Microscopic colitis is the often lesser recognized form of inflammatory bowel disease, alongside Crohn's disease and ulcerative colitis. The incidence of microscopic colitis has increased over time, affecting the older population predominantly. Chronic inflammation of the colonic tissues causes significant watery diarrhea and impaired quality of life.

Conventional pharmacologic management techniques can effectively induce remission of the disease but don't address the underlying causes of inflammation, so a return of symptoms once therapy is terminated is common.

A functional approach to microscopic colitis includes specialty testing to identify known contributing factors leading to chronic gastrointestinal inflammation. Alternative treatment approaches can successfully remove immunological triggers to restore balance to the immune system, reduce inflammation, and resolve colonic inflammation.

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What is Microscopic Colitis?

Microscopic colitis is a chronic inflammatory disease of the colon that is characterized by watery, non-bloody diarrhea. It becomes more common as we age and can be easily confused with other gastrointestinal conditions, like irritable bowel syndrome and infection. Microscopic colitis is a subset of inflammatory bowel disease (IBD). Different types of IBD include Crohn's disease and ulcerative colitis. (2)

There are two types of microscopic colitis: lymphocytic colitis and collagenous colitis. The two types of microscopic colitis appear similarly in clinical presentation and macroscopic appearance of the colonic mucosa. Differentiating the two, however, are key microscopic changes to colonic tissue that can be identified with a colonic mucosal biopsy. (1)

Lymphocytic Colitis

When inspected under the microscope, the diagnostic feature of lymphocytic colitis is the increase of white blood cells (lymphocytes) in colonic tissue. Lymphocytic colitis incidence is estimated to be 2.3-16 cases per 100,000 annually. (3, 4)

Collagenous Colitis

The layer of collagen (protein) under the cells lining the colon becomes thicker than usual in collagenous colitis. On biopsy, a subepithelial collagen band greater than 10 micrometers is diagnostic for collagenous colitis. The incidence of collagenous colitis is estimated to be 2.0-10.8 cases per 100,000 annually. (3, 4)

Microscopic Colitis vs. Ulcerative Colitis

Microscopic colitis and ulcerative colitis (UC) are both IBD subtypes that lead to chronic inflammation of the large intestine. UC occurs when the immune system attacks tissue in the large intestine, causing ulcerative lesions contained to the colon. 

Microscopic colitis and UC cause diarrhea, fecal urgency, abdominal pain, and weight loss. The main distinguishing symptom between the two is that UC causes bloody diarrhea, whereas microscopic colitis does not. Additionally, the colonic tissue appears unaffected in patients with microscopic colitis undergoing colonoscopy, whereas macroscopic inflammation is easily visualized in patients with UC. (5)

The exact cause of these diseases is unclear, but genetics and environmental risk factors appear to be involved in both (5).

Unmanaged ulcerative colitis increases the risk for health complications, including colorectal cancer, blood clots, and osteoporosis. This 2019 study found that people with microscopic colitis have a 17 times greater risk of developing ulcerative colitis than the general public. However, most cases of microscopic colitis have good prognoses and are not associated with severe health complications (1).

Microscopic Colitis Symptoms

The predominant symptom of microscopic colitis is chronic, watery, non-bloody diarrhea that comes and goes, lasting up to months at a time. Fecal urgency and incontinence may accompany diarrhea. Additional gastrointestinal symptoms common in patients with microscopic colitis include abdominal pain and cramping, bloating, and nausea. Because of the similarity in symptoms, patients with microscopic colitis are commonly misdiagnosed with irritable bowel syndrome (IBS). (1, 2)

The severity of symptoms can vary between patients. Most people with microscopic colitis have between four and nine bowel movements daily, but over 15 bowel movements have been reported in severe cases. (3)

Patients may also experience extraintestinal symptoms, including joint pain, arthritis, and eye inflammation (uveitis) (3).

Complications of severe, untreated chronic diarrhea include fatigue, weight loss, and dehydration. Unlike other forms of IBD, microscopic colitis does not increase the risk of colon cancer. (2) 

Causes of Microscopic Colitis

The exact cause of microscopic colitis is unclear. However, like other forms of IBD, the cause of microscopic colitis is likely multifactorial, resulting from exaggerated immune responses to gastrointestinal luminal factors in genetically susceptible individuals. (3)

Risk Factors

Older age increases the risk of developing microscopic colitis. Microscopic colitis is most common in people ages 50-70. (1)

Women are more likely to have microscopic colitis than men (1). Studies have suggested that estrogen-containing hormone replacement therapy and oral contraceptives increase the risk of microscopic colitis.

