name: Irritable Bowel Syndrome
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Gastrointestinal Disease
disease_term:
preferred_term: irritable bowel syndrome
term:
id: MONDO:0005052
label: irritable bowel syndrome
pathophysiology:
- name: Visceral Hypersensitivity
description: >
Enhanced perception of normal gut sensations leads to pain and
discomfort. Lowered pain thresholds in response to balloon
distension. Central sensitization contributes.
biological_processes:
- preferred_term: Pain Perception
term:
id: GO:0048265
label: response to pain
evidence:
- reference: PMID:18252749
supports: SUPPORT
snippet: "A significant 3.5-fold increase in median numbers of TRPV1-immunoreactive
fibres was found in biopsies from IBS patients compared with controls (p<0.0001)."
explanation: TRPV1-expressing sensory nerve fibers are significantly
increased in IBS, providing a molecular basis for visceral
hypersensitivity.
- reference: PMID:18252749
supports: SUPPORT
snippet: "In multivariate regression analysis, only TRPV1-immuno-reactive fibres
(p = 0.005) and mast cells (p = 0.008) were significantly related to the abdominal
pain score."
explanation: TRPV1 nerve fiber density directly correlates with abdominal
pain severity in IBS patients.
- reference: PMID:17241857
supports: SUPPORT
snippet: "Mediators from IBS patients, but not controls, markedly enhanced the
firing of mesenteric nerves (14.7 +/- 3.2 imp/sec vs 2.8 +/- 1.5 imp/sec; P
< .05) and stimulated mobilization of Ca(2+) in dorsal root ganglia neurons
(29% +/- 4% vs 11% +/- 4%; P < .05)."
explanation: Mucosal mediators from IBS patients directly excite visceral
sensory neurons, demonstrating a mechanism for visceral hypersensitivity.
- reference: PMID:17241857
supports: SUPPORT
snippet: "On average, 64% of dorsal root ganglia responsive to mediators were
capsaicin-sensitive, known to mediate nociception."
explanation: The majority of sensory neurons activated by IBS mucosal
mediators are nociceptive, explaining the pain phenotype.
- name: Gut Dysmotility
description: >
Altered intestinal motility patterns with either accelerated
(diarrhea-predominant) or delayed (constipation-predominant)
transit. Abnormal colonic contractions.
biological_processes:
- preferred_term: Gut Motility
term:
id: GO:0030432
label: peristalsis
evidence:
- reference: PMID:15100164
supports: SUPPORT
snippet: "5-HT release from enterochromaffin (EC) cells initiates peristaltic,
secretory, vasodilatory, vagal and nociceptive reflexes."
explanation: Serotonin from enterochromaffin cells is a key regulator of
intestinal motility and peristaltic reflexes.
- reference: PMID:15100164
supports: SUPPORT
snippet: "5-HT directly and indirectly affects intestinal motor and secretory
function and abnormalities may lead to either constipation or diarrhea."
explanation: Dysregulated serotonin signaling can account for both IBS-D and
IBS-C subtypes through effects on motility.
- name: Gut-Brain Axis Dysfunction
description: >
Bidirectional communication between gut and brain is disrupted.
Stress and psychological factors modulate gut function through
autonomic and neuroendocrine pathways.
biological_processes:
- preferred_term: Nervous System Process
term:
id: GO:0050877
label: nervous system process
evidence:
- reference: PMID:37048642
supports: SUPPORT
snippet: "Although the pathophysiology of IBS has not been fully elucidated, it
involves dysregulation of communication between the brain and gut (brain-gut
axis) which is associated with alterations in intestinal motility, gut permeability,
visceral hypersensitivity and gut microbiota composition."
explanation: The gut-brain axis is a central organizing principle in IBS
pathophysiology, integrating multiple dysfunctional mechanisms.
- reference: PMID:15100164
supports: SUPPORT
snippet: "Ongoing, bidirectional brain-gut interactions involving 5-HT pathways
occur that significantly influence the effector systems."
explanation: Serotonin pathways mediate bidirectional brain-gut
communication in IBS.
