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A Functional Medicine IBS-D Protocol: Testing, Differential Diagnosis, and Treatment

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A Functional Medicine IBS-D Protocol: Testing, Differential Diagnosis, and Treatment

Irritable bowel syndrome (IBS) affects 5-10% of the global population. In the United States, IBS is responsible for afflicting an estimated 25-45 million people, typically females under 50. Annually in the United States, IBS accounts for 2.4-3.5 million physician visits and 20-40% of specialty gastroenterologist visits. Despite these high numbers, less than half of IBS sufferers seek medical care; this means that many are left without the necessary medical support and are faced with dealing with the unpredictable and debilitating symptoms of IBS on their own. (1, 2)  

This article will discuss a subset of IBS called IBS-D. After discussing the etiology of the disease, the article will discuss considerations for an integrative approach to diagnosis and treatment, providing a sample protocol that can be utilized in clinical practice.


What is IBS-D?

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID) characterized by chronic abdominal pain and disruptions in gastrointestinal (GI) function that cannot be explained by another diagnosis and lack observable changes to GI anatomy. IBS-D is an IBS subtype affecting about one-third of IBS sufferers. With IBS-D, at least 25% of abnormal bowel movements accompanying abdominal pain are characterized as diarrhea, or loose and/or frequent stools.

IBS-D Symptoms

Abdominal pain occurring at least once weekly and chronic diarrhea are the hallmark symptoms of IBS-D. IBS-D can present with other GI symptoms, such as abdominal bloating, increased satiety, indigestion, nausea, gas, and fecal urgency. (3)

What Causes IBS-D?

Although the exact cause of IBS-D is unclear, research points to abnormalities in gut motility, immune dysfunction, microfloral dysbiosis, and the central nervous system's misinterpretation of pain signals as contributing factors to this digestive syndrome.

The gut-brain axis is the bidirectional communication speedway between the digestive tract and the brain. Imbalances in this axis can trigger visceral hypersensitivity; in other words, the gut can become more sensitive than usual, creating abdominal pain sensations.

The trillions of microorganisms in the gut make up the intestinal microbiome. Interruptions in the microbiome's healthy balance, including dysbiosis, small intestinal bacterial overgrowth (SIBO), and GI infection, may alter intestinal motility and set off inflammatory immune reactions.

Differential Diagnosis for IBS-D

Because IBS-D shares symptoms with many other conditions and diseases, the practitioner should perform a comprehensive evaluation to rule out alternative causes of digestive symptoms before making an IBS diagnosis.

Bile acid diarrhea (BAD, or bile acid malabsorption) occurs when bile is not reabsorbed in the small intestine and flows into the large intestine. Up to one-third of patients with IBS-D may have bile acid diarrhea of unknown cause.

People with IBS-D are more likely to have a disorder called exocrine pancreatic insufficiency (EPI), in which the pancreas produces insufficient levels of digestive enzymes. One study found that 6.1% of patients with IBS-D have EPI.

Reactions to foods like FODMAPs, gluten, and dairy may irritate the gut lining, impairing intestinal motility and creating hyperstimulated immune responses (4-6). Celiac disease is an autoimmune attack of the small intestine in response to gluten exposure. Non-celiac gluten sensitivity (NCGS) is a non-autoimmune sensitivity to gluten. Lactose intolerance is caused by a deficiency in the lactase enzyme, impairing the body's ability to digest and absorb lactose in dairy products. All three conditions can cause GI symptoms that appear similar to IBS-D.

Studies have established that people with IBS have significantly different microbiome profiles than people without. IBS-D sufferers are ten times more likely to suffer from hydrogen-predominant SIBO, which occurs when hydrogen-producing bacteria overgrow in the small intestine (1). Research also indicates that small intestinal fungal overgrowth (SIFO) may present in 25% of patients with unexplained IBS symptoms.

More than 40% of patients with inflammatory bowel disease (IBD) present with IBS symptoms. IBD is a group of inflammatory conditions, encompassing ulcerative colitis, Crohn's disease, and microscopic colitis, that causes chronic and potentially life-threatening inflammation within the GI tract.

Dysthyroidism, including overactive and underactive thyroid states, can negatively affect GI health and function, increasing the risk of celiac disease, intestinal bacterial overgrowth, and IBS-D symptoms (7).

Studies show that stress, anxiety, and IBS occur together, although it's unclear which one comes first. It is estimated that 60% of IBS patients will meet the criteria for one or more psychiatric disorders, most commonly anxiety and depression. (8)

Functional Medicine Labs to Test for the Root Cause of IBS-D

The diagnosis of IBS-D is made by using the ROME IV criteria and ruling out other conditions with similar presenting symptoms. While standard labs and imaging, such as CBC, CMP, and colonoscopy, are beneficial in ruling out GI pathology, they typically result in normal results. Functional medicine labs go beyond standard screening protocols to assess factors often overlooked in a conventional workup, allowing a more detailed evaluation of IBS-D.

Comprehensive Thyroid Panel

In a conventional setting, thyroid disease is typically screened for using TSH alone, which can miss up to 7% of thyroid dysfunction. A complete thyroid panel, which includes TSH, free T3 and T4, total T3 and T4, reverse T3, and thyroid antibodies, provides more data points in understanding the thyroid axis and recognizing subclinical and overt hypo- and hyperthyroidism.

Comprehensive Gut Assessment

A comprehensive stool analysis provides invaluable information regarding overall gut health. This test can detect pathogenic GI infections, fungal overgrowth, and other types of large intestinal dysbiosis. Functional stool analyses also measure intestinal inflammatory markers like calprotectin and lactoferrin, often elevated in active IBD and celiac disease. Fecal elastase and bile acids can be measured in stool to assess for EPI and BAD.

SIBO Breath Test

Up to 80% of IBS patients have SIBO. A SIBO breath test measures various gas levels produced in the small intestine and exhaled through the breath. Elevations in hydrogen gas levels of at least 20 ppm by 90 minutes are diagnostic of hydrogen-predominant SIBO, most commonly associated with IBS-D.

Food Sensitivities

Food sensitivities, intolerances, and allergies may play a role in GI symptoms for some people with IBS. Food sensitivity and allergy panels can assist in the identification of dietary IBS triggers. Lactose intolerance is diagnosed with a breath test. A wheat sensitivity panel measures various immune proteins and genetic markers that can help to support a diagnosis of celiac disease or NCGS.

Conventional Treatment for IBS-D

The goal of conventional treatment of IