Microscopic Colitis: The Hidden Cause of Chronic Watery Diarrhea in Older Women and Why It Is Often Missed on Colonoscopy

Research-informed explainer — last updated April 12, 2026

Microscopic colitis causes profuse, chronic watery diarrhea — sometimes 10 or more bowel movements per day — yet the colon looks completely normal to the naked eye during colonoscopy, which is why it is so frequently missed until a gastroenterologist takes targeted biopsies. Once diagnosed, the condition responds well to medication, but the average patient waits years between symptom onset and correct diagnosis.

This article draws on research from five gastroenterologists. Eugene Yen, MD, Associate Professor at Northwestern University Feinberg School of Medicine, published foundational studies on cigarette smoking as a risk factor for microscopic colitis (121 citations), the association between microscopic colitis and reduced colorectal cancer risk (57 citations), and comprehensive reviews of the microscopic colitides (57 citations), as well as reviews on pathogenesis and management (41 citations). Kristin Burke, MD, Assistant Professor at Harvard Medical School and Associate Physician at Massachusetts General Hospital, authored the 2021 Nature Reviews Disease Primers overview of microscopic colitis (79 citations), a nationwide cohort study on inflammatory bowel disease risk in MC patients (57 citations), research on intestinal dysbiosis in MC (52 citations), and a Swedish mortality study (23 citations). Michael Camilleri, MD, at Mayo Clinic, contributed seminal work on intestinal barrier function and its role in diarrheal conditions (858 citations). Prashant Kedia, MD, Medical Director of Interventional Endoscopy at Methodist Dallas Medical Center, published research connecting medication use to microscopic colitis risk (50 citations). William Sandborn, MD, Chief of Gastroenterology at UC San Diego Health, brings expertise in inflammatory bowel disease management and budesonide therapy.

What is microscopic colitis and who gets it

Microscopic colitis (MC) is an inflammatory condition of the colon divided into two histological subtypes: collagenous colitis (CC), defined by a thickened subepithelial collagen band greater than 10 micrometers, and lymphocytic colitis (LC), defined by an increased number of intraepithelial lymphocytes (typically more than 20 per 100 epithelial cells). In both subtypes, the mucosa appears grossly normal on colonoscopy — the inflammation is only visible under the microscope, which is how the condition earned its name.

The condition predominantly affects women over 50, though it occurs in men and younger patients as well. Incidence approaches that of inflammatory bowel disease in some populations. Yen's review of the microscopic colitides highlighted that the condition is far more common than previously recognized, with rising incidence rates possibly related to increased use of triggering medications.

Why the colon looks normal on colonoscopy

The colonoscopic appearance in microscopic colitis is indistinguishable from a normal colon. No ulcers, no erythema, no visible inflammation. This is why patients who undergo colonoscopy for chronic diarrhea and receive a "normal" result may go undiagnosed for years: if the endoscopist does not take biopsies — particularly from multiple segments of the colon including the right side — the diagnosis will be missed entirely.

Burke's 2021 Nature Reviews Disease Primers overview emphasizes that systematic biopsy protocols, sampling from the right colon, transverse colon, and sigmoid colon, are essential for accurate diagnosis. Collagenous colitis in particular can show patchy distribution, meaning a single biopsy from the left colon may be falsely negative.

Medications that trigger microscopic colitis

One of the most clinically important aspects of microscopic colitis is its strong association with specific medications. Kedia's research on medication use and MC identified several drug classes with established links:

• NSAIDs (ibuprofen, naproxen, aspirin): Among the strongest pharmacologic triggers, with evidence of dose-dependent risk
• Proton pump inhibitors (omeprazole, lansoprazole, pantoprazole): Associated with both collagenous and lymphocytic colitis; improvement after PPI withdrawal is well documented
• Selective serotonin reuptake inhibitors (sertraline, paroxetine): Associated particularly with lymphocytic colitis
• Statins and H2-receptor antagonists: Implicated in case series and pharmacovigilance data

For patients who develop MC while taking one of these medications, discontinuation of the suspected agent is the first step, and in some cases is sufficient for remission without additional treatment.

Smoking and other risk factors

Yen's study in Inflammatory Bowel Diseases demonstrated that both current and past cigarette smoking significantly increase the risk for microscopic colitis, with no meaningful difference between the two subtypes. This is notable because smoking is classically thought to be protective against ulcerative colitis — microscopic colitis behaves oppositely. Additional risk factors include celiac disease (which coexists in approximately 5% of MC patients), autoimmune thyroid disease, rheumatoid arthritis, and a personal or family history of other autoimmune conditions.

Camilleri's work on intestinal barrier function provides a mechanistic framework: in MC, disruption of tight junction integrity and altered intestinal permeability allows luminal contents to trigger an inflammatory response in the lamina propria, producing the secretory diarrhea that is the condition's hallmark.

What the research says about treatment

Budesonide is the most robustly evidence-supported treatment for microscopic colitis. Multiple randomized controlled trials have demonstrated clinical remission rates of 80–90% at 6–8 weeks with oral budesonide 9 mg daily. Because budesonide undergoes extensive first-pass metabolism in the liver, systemic side effects are significantly lower than with prednisone, making it the preferred agent over systemic corticosteroids.

For patients who relapse after stopping budesonide — which occurs in 60–80% of patients — maintenance therapy at lower doses (3–6 mg daily) has been shown to sustain remission. Sandborn's extensive IBD experience and work with budesonide formulations informs understanding of how to tailor maintenance regimens.

Burke's nationwide cohort study found that patients with microscopic colitis have a meaningfully elevated risk of subsequently developing Crohn's disease or ulcerative colitis compared to controls, suggesting that MC in some patients may represent early or variant IBD. The Swedish mortality study by Burke's group found that MC patients did not have significantly elevated overall mortality compared to matched controls — reassuring data, but dependent on proper diagnosis and management.

MC is also characterized by intestinal dysbiosis, with the microbiome in MC patients differing significantly from healthy controls, as Burke's 2019 study in Clinical Gastroenterology and Hepatology showed. Whether correcting this dysbiosis through diet or probiotics can contribute to remission is an active area of research.

Questions to ask your doctor

• I have chronic watery diarrhea and my colonoscopy was normal — were biopsies taken from multiple segments, including the right colon?
• Do any of my current medications — PPIs, NSAIDs, or antidepressants — increase my risk for microscopic colitis?
• If I'm diagnosed with microscopic colitis, should I start with stopping triggering medications before trying budesonide?
• What is the recommended duration of budesonide treatment, and what do we do if I relapse after stopping?
• Should I be evaluated for celiac disease or autoimmune thyroid disease given my MC diagnosis?
• How often should I have follow-up to monitor for inflammatory bowel disease?

The bottom line

Microscopic colitis is a genuinely common and treatable cause of chronic watery diarrhea, but it requires a gastroenterologist who knows to take biopsies even when the colonoscopy looks normal. If you have been told your colonoscopy was normal but your diarrhea persists, ask your doctor whether biopsies were taken and whether microscopic colitis has been ruled out. Most patients achieve remission with budesonide, and identifying and stopping the triggering medication may be curative on its own.