Genetics

Research suggests the role of genetic variation in the human leukocyte antigens (HLA) markers in the development of microscopic colitis, especially the collagenous colitis subtype. 

Abnormal autoimmune reactions likely play a role in the pathogenesis of microscopic colitis, and people with concurrent autoimmune diseases, including celiac disease, rheumatoid arthritis, and type 1 diabetes, are at higher risk for developing microscopic colitis. (2)

Abnormal Collagen Metabolism

The accumulation of collagen in collagenous colitis has been affiliated with abnormal collagen metabolism due to increased expression of transforming growth factor (TGF) beta-1, which influences the balance between connective tissue formation and breakdown. (3, 4)

Altered Epithelial Barrier Function

The altered epithelial barrier function of the intestine, leading to hyperpermeability of the intestines and immune dysregulation and intestinal inflammation, is also a proposed mechanism in the development of microscopic colitis (3). 

Gastrointestinal infections, dysbiosis, and adverse food reactions are common inducers of intestinal permeability, or "leaky gut." Clostridium difficile, Yersinia enterocolitica, and Helicobacter pylori have been suggested as bacterial culprits related to the onset of microscopic colitis (3). Research also confirms the Epstein-Barr virus (EBV) in mucosal colonic cells of patients with microscopic colitis (6, 7).

Bile Acid Malabsorption

Bile acid malabsorption, a common cause of chronic diarrhea and abdominal pain, is commonly found concurrently in patients with microscopic colitis. Bile acids insufficiently absorbed in the small intestine travel to the colon, increasing large intestinal motility and secretions. 

Lifestyle Factors

Smoking significantly increases the risk of both types of microscopic colitis. Smokers are likely to develop microscopic colitis at a younger age; this study concluded that the onset of the disease occurs more than ten years earlier in smokers.

Medication use can also increase the risk of developing microscopic colitis. Medications associated with microscopic colitis include nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), antidepressant SSRIs, beta-blockers, and cholesterol-lowering statins. (2)

Functional Medicine Labs to Test for Root Cause of Microscopic Colitis

Flexible sigmoidoscopy or colonoscopy with biopsy is required to diagnose microscopic colitis and differentiate between lymphocytic colitis and collagenous colitis. Specialty labs can identify imbalances and triggers of the disease process to help guide effective root-cause treatment strategies.

Comprehensive Stool Test

Comprehensive stool tests provide an in-depth evaluation of commensal, opportunistic, and pathogenic intestinal microorganisms; digestion and absorption markers; short-chain fatty acids (SCFAs); and immune and inflammatory markers specific to the gut.

The GI-MAP + Zonulin test by Diagnostic Solutions and the GI Effects® Comprehensive Profile from Genova Diagnostics are commonly ordered comprehensive stool analysis' that can identify dysbiosis, intestinal infection, bile acid malabsorption, and intestinal hyperpermeability contributing to the development and severity of microscopic colitis.

Food Testing

Blood panels to detect food allergies and food sensitivities contributing to leaky gut and exaggerated immune responses are routinely ordered during the diagnostic evaluation of most gastrointestinal conditions. 

Given the known association between the two conditions, all patients with microscopic colitis should be screened for Celiac disease and gluten sensitivity.

Autoimmune Panel

An autoimmune panel measures antinuclear antibodies (ANA) and other autoimmune markers to help diagnose autoimmune disease cooccurring with microscopic colitis. 

Hemoglobin A1c (HbA1c) is the 3-month blood sugar average used to diagnose and monitor patients with type 1 diabetes.

EBV Panel

Acute and chronic EBV infections can be diagnosed with a comprehensive blood panel that measures antibodies against multiple proteins of the EBV structure.

Assessment for Dehydration

Your doctor may recommend a comprehensive metabolic panel (CMP) and a urinalysis to screen for dehydration, assessed by imbalances in sugar and electrolytes secondary to chronic diarrhea.

Conventional Treatment for Microscopic Colitis

Per the American Gastroenterological Association (AGA), the minimally-absorbed oral steroid budesonide is the best-documented treatment for microscopic colitis. Cessation of therapy can be considered after an 8-week course; however, relapse occurs in two-thirds of patients once treatment is withdrawn. Second-line pharmacologic agents to budesonide include prednisone, bismuth subsalicylate, and mesalamine.

