Offer for Students ₹ 999 INR ( offer valid till 31st December 2025)
Differential diagnosis of intestinal dyspepsia: distinguishing IBS, Crohn’s disease, ulcerative colitis, and biliary dyskinesia
Authors:
1. Musaeva Begaiym
2. Abhay Raj Chauhan
3. Robin Sharma
4. Tauheed Alam
5. Anurag Patel
6. Taj Babu
7. Saquib Mohammad
8. Sonu Verma
(1, Teacher , International Medical Faculty , Osh State University , Kyrgyzstan
2,3,4,5,6,7,8, Student , International Medical Faculty , Osh State University , Kyrgyzstan)
Abstract
Patients with chronic upper or lower abdominal discomfort often present with “intestinal dyspepsia,” a symptom complex that can reflect functional disorders (e.g., irritable bowel syndrome IBS), organic inflammatory disease (Crohn’s disease, ulcerative colitis collectively IBD), or biliary dyskinesia. Early, accurate differentiation reduces unnecessary invasive testing and speeds targeted therapy. To synthesize recent evidence on clinical features, biomarkers, imaging, and recommended diagnostic algorithms that differentiate IBS from IBD (Crohn’s and UC) and from biliary dyskinesia. Structured literature search (PubMed, PMC, Google Scholar) for guidelines, systematic reviews, meta-analyses, and high-quality original studies through 2025. Key diagnostic performance data for fecal calprotectin, imaging, and HIDA scan ejection fraction (EF) are summarized. Fecal calprotectin is a robust noninvasive discriminator between IBD and functional disorders (high sensitivity and specificity at typical cutoffs). Rome IV criteria remain central to IBS diagnosis but do not exclude organic disease. Alarm features (weight loss, bleeding, anemia, persistent vomiting) greatly increase prior probability of organic disease and warrant endoscopy/imaging. HIDA with CCK and gallbladder EF thresholds (commonly <35–40% for hypokinetic and ≥80% for hyperkinetic patterns) help identify biliary dyskinesia, though indications for cholecystectomy require careful selection. Emerging tools (CT/MRI patterns, serologic markers, and machine-learning classifiers) show promise in subtype differentiation and risk stratification. A stepwise algorithm combining careful history/exam, alarm-feature screening, fecal calprotectin, targeted endoscopy/imaging, and selective hepatobiliary scintigraphy optimizes distinction among IBS, IBD, and biliary dyskinesia. Research priorities include standardizing HIDA definitions and integrating multi-omic/ML models into clinical workflows.
Introduction
“Intestinal dyspepsia” is a pragmatic clinical label often applied when patients present with chronic abdominal discomfort, bloating, early satiety, altered bowel habits, or pain. Differentiating functional disorders such as irritable bowel syndrome (IBS) from organic inflammatory bowel disease (IBD — Crohn’s disease [CD] and ulcerative colitis [UC]) and biliary motility disorders (biliary dyskinesia) is a common diagnostic challenge (Francis, 2024; Schmulson & Drossman, 2017). Accurate differentiation matters because therapies diverge (antispasmodics/neuromodulators for IBS; immunomodulators and biologics for IBD; cholecystectomy or endoscopic interventions for biliary dyskinesia) and because misclassification delays effective care (Moayyedi et al., 2017).
Historically, symptom-based criteria (Rome IV) were developed to identify IBS but have limitations: symptoms overlap with organic disease, and alarm features must be sought to avoid missed diagnoses (Schmulson & Drossman, 2017; Goodoory et al., 2024). Noninvasive biomarkers—most notably fecal calprotectin (FC)—have emerged as practical triage tools to separate inflammatory from functional etiologies (Walsham & Sherwood, 2016; Dajti et al., 2023). Meanwhile, biliary dyskinesia remains controversial with variable diagnostic thresholds for gallbladder ejection fraction (GBEF) and mixed evidence on outcomes after cholecystectomy (Popov et al., 2025; Camacho et al., 2024). This review synthesizes current evidence and proposes a practical diagnostic pathway.