- name: Intestinal Barrier Dysfunction
description: >
Increased intestinal permeability (leaky gut) allows translocation
of luminal antigens, triggering low-grade immune activation.
evidence:
- reference: PMID:17593135
supports: SUPPORT
snippet: "While a subgroup of patients with IBS appears to have evidence of increased
intestinal permeability, improvements in the methods and validation are key
to further research in this field in order to better understand intestinal barrier
functions in IBS."
explanation: A subset of IBS patients demonstrate measurable increases in
intestinal permeability, though the exact prevalence varies by
methodology.
- reference: PMID:19595511
supports: SUPPORT
snippet: "Approximately 39% of diarrhea-predominant IBS patients had increased
intestinal membrane permeability as measured by the lactulose/mannitol ratio."
explanation: Nearly 40% of IBS-D patients show objective evidence of barrier
dysfunction using validated permeability testing.
- reference: PMID:19595511
supports: SUPPORT
snippet: "A subset of D-IBS patients had increased intestinal membrane permeability
that was associated with an increased FBDSI score and increased hypersensitivity
to visceral and thermal nociceptive pain stimuli."
explanation: Barrier dysfunction in IBS-D correlates with more severe
symptoms and heightened visceral sensitivity, linking permeability to
clinical phenotype.
- name: Immune Activation and Mast Cell Degranulation
description: >
Low-grade mucosal immune activation with increased mast cell density
and degranulation near enteric nerves. Mast cell mediators including
histamine and tryptase excite visceral sensory neurons, contributing
to pain and hypersensitivity.
biological_processes:
- preferred_term: Mast Cell Activation
term:
id: GO:0045576
label: mast cell activation
evidence:
- reference: PMID:17241857
supports: SUPPORT
snippet: "IBS-dependent nerve firing and Ca(2+) mobilization were correlated with
the area of the colonic lamina propria occupied by mast cells (r = 0.74; P <
.01, and r = 0.78; P < .01, respectively)."
explanation: Mast cell density directly correlates with sensory neuron
activation in IBS, establishing a quantitative relationship.
- reference: PMID:17241857
supports: SUPPORT
snippet: "Mucosal mast cell mediators from IBS patients excite rat nociceptive
visceral sensory nerves. These results provide new insights into the mechanism
underlying visceral hypersensitivity in IBS."
explanation: Mast cell mediators from IBS patients directly activate
nociceptive neurons, providing a mechanistic link to pain.
- reference: PMID:18252749
supports: SUPPORT
snippet: "Substance P-immunoreactive fibres (p = 0.01), total nerve fibres (PGP9.5)
(p = 0.002), mast cells (c-kit) (p = 0.02) and lymphocytes (CD3) (p = 0.03)
were also significantly increased in the IBS group."
explanation: Both mast cells and immune cells are increased in IBS mucosa,
indicating low-grade immune activation.
- name: Microbiome Dysbiosis
description: >
Altered composition and function of gut microbiota may contribute
to symptoms. Post-infectious IBS follows gastroenteritis in
some patients.
biological_processes:
- preferred_term: Host-Microbiome Interaction
term:
id: GO:0044003
label: modification by symbiont of host morphology or physiology
evidence:
- reference: PMID:37048642
supports: SUPPORT
snippet: "It has a prevalence of 10 to 25% in the United States and has a high
disease burden, as evidenced by reduced quality of life, decreased work productivity
and increased healthcare utilization and costs."
explanation: IBS is a common disorder with substantial public health impact,
emphasizing the importance of understanding pathophysiological mechanisms
including microbiome alterations.
phenotypes:
- name: Abdominal Pain
category: Gastrointestinal
frequency: VERY_FREQUENT
diagnostic: true
notes: Related to defecation
phenotype_term:
preferred_term: Abdominal Pain
term:
id: HP:0002027
label: Abdominal pain
evidence:
- reference: PMID:18252749
supports: SUPPORT
snippet: "Increased TRPV1 nerve fibres are observed in IBS, together with a low-grade
inflammatory response. The increased TRPV1 nerve fibres may contribute to visceral
hypersensitivity and pain in IBS, and provide a novel therapeutic target."
explanation: TRPV1-expressing nerve fibers are increased in IBS and directly
linked to abdominal pain severity.
