Overview

Pouchitis refers to inflammation of the surgically created ileal pouch, usually performed for severe ulcerative colitis or sometimes Crohn’s colitis through ileal pouch-anal anastomosis (IPAA). During this procedure, the colon and rectum are removed, and a J-shaped pouch is formed from the small intestine, which is then connected directly to the anus.¹

Common clinical symptoms and diagnostic challenges

Patients who develop pouchitis often experience a variety of gastrointestinal symptoms. These commonly include: increased stool frequency, urgency, abdominal cramping, bloating, and a sensation of pelvic pressure or heaviness. In some cases, patients may also report nocturnal incontinence, characterised by the involuntary passage of stool during the night.²

These symptoms often overlap with other gastrointestinal conditions, making diagnosis challenging.

Need for noninvasive biomarkers in diagnosis and monitoring

The increased prevalence of inflammatory bowel disease (IBD), combined with the increasing number of newly diagnosed cases, calls for improved, noninvasive diagnostic and monitoring tools. While current laboratory tests, such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and complete blood count, are routinely used, they lack specificity for intestinal inflammation and are insufficient for accurate diagnosis of intestinal inflammation. 

Endoscopy remains the gold standard for diagnosing IBD. However, the invasive nature, requirement for sedation or general anaesthesia (especially in children), and the potential risks and discomfort from the procedure make it less ideal for routine screening or disease monitoring.³

Additionally, the clinical symptoms of IBD often overlap with other gastrointestinal conditions, such as bowel disorders or infections, making diagnosis particularly difficult. Studies have shown that in a significant proportion of suspected IBD cases, endoscopy does not confirm the initial clinical diagnosis, leading to unnecessary procedures. This has driven the search for reliable, noninvasive biomarkers, such as faecal calprotectin (FC), for reducing unnecessary procedures.³

Understanding FC

What is FC?

FC is a protein released by activated neutrophils (immune cells) in the intestinal mucosa during inflammation. The presence of calprotectin in faeces results from the migration of neutrophils into the gastrointestinal mucosa in response to intestinal inflammation. During this inflammatory process, neutrophils infiltrate the intestinal lining and release calprotectin, which is then excreted in the stool.⁴ 

Both in vitro and in vivo results show that FC is highly stable and resistant to degradation by intestinal enzymes as well as by bacterial activity. Its biochemical stability, even distribution in stool and preservation at room temperature for up to one week make FC a practical and reliable biomarker for clinical use. These properties facilitate sample collection and transport without compromising test accuracy. Moreover, since stool comes into direct contact with the intestinal mucosa, faecal biomarkers like calprotectin offer a more accurate reflection of local gastrointestinal inflammation than serum-based markers.⁴

Pouchitis and the role of faecal calprotectin

Pathophysiology of pouchitis

Pouchitis develops due to multiple factors: altered gut microbiota, immune dysregulation, antibiotic overuse, and colonic metaplasia, which leads to histological changes like inflammation, crypt distortion, and villous atrophy. These complex, multifactorial processes contribute to pouch inflammation and symptoms.^5,6

Rationale for using faecal calprotectin as a biomarker in pouchitis

FC provides a noninvasive and cost-effective method to screen for inflammation, predict relapse, monitor treatment response, and identify patients who need further investigation. Its use reduces reliance on invasive endoscopic procedures and offers real-time insights into disease activity.

Diagnostic utility of faecal calprotectin in pouchitis

Evidence supporting elevated levels during active pouchitis

A systematic review by McKechnie et al. evaluated seven studies with 256 patients, confirming FC as a reliable diagnostic tool for acute pouchitis.⁷ Pous-Serrano et al. also reported that higher pre-surgical FC levels in Crohn’s disease patients correlated with more severe bowel inflammation.⁸ Ollech et al. also found that FC levels rose with higher endoscopic and histologic scores and outperformed CRP in predicting pouchitis.⁹

Comparison of FC and endoscopy

Faecal calprotectin (FC) and endoscopy are two key methods used to assess inflammation in patients with pouchitis. FC is a non-invasive stool-based biomarker that reflects intestinal inflammation and is particularly useful for screening and monitoring disease activity. Endoscopy, in contrast, is an invasive visual examination that allows direct assessment of the pouch mucosa and enables biopsies to detect histologic changes or complications.^7,9

Table 1. Comparative overview of faecal calprotectin and endoscopy in pouchitis evaluation

Cut-off values and sensitivity/specificity

FC cut-off values for pouchitis range from 56–494 μg/g, with sensitivity up to 92%, making it effective for ruling out active inflammation.⁷

Monitoring disease activity and response to therapy

FC is particularly valuable for evaluating responses to medications such as:

• Aminosalicylates (e.g., 5-ASA)4
• Corticosteroids
• Immune-modifying agents
• Antibiotics
• Biologics (e.g., anti-TNF drugs)

Low FC levels indicate effective therapy, while rising levels may signal relapse, guiding dose adjustments and reducing unnecessary endoscopy. FC also helps predict corticosteroid response in acute severe colitis and may reduce overtreatment.⁴

Clinical application and limitations

Faecal calprotectin offers several advantages in the diagnosis and monitoring of IBD, particularly pouchitis. It is noninvasive, cost-effective, and correlates well with endoscopic and histologic findings, making it a valuable tool for assessing mucosal inflammation and treatment response. However, its use also comes with challenges. There is notable inter- and intra-individual variability in FC levels, and results can be influenced by co-existing conditions such as gastrointestinal infections. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to elevate FC independently of IBD activity. Additionally, differences in assay methods and cutoff values between testing kits limit standardisation. 

FC should be interpreted cautiously and used in combination with clinical symptoms, endoscopic evaluation, and histologic evidence to guide accurate diagnosis and effective management.⁴

Future directions and research needs

There is an urgent need for standardised cut-off values, as current variability among assay methods limits their use in the clinic and comparison with other patients’ data. Establishing consistent thresholds would help in accurate diagnosis and treatment monitoring. Additionally, faecal calprotectin may be useful in guiding personalised treatment strategies, such as changing medication intensity or assessing relapse risk. Combining FC with other biomarkers like lactoferrin, serum inflammatory markers, or microbiome profiles may also further enhance diagnostic accuracy and enable personalised treatment strategies.⁷

Summary

• FC is a stable, noninvasive stool biomarker reflecting ileal pouch inflammation
• It correlates strongly with endoscopic (PDAI) and histologic disease activity
• Rising FC levels predict relapses, guide therapy adjustments, and reduce unnecessary endoscopies
• Limitations include assay variability and influence from other conditions; standardisation is needed