Microscopic colitis is a chronic inflammatory bowel disease with significant ramifications for the quality of life of those it affects. Due to its nonspecific symptoms and, in most cases, the macroscopically normal appearance of the colon, the disease risks being underdiagnosed compared to the more classic subcategories of inflammatory bowel disease (IBD), ulcerative colitis and Crohn's disease. However, epidemiological studies show that the incidence of microscopic colitis has exceeded other types of IBD in some countries, especially among the elderly. Physicians should be familiar with the nuances of microscopic colitis and management strategies to tackle this debilitating, underrecognized condition appropriately. 

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What Is Microscopic Colitis?

Microscopic colitis is a chronic inflammatory disease of the colon that was first described in 1980. It has two clinically distinct forms: lymphocytic colitis and collagenous colitis. Both types are characterized by chronic, watery, and non-bloody diarrhea occurring most commonly in female, middle-aged patients. Histological variations distinguish the two subtypes. Lymphocytic colitis is characterized by lymphocytic (white blood cell) infiltration in colonic tissue. In contrast, the diagnostic feature of collagenous colitis is a colonic subepithelial collagen band greater than ten micrometers in thickness. Collagenous and lymphocytic colitis have estimated incidences of 2.0-10.8 and 2.3-16 per 100,000, respectively. (3, 6)

Symptoms of Microscopic Colitis

The hallmark symptom of microscopic colitis is non-bloody, watery diarrhea lasting longer than four weeks. Most patients experience four to nine watery stools daily, although severe disease can cause 15 or more daily bowel movements. Fecal urgency, incontinence, and abdominal pain will accompany diarrhea. Collagenous colitis is often associated with more severe bowel inflammation, and lymphocytic colitis more commonly develops earlier in life. (3, 7)

Like other forms of IBD, extraintestinal symptoms such as weight loss, joint pain, arthritis, and uveitis (inflammation inside the eye) may occur. (3, 6)

What Causes Microscopic Colitis?

The exact cause of microscopic colitis remains unknown, but researchers believe a combination of factors contributes to its development. Immune dysregulation is central to most theories surrounding the etiology and pathophysiology of the disease. Potential factors identified as contributory triggers to an inflammatory, autoimmune cellular response include genetic predisposition, medications, smoking, and altered intestinal epithelial barrier function. (3)

Nonsteroidal inflammatory drugs (NSAIDs) currently have the strongest link to causing flares in microscopic colitis. However, other drugs, including proton pump inhibitors (PPIs), statins, and selective serotonin reuptake inhibitors (SSRIs), have also been implicated as potential causes of the disease. Concomitant use of PPIs and NSAIDs may increase risk even further. (7)

Functional Medicine Labs That Can Help Diagnose Microscopic Colitis

Endoscopic evaluation of the colon with mucosal biopsies is required for diagnosing microscopic colitis and distinguishing between its two subtypes. However, laboratory analysis is warranted before colonoscopy to rule out other common causes of chronic diarrhea. 

Blood Work

A complete blood count (CBC) should be ordered to screen for infection and rule out anemia, which occurs in half of the patients with microscopic colitis. (7) 

A comprehensive metabolic panel (CMP) should be ordered to monitor electrolytes and albumin, which can become unbalanced with chronic diarrhea. 

Celiac disease should be on the differential diagnosis for patients with chronic diarrhea and other gastrointestinal symptoms. Patients with celiac disease are at a higher risk of developing microscopic colitis (3). Celiac serologies can help to rule out celiac disease.

Half of patients with microscopic colitis have an elevated erythrocyte sedimentation rate (ESR), a non-specific inflammatory marker. (7)

Stool Studies

Stool studies screening for gastrointestinal infections should include Clostridioides difficile toxin, routine stool cultures (Salmonella, Shigella, Campylobacter, and Yersinia), Escherichia coli O157:H7, ova and parasites, and Giardia stool antigen.