Methods
Literature search strategy
We performed a structured literature search (PubMed/PMC, Google Scholar, AAFP/ACG websites, and key journal platforms) to identify guidelines, systematic reviews, meta-analyses, and original diagnostic studies relevant to differentiating IBS, Crohn’s disease, ulcerative colitis, and biliary dyskinesia. Search terms included combinations of: “IBS Rome IV,” “fecal calprotectin meta-analysis,” “Crohn’s vs ulcerative colitis differentiation,” “alarm features dyspepsia endoscopy guidelines,” “biliary dyskinesia HIDA ejection fraction,” and “diagnostic algorithm IBS vs IBD.” Searches included articles through 2025. Relevant guideline documents (ACG, NICE), narrative reviews, and high-impact primary studies were prioritized. (Examples: Rome IV overview, ACG dyspepsia guideline, multiple meta-analyses of fecal calprotectin, recent reviews on HIDA and biliary dyskinesia.) (Rome Foundation)
Inclusion/exclusion criteria
Included: meta-analyses, systematic reviews, clinical guidelines, large cohort studies, diagnostic accuracy studies, and recent narrative reviews addressing clinical features, noninvasive biomarkers (esp. fecal calprotectin), endoscopy/imaging, and hepatobiliary scintigraphy. Excluded: small case reports without diagnostic data, outdated diagnostic thresholds superseded by guidelines, and non-English papers lacking translation.
Data extraction and synthesis
For diagnostic accuracy data (fecal calprotectin, HIDA EF), we extracted sensitivity/specificity, cutoff values, and study population characteristics. For clinical guidance, we extracted recommended algorithms for initial triage (history, alarm features, noninvasive testing) and indications for invasive testing (endoscopy, colonoscopy, imaging). Emerging diagnostics (imaging features, ML approaches) were summarized qualitatively. Key findings were synthesized into a stepwise diagnostic approach. (Specific primary sources and meta-analyses are cited in Results and References.) (PMC)
Results
Epidemiology and pretest probability considerations
Functional dyspepsia and IBS are common: most patients with dyspepsia have functional disorders rather than organic pathology (Francis, 2024; Mounsey & AAFP, 2020). Conversely, IBD has lower population prevalence but higher individual morbidity and clear objective markers on endoscopy/biopsy (Ranasinghe, 2024). Biliary dyskinesia is less common and variably reported depending on referral patterns and HIDA criteria used (Simngam et al., 2025; Elaskandrany, 2025). (NCBI)
Clinical features and alarm symptoms
IBS (per Rome IV): Recurrent abdominal pain related to defecation, changes in stool frequency/form; predominately functional with gut–brain interaction mechanisms (Schmulson & Drossman, 2017; Khasawneh et al., 2023). Rome IV remains the standard diagnostic framework but requires clinicians to rule out red flags. (PMC)
IBD (Crohn’s, UC): Systemic features (fever, weight loss), nocturnal symptoms, bleeding, significant inflammatory markers (CRP, ESR), and endoscopic/histologic inflammation. Crohn’s often causes transmural disease, skip lesions, and small bowel involvement; UC typically causes continuous mucosal disease starting from rectum (Ranasinghe, 2024; Yamamoto et al., 2024). (NCBI)
Biliary dyskinesia: Biliary colic-type pain (epigastric/right-upper quadrant postprandial pain), absence of gallstones on ultrasound, and abnormal gallbladder emptying on HIDA with CCK stimulation. Definitions vary (GBEF <35–40% hypokinetic; some define hyperkinetic as ≥80%). Clinical selection is key because not all patients with abnormal EF benefit from cholecystectomy (Popov et al., 2025; Camacho et al., 2024). (PMC)
Diagnostic utility of fecal calprotectin (FC)
Multiple meta-analyses and systematic reviews confirm FC’s excellent sensitivity and specificity for distinguishing IBD from functional disorders (Dajti et al., 2023; Walsham & Sherwood, 2016; de Magalhães Costa et al., 2024). A commonly used cutoff is ~50 µg/g to maximize sensitivity for organic disease; higher cutoffs raise specificity at the cost of sensitivity. FC performs better in Western cohorts and is a cost-effective triage test to reduce unnecessary colonoscopies (Dajti et al., 2023; AAFP review). (PubMed)
Example pooled estimates: meta-analyses report pooled sensitivity often >0.90 and specificity commonly >0.80 at typical cutoffs, though heterogeneity exists across studies (Walsham & Sherwood, 2016; Dajti et al., 2023). (PMC)
Role of basic labs and imaging
Serum CRP and ESR: helpful but less specific than FC for mucosal inflammation (de Magalhães Costa et al., 2024). Abdominal ultrasound and CT/MR enterography are useful when small bowel Crohn’s is suspected or to evaluate biliary causes. CT/MR fat patterning and distribution may assist differentiation of UC vs CD in some cases (Yamamoto et al., 2024). (PMC)
