with symptoms

Changes in rectal sensitivity do not correlate with symptoms

Rectal sensitivity was higher in women and rectal compliance was higher in men

Bouchoucha et al. 1999 [54]

Three clusters

1. Ultra-slow waves

2. Slow waves

3. Simple waves

Ultraslow waves are associated with high anal pressure, anal hypertonia, and dyschezia. Ultra-slow waves in IBS patients are not significantly different from healthy controls. Increased activity of anal sphincters associated with ultra-slow waves

Bouchoucha et al. 2006 [55]

Four clusters in patients

1. (N = 170 female + 61 male) Delayed colon transit time in the right colon

2. (N = 223 female + 61 male) Delayed colon transit time in the left colon

3. (N = 107 female + 50 male) Delayed in rectosigmoid area

4. (N = 58 female + 21male) With no markers in plain film

Three clusters in the control

1. (N = 27 female + 16 male) Delayed in the right colon

2. (N = 14 female + 35 male) Delayed in the left colon

3. (N = 16female + 26male) Delayed in rectosigmoid area

IBS patients are different from healthy control in colon transit time, marker distribution of retention, and diffusion coefficient

Bennet et al. 2018 [62]

Four clusters

1. (N = 7 HS + 18 patients) Having the lowest level of cytokines 2. (N = 11 HS + 105 patients) Moderate level of serum cytokines cluster

3. (N = 2 HS + 72 patients) Moderate level of serum cytokines cluster

4. (N = 0 HS + 49 patients) Having the highest level of serum cytokines

Systemic levels of immune activation cytokines are elevated in IBS patients, however, there is no strong association between immune activation and IBS symptoms. Also, systemic cytokines are not associated with comorbidities in IBS patients

Johanna Sundin et al. 2019 [56]

Two clusters in both IBS and HC

1. (N = 16 IBS + 10HC) With High MC

2. (N = 27 IBS + 10HC) With low MC

There is no association between MC numbers and location and pathophysiology of IBS, IBS symptoms, and subtypes

There is no difference between the two clusters of MC groups based on IgE serum level

Ian et al. 2014 [58]

2 clusters

1. (N = 15) A diminished diversity with a median of 44

2. (N = 22) Increased diversity with a median of 53

Microbial composition correlates with IBS and is associated with immunological alteration and low-grade inflammation

  1. MDD major depressive disorder, MC mast cell