Increased levels of inflammatory markers, including calprotectin and eosinophil protein X (EPX), have been detected in stool from patients with intestinal pathologies, including microscopic colitis, other types of IBD, celiac disease, and colorectal cancer.

Functional Medicine Labs That Can Help Individualize Treatment for Microscopic Colitis

Functional medicine labs offer a range of diagnostic tests that provide valuable insight into the underlying cause of disease to help healthcare providers individualize treatment for microscopic colitis. 

Comprehensive Stool Analysis

A comprehensive stool analysis measures valuable biomarkers regarding the gut microbiome and digestive health. This stool assessment can identify imbalances in commensal bacteria, pathogens, inflammation markers, and digestive secretions that influence the health and function of the gastrointestinal tract, immune dysregulation, and diarrhea severity.

Food Sensitivities 

A food sensitivity panel aids in tailoring dietary modifications for patients with microscopic colitis. Identifying specific foods that trigger an immune response or exacerbate symptoms can help guide nutritional interventions and reduce symptom severity. By identifying and eliminating trigger foods, patients can experience reduced inflammation, improved gut health, and better management of their microscopic colitis symptoms. 

Autoimmune Panel

Microscopic colitis is believed to have an autoimmune component, and people with concomitant autoimmune disease, including rheumatoid arthritis and type 1 diabetes, are at higher risk for developing microscopic colitis (3). Positive autoantibodies, including antinuclear and antimitochondrial antibodies, antineutrophilic cytoplasmic antibodies, anti-Saccharomyces cerevisiae antibodies, and antithyroid peroxidase antibodies, are found in about half of patients with microscopic colitis (6). An autoimmune panel can identify immune dysregulation and help doctors choose appropriate interventions to target and prevent clinical manifestations of autoimmunity. 

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Conventional Treatment for Microscopic Colitis

All patients with microscopic colitis should be advised to avoid NSAIDs and, if possible, to discontinue all medications associated with the disease. Patients who smoke should be counseled on smoking cessation. (6)  

Per the American Gastroenterological Association (AGA) guidelines, an 8-week course of oral budesonide is the best-documented treatment for achieving remission of microscopic colitis for patients with active disease, defined as at least three stools or at least one water stool daily. Second-line pharmacologic agents include prednisone, bismuth subsalicylate, mesalamine, and cholestyramine (1). Up to 80% of patients will experience clinical relapse after cessation of initial budesonide treatment (6).

Pharmaceutical antidiarrheals, such as loperamide, can be used as needed for the symptomatic management of diarrhea, to be used alone in patients with mild diarrhea, or in conjunction with other therapies (1).

Surgical intervention is rarely required and reserved for those who are unresponsive to all other medical therapies (1).

Functional Medicine Treatment Protocol for Microscopic Colitis

A functional medicine treatment protocol focuses on addressing the root causes of disease, supporting gut health, reducing inflammation, and promoting overall well-being. In alignment with conventional guidelines, the goal of management is to achieve remission of disease and improve the quality of life for the patient.

Therapeutic Diet and Nutrition Considerations for Microscopic Colitis

Diet can play both a causal and therapeutic role in inflammatory bowel diseases. Therefore, a reasonable approach to therapeutic dietary intervention to achieve and maintain disease remission is to propose a well-balanced, anti-inflammatory, and whole-foods diet, such as the Mediterranean diet, excluding identified food triggers. (18)

Elimination Diets

The autoimmune protocol (AIP) diet aims to remove known inflammatory foods, including grains, legumes, dairy, eggs, nuts, nightshades (except sweet potatoes), alcohol, sweeteners, refined sugars, refined oils, food additives, and processed foods. The protocol promotes eating quality meat, seafood, vegetables, fruit, high-quality fats, bone broth, and probiotic foods. (11) 

The Paleo diet, on which the AIP diet is based, tries to adapt available modern foods to mimic as much as possible the hunter-gatherer diet. This means eliminating grains, dairy, legumes, refined sugar, and processed foods. The emphasis is on grass-fed animals, wild-caught fish, fruits, vegetables, nuts, and non-grain oils. (11) 