Functional Medicine Treatment for Microscopic Colitis

Functional medicine can help address the root causes of microscopic colitis. Below are some of the most common treatments used by functional medicine practitioners.

Diet for Microscopic Colitis

An elimination-rechallenge diet is routinely implemented for patients with microscopic colitis to identify food reactions. Results from food sensitivity testing can determine which foods to eliminate from the diet. A 6-8 week elimination diet is then followed by a rechallenging of each food to observe for negative gastrointestinal symptoms that would indicate a trigger to the disease. Patients can reincorporate well-tolerated foods into the diet but should continue avoiding the foods that trigger symptoms.

Fasting has also been reported to stop diarrhea due to microscopic colitis, likely due to its ability to reduce oxidative stress and lower systemic, chronic inflammation (8, 9). An elemental diet (ED), a predigested, hypoallergenic formula designed to provide digestive relief and commonly implemented in managing gastrointestinal diseases, can also be recommended to patients with microscopic colitis. Although little research has been conducted in patients with microscopic colitis, the research strongly supports the beneficial effects of the ED in patients with other forms of IBD, like Crohn's disease.

Herbs for Inflammation

Boswellia serrata (frankincense) is an anti-inflammatory and analgesic herb commonly implemented in functional medicine protocols to address arthritis, UC, and other inflammatory conditions. Although more extensive trials are needed to confirm results, promising, smaller trials have concluded that Boswellia serrata extract is more effective than a placebo at inducing remission of collagenous colitis.

Curcumin, the medicinal compound extracted from turmeric (Curcuma longa), is widely used for its antioxidant and anti-inflammatory effects. Used in its whole-food or supplemental form, curcumin has been shown to reduce gastrointestinal inflammation.  

Ginger root (Zingiber officinale) is another food-as-medicine botanical routinely implemented in functional medicine protocols to treat digestive complaints. The many bioactive ginger compounds have carminative and anti-inflammatory properties that effectively reduce abdominal symptoms. 

Demulcent herbs are those that soothe and protect irritated and inflamed tissue. Taken orally, herbs like Aloe vera, marshmallow root, and slippery elm bark can reduce mucosal inflammation of the entire intestinal tract. 

Robert's Formula is a traditional naturopathic herbal remedy that combines anti-inflammatory, demulcent, astringent, and antimicrobial herbs to treat intestinal inflammation and associated symptoms. Many variations of this formula have been created, but the original formula includes marshmallow root (Althaea officinalis), wild indigo (Baptisia australis), purple coneflower (Echinacea angustifolia), goldenseal (Hydrastis canadensis), American cranesbill (Geranium maculatum), pokeroot (Phytolacca Americana), and slippery elm (Ulmus fulva).

Alternative Treatment for Colitis

First-line treatment recommendations in any microscopic colitis protocol should include avoiding triggering medications (when possible) and counseling for smoking cessation, which can lead to the resolution of symptoms.

Intestinal infections and dysbiosis identified on stool testing should be treated. Pharmaceutical or natural antimicrobials can be implemented based on sensitivity testing and patient preference. Common antimicrobial herbs utilized by functional medicine providers include garlic, thyme, and oregano. Prebiotics and probiotics are commonly implemented in conjunction with antimicrobial therapy to increase the microbiome's beneficial bacteria, reduce intestinal inflammation, and restore intestinal barrier function.

EBV infections are commonly addressed by stress-reduction techniques, healthy nutrition, and immune-supportive herbs, including licorice, astragalus, and echinacea.

Psyllium is a soluble fiber that can be used as an alternative to prescription or over-the-counter antidiarrheal agents. Psyllium absorbs water in the digestive tract, bulking stool and making it slower to pass.

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Summary

Lymphocytic and collagenous colitis are the two subtypes of microscopic colitis, an inflammatory bowel disease that causes chronic watery diarrhea. Although serious health sequelae aren't associated with microscopic colitis, chronic diarrhea significantly impacts the quality of life when untreated. Conventional therapy, most commonly with the steroid budesonide, can induce remission in gastrointestinal symptoms, but recurrence of the disease is common once treatment is stopped. A functional medicine protocol to treat microscopic colitis aims to identify factors causing hyperstimulated immune responses responsible for gastrointestinal inflammation and commonly co-occurring autoimmune diseases. Dietary and lifestyle modifications, botanical medicine, and nutritional supplements can help to remove the obstacles to healing so that patients can achieve long-term resolution of symptoms.