HIDA (hepatic iminodiacetic acid) scan and biliary dyskinesia
HIDA with CCK provocation measuring GBEF is the principal functional test. Typical diagnostic thresholds vary: many centers use <35–40% for reduced EF and consider ≥80% for hyperkinetic patterns (Popov et al., 2025; Camacho et al., 2024). Evidence on post-cholecystectomy outcomes is mixed; appropriate patient selection (classic biliary pain, no stones, abnormal EF, and exclusion of other causes) correlates best with symptom relief (Elaskandrany, 2025; Popov et al., 2025). (PMC)
Diagnostic algorithm (synthesis)
History & exam: apply Rome IV for IBS but actively screen for alarm features (weight loss, bleeding, anemia, nocturnal symptoms, family history). If alarm features present → proceed to endoscopy/colonoscopy and targeted imaging. (PMC)
Noninvasive triage: if no alarm features, obtain fecal calprotectin. FC ≤50 µg/g suggests functional disorder (IBS) — consider symptomatic management and close follow-up. FC >50–100 µg/g suggests need for endoscopic evaluation for IBD. (PubMed)
Imaging & targeted tests: if small-bowel Crohn’s suspected (left/right pain, malabsorption, focal tenderness), obtain cross-sectional imaging (MR enterography/CT). If biliary pain pattern and negative ultrasound for stones, consider HIDA with CCK to measure GBEF and evaluate biliary dyskinesia. (PMC)
Endoscopy & histopathology: colonoscopy with biopsies remains gold standard for IBD diagnosis and subtyping (UC vs CD) (Ranasinghe, 2024). (NCBI)
Emerging tools and research directions
Machine learning models combining symptoms, labs, and imaging show potential in subtype classification and prognostication (Huang et al., 2025). (tgh.amegroups.org)
Multi-omic approaches (microbiome, proteomics) are under active study to refine discrimination between functional and organic disease and to predict treatment response (Wang, 2025). (MDPI)
Discussion
This synthesis supports a pragmatic, evidence-based, stepwise approach to patients presenting with intestinal dyspepsia. The combination of careful clinical assessment (identifying alarm features and symptom patterns), fecal calprotectin as a front-line noninvasive biomarker, selective cross-sectional imaging, and targeted functional hepatobiliary testing (HIDA) yields efficient triage that minimizes unnecessary invasive procedures while identifying patients who require prompt endoscopic/histologic evaluation.
Fecal calprotectin is the most validated noninvasive discriminator between IBD and functional disorders; meta-analyses consistently report high sensitivity and good specificity, making FC suitable as a gatekeeper for colonoscopy (Walsham & Sherwood, 2016; Dajti et al., 2023). However, clinicians should be aware of false positives (e.g., infectious colitis, NSAID use) and false negatives at low disease burden (de Magalhães Costa et al., 2024). (PMC)
Rome IV criteria remain useful but are insufficient alone; their performance improves when combined with objective testing and when alarm features prompt immediate investigation (Schmulson & Drossman, 2017; Goodoory et al., 2024). (PMC)
Biliary dyskinesia is diagnostically challenging. Although many centers use GBEF thresholds to define dysfunction, the literature reveals heterogeneity in cutoff values and outcome studies; therefore, patient selection (classic biliary pain, exclusion of other causes, abnormal EF) is crucial for predicting benefit from cholecystectomy (Popov et al., 2025; Elaskandrany, 2025). Prospective trials and standardized HIDA protocols are needed. (PMC)
Limitations: This review is narrative and not a formal systematic review with a PRISMA flowchart. Although the literature search prioritized high-quality sources to 2025, heterogeneity between studies (different FC cutoffs, variable HIDA protocols) complicates pooled diagnostic thresholds. Future research should standardize test protocols and evaluate combined diagnostic algorithms prospectively. (PubMed)
Conclusion
For patients with intestinal dyspepsia without alarm features, a pragmatic pathway using Rome IV symptom assessment plus fecal calprotectin provides an efficient, evidence-based approach to distinguish IBS from IBD. When biliary pain patterns suggest gallbladder dysfunction and ultrasound is negative for stones, HIDA with CCK (with careful consideration of GBEF thresholds) can identify biliary dyskinesia in appropriately selected patients. Future efforts should focus on standardized HIDA definitions, prospective validation of integrated algorithms, and the incorporation of multi-omic/ML tools to improve diagnostic precision.
Practical diagnostic algorithm.