- reference: PMID:17241857
supports: SUPPORT
snippet: "IBS-dependent excitation of dorsal root ganglia was inhibited by histamine
H(1) receptor blockade and serine protease inactivation (inhibition of 51.7%;
P < .05 and 74.5%; P < .05; respectively)."
explanation: Mast cell mediators, particularly histamine and proteases,
directly excite nociceptive neurons to produce abdominal pain in IBS.
- name: Altered Bowel Habits
category: Gastrointestinal
frequency: VERY_FREQUENT
diagnostic: true
phenotype_term:
preferred_term: Abnormal Stool Pattern
term:
id: HP:0025085
label: Bloody diarrhea
- name: Bloating
category: Gastrointestinal
frequency: VERY_FREQUENT
phenotype_term:
preferred_term: Abdominal Distention
term:
id: HP:0003270
label: Abdominal distention
- name: Constipation
category: Gastrointestinal
frequency: FREQUENT
notes: IBS-C subtype
phenotype_term:
preferred_term: Constipation
term:
id: HP:0002019
label: Constipation
- name: Diarrhea
category: Gastrointestinal
frequency: FREQUENT
notes: IBS-D subtype
phenotype_term:
preferred_term: Diarrhea
term:
id: HP:0002014
label: Diarrhea
evidence:
- reference: PMID:19595511
supports: SUPPORT
snippet: "Approximately 39% of diarrhea-predominant IBS patients had increased
intestinal membrane permeability as measured by the lactulose/mannitol ratio."
explanation: Increased intestinal permeability is present in a substantial
proportion of IBS-D patients and may contribute to diarrheal symptoms.
- reference: PMID:15100164
supports: SUPPORT
snippet: "5-HT directly and indirectly affects intestinal motor and secretory
function and abnormalities may lead to either constipation or diarrhea."
explanation: Dysregulated serotonin signaling affects secretion and
motility, contributing to diarrhea in IBS-D.
- name: Fatigue
category: Systemic
frequency: FREQUENT
phenotype_term:
preferred_term: Fatigue
term:
id: HP:0012378
label: Fatigue
genetic:
- name: HTR3E
association: Risk Factor
notes: Serotonin receptor
- name: SCN5A
association: Risk Factor
notes: Sodium channel
environmental:
- name: Psychological Stress
notes: Major trigger for symptoms
- name: Dietary Triggers
notes: FODMAPs, gluten in some patients
- name: Gastroenteritis
notes: Post-infectious IBS
- name: Antibiotics
notes: May alter microbiome
- name: Early Life Stress
notes: May predispose to IBS
treatments:
- name: Dietary Modification
description: Low FODMAP diet effective in many patients.
- name: Antispasmodics
description: Dicyclomine, hyoscyamine for pain and cramping.
- name: Loperamide
description: For diarrhea-predominant IBS.
- name: Linaclotide
description: Guanylate cyclase agonist for IBS-C.
- name: Rifaximin
description: Non-absorbable antibiotic for IBS-D with bloating.
- name: Tricyclic Antidepressants
description: Low-dose for pain modulation.
- name: SSRIs
description: For patients with comorbid anxiety/depression.
- name: Probiotics
description: May help some patients.
- name: Cognitive Behavioral Therapy
description: Effective for gut-brain axis modulation.
datasets:
# Jejunal biopsy transcriptome in IBS-D
- accession: geo:GSE36701
title: Gene expression analysis of rectal mucosa in chronic irritable bowel
syndrome (IBS) compared to healthy volunteers (HV)
description: >-
Microarray analysis of jejunal mucosal biopsies from 53 IBS-D
(diarrhea-predominant) patients and 40 healthy volunteers to
identify differentially expressed genes related to intestinal
barrier function and visceral hypersensitivity.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_types:
- preferred_term: jejunal mucosa biopsy
tissue_term:
preferred_term: jejunum
term:
id: UBERON:0002115
label: jejunum
sample_count: 93
conditions:
- IBS-D (diarrhea-predominant)
- healthy controls
platform: Affymetrix Human Genome U133 Plus 2.0 Array
notes: >-
Widely used IBS dataset for biomarker discovery. Key targets
identified include EGFR, VEGFA, BCL2L1, CASP9, MMP9, MAPK14.