The Specific Carbohydrate Diet (SCD) was designed in the 1920s by Dr. Sidney Haas to manage celiac disease symptoms in children. Since then, its principles have been extended to managing many gastrointestinal disorders. The purpose of the SCD is to remove difficult-to-digest carbohydrates from the diet to reduce intestinal inflammation. Dietary guidelines propose eliminating grains, refined sugars, processed foods, starchy vegetables, and food additives. Instead, the SCD encourages the consumption of easily digestible carbohydrates, including non-starchy vegetables, fruits, nuts, seeds, and certain dairy products, along with protein from meat and eggs.

Each of these dietary plans may include problematic foods for those with microscopic colitis. Therefore, it is important to help the patient recognize individualized food triggers through observation or food sensitivity testing and modify the diet appropriately.

Fasting

Fasting allows the gut the rest by reducing the workload on the digestive system, giving it time to heal and recover. By abstaining from food for 24-72 hours, fasting can be an exceptionally effective method to induce remission of a microscopic colitis flare. (3)

Supplements Protocol for Microscopic Colitis

Depending on the severity of the disease, a supplemental protocol can be used independently or in conjunction with conventional pharmacologic therapy to induce/maintain disease remission and manage symptoms. Supplements should be used to address underlying factors contributing to immune dysregulation and gastrointestinal inflammation. The below sample protocol is purposed to reduce inflammation and restore the integrity of the intestinal barrier. 

Boswellia serrata

Boswellic acid, the active ingredient derived from the gum resin on Boswellia plants, has been used traditionally for its anti-inflammatory, analgesic, and antibacterial properties in treating inflammatory disorders. A small study confirmed that Boswellia serrata extract increased the clinical remission rate in patients with collagenous colitis.

Dose: 400 mg (80% boswellic acid) three times daily 

Duration: 6 weeks

Curcumin

Curcumin is the potent anti-inflammatory constituent of turmeric (Curcuma longa) that has been extensively studied as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. Many clinical trials have concluded that curcumin effectively reduces IBD symptoms. Several studies have demonstrated its safety in large doses, up to 8,000 mg daily, for up to three months.

Dose: 1 gram twice daily 

Duration: six months

VSL#3

A 2018 systematic review and meta-analysis concluded that probiotics assist in inducing remission of IBD, given their ability to correct dysbiosis and altered bacterial metabolic pathways. VSL#3 is a high-potency probiotic that has been proven effective in treating IBD, including microscopic colitis.

Dose: 900 billion CFU daily

Duration:  8 weeks

Serum-Derived Bovine Immunoglobulin (SBI)

Immunoglobulins, or antibodies, modulate the immune response in the gut, reduce inflammation, and combat pathogens in the gastrointestinal tract. Research suggests that therapy with 5-10 grams of SBI daily provides benefits in managing gastrointestinal symptoms and should be considered as nutritional support for patients with IBD who are not fully managed on traditional therapies. (17, 22)

Dose: 2.5 grams twice daily (up to 10 grams daily)

Duration:  4-6 weeks

When to Retest Labs

Improvement in clinical outcomes can be noted in as soon as four weeks with an effective treatment protocol. Monitoring patient response to treatment is usually performed by tracking inflammatory markers and symptom improvement at this time. Additional labs may be ordered as needed to monitor for signs of dehydration and infection. Functional medicine labs, generally less likely to be covered by insurance, are often reordered between 6-12 months after treatment initiation for financial reasons, but may be repeated sooner based on clinical necessity.  

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Summary

A functional medicine protocol for treating microscopic colitis takes a comprehensive and personalized approach to address the underlying causes, support gut health, and reduce inflammation. By implementing a customized diet that eliminates trigger foods, supporting the gut microbiome, and incorporating appropriate supplements, individuals with microscopic colitis can experience improved symptom management and a better quality of life.