Take focused history (pain pattern, stool changes), apply Rome IV, and screen for alarm features. (PMC)
If no alarm features → order fecal calprotectin. (PMC)
FC ≤50 µg/g → manage as IBS (treat symptomatically; follow up). FC >50–100 µg/g → colonoscopy ± imaging for IBD. (PubMed)
Suspected biliary pain with negative ultrasound → HIDA with CCK to measure GBEF and consider surgical referral if criteria and clinical picture align. (PMC)
References
AAFP. (2021). Fecal Calprotectin for the Evaluation of Inflammatory Bowel Disease. American Family Physician. Retrieved from https://www.aafp.org/pubs/afp/issues/2021/0900/p303.html. (AAFP)
Camacho, K. D., et al. (2024). Hyperkinetic biliary dyskinesia: An underrecognized clinical entity. Journal/PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11281832/. (PMC)
Carmona-Sánchez, R. I., et al. (2025). Good clinical practice recommendations for the diagnosis of dyspepsia. Journal. Retrieved from https://www.sciencedirect.com/science/article/pii/S2255534X25000386. (ScienceDirect)
Dajti, E., et al. (2023). Diagnostic performance of fecal calprotectin in distinguishing IBD from IBS: Systematic review and meta-analysis. Alimentary Pharmacology & Therapeutics. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37823411/. (PubMed)
de Magalhães Costa, M. H., et al. (2024). Fecal calprotectin and endoscopic scores in IBD: A meta-analysis. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11230062/. (PMC)
Elaskandrany, M. A. (2025). Biliary dyskinesia with reduced gallbladder ejection fraction — diagnostic and therapeutic considerations. Retrieved from https://bhm.scholasticahq.com/article/127836-biliary-dyskinesia-with-reduced-gallbladder-ejection-fraction-a-diagnostic-and-therapeutic-shift-in-management. (bhm.scholasticahq.com)
Francis, P. (2024). Functional dyspepsia: StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK554563/. (NCBI)
Goodoory, V. C., et al. (2024). Validating modifications to Rome IV criteria in IBS. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11671724/. (PMC)
Huang, J., et al. (2025). Machine learning in the differential diagnosis of ulcerative colitis and Crohn’s disease: systematic review. Retrieved from https://tgh.amegroups.org/article/view/9632/html. (tgh.amegroups.org)
Khasawneh, M., et al. (2023). A diagnosis of irritable bowel syndrome using Rome IV: cohort study. ScienceDirect. Retrieved from https://www.sciencedirect.com/science/article/pii/S1542356523004445. (ScienceDirect)
Lichtenstein, G., et al. (ACG). (Guidelines). ACG clinical guidance and resources. American College of Gastroenterology. Retrieved from https://gi.org/guidelines/. (American College of Gastroenterology)
Mounsey, A., & AAFP. (2020). Functional dyspepsia: Evaluation and management. American Family Physician. Retrieved from https://www.aafp.org/pubs/afp/issues/2020/0115/p84.html. (AAFP)
Moayyedi, P., et al. (2017). ACG and CAG Clinical Guideline: Management of Dyspepsia. Retrieved from https://pubmed.ncbi.nlm.nih.gov/28631728/. (PubMed)
Popov, J. L., et al. (2025). Biliary dyskinesia — contemporary review and outcomes after cholecystectomy. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11967721/. (PMC)
Ranasinghe, I. R. (2024). Crohn Disease. StatPearls. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK436021/. (NCBI)
Sarnelli, G., et al. (2025). Italian guidelines for the diagnosis and treatment of functional GI disorders. DLD Journal. Retrieved from https://www.dldjournalonline.com/article/S1590-8658%2825%2900830-8/pdf. (dldjournalonline.com)
Schmulson, M., & Drossman, D. A. (2017). What is new in Rome IV. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC5383110/. (PMC)
Simngam, N., et al. (2025). Prevalence and factors associated with organic dyspepsia. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC12043867/. (PMC)
Van Rheenen, P. F., et al. (Meta-analysis cited within Walsham). (Earlier meta-analyses on FC). See Walsham & Sherwood (2016). (PMC)
Walsham, N. E., & Sherwood, R. A. (2016). Fecal calprotectin in inflammatory bowel disease: a review. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC4734737/. (PMC)
Wang, W., et al. (2025). The role of calprotectin and proteomics in IBD diagnosis. MDPI. Retrieved from https://www.mdpi.com/1422-0067/26/5/1996. (MDPI)
de Magalhães Costa, M. H., et al. (2024). Fecal calprotectin and endoscopic scores in IBD. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11230062/. (PMC)
Dajti, E., et al. (2023). Faecal calprotectin diagnostic meta-analysis. PubMed. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37823411/. (PubMed)
El-Badry, A. (2010). Faecal calprotectin differentiating functional vs organic bowel disease. ScienceDirect. Retrieved from https://www.sciencedirect.com/science/article/abs/pii/S1687197910000523. (ScienceDirect)
Yamamoto, S., et al. (2024). Differentiation between UC and Crohn’s using imaging and fat patterning. PMC. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC11151137/. (PMC)
Huang, J., et al. (2025). Machine learning for IBD subtyping. AME Publishing. Retrieved from https://tgh.amegroups.org/article/view/9632/html. (tgh.amegroups.org)