# IBS-D pilot microarray study
- accession: geo:GSE14841
title: Expression data from healthy volunteers and IBS patients
description: >-
Microarray profiling of jejunal mucosal biopsies from 5 IBS-D
patients and 4 healthy volunteers as a pilot study to characterize
gene expression patterns in diarrhea-predominant IBS.
organism:
preferred_term: human
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: MICROARRAY
sample_types:
- preferred_term: jejunal mucosa biopsy
tissue_term:
preferred_term: jejunum
term:
id: UBERON:0002115
label: jejunum
sample_count: 9
conditions:
- IBS-D (diarrhea-predominant)
- healthy controls
notes: >-
Smaller pilot dataset often combined with GSE36701 for meta-analysis.
Studies have identified 1257 differentially expressed genes between
IBS-D and controls.
# IBS gut microbiota 16S sequencing
- accession: bioproject:PRJNA566284
title: IBS gut microbiota and metabolome profiling
description: >-
16S rRNA gene sequencing of fecal samples from IBS patients and
healthy controls at Beijing Friendship Hospital to investigate
gut microbiota composition and identify potential biomarkers.
organism:
preferred_term: human gut metagenome
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: WGS
sample_types:
- preferred_term: fecal sample
tissue_term:
preferred_term: feces
term:
id: UBERON:0001988
label: feces
sample_count: 29
conditions:
- IBS patients
- healthy controls
notes: >-
Combined with metabolomics data to investigate mechanisms underlying
IBS through microbiologic and metabolomic profiling.
# American Gut Project IBS subset
- accession: mgnify:MGYS00000596
title: American Gut Project
description: >-
16S rRNA V4 region sequencing from the American Gut Project citizen
science initiative. Contains 942 IBS subjects (IBS-D, IBS-C, IBS-U
subtypes) matched with 942 non-IBS controls by age, gender, BMI,
geography, and dietary patterns.
organism:
preferred_term: human gut metagenome
term:
id: NCBITaxon:9606
label: Homo sapiens
data_type: WGS
sample_types:
- preferred_term: fecal sample
tissue_term:
preferred_term: feces
term:
id: UBERON:0001988
label: feces
sample_count: 1884
conditions:
- IBS-D (diarrhea-predominant)
- IBS-C (constipation-predominant)
- IBS-U (unclassified)
- healthy controls
publication: PMID:36573834
notes: >-
Large-scale microbiome study showing IBS-D and IBS-U have reduced
bacterial diversity (Shannon index). Identifies associations between
gut microbiota and depression in IBS subtypes. Bifidobacterium and
SCFA pathways reduced in IBS with depression
references:
- reference: DOI:10.1080/17425255.2024.2349716
title: 'Pharmacogenetics in IBS: update and impact of GWAS studies in drug targets
and metabolism'
findings: []
- reference: DOI:10.1136/gutjnl-2022-328515
title: 'Irritable bowel syndrome: treatment based on pathophysiology and biomarkers'
findings: []
- reference: DOI:10.3390/jcm12072558
title: 'Irritable Bowel Syndrome and the Gut Microbiome: A Comprehensive Review'
findings: []
- reference: DOI:10.3390/medicina61010109
title: 'Impact of Microbiota on Irritable Bowel Syndrome Pathogenesis and Management:
A Narrative Review'
findings: []
- reference: DOI:10.3390/nu17010155
title: 'Exploring Gut Microbiota Imbalance in Irritable Bowel Syndrome: Potential
Therapeutic Effects of Probiotics and Their Metabolites'
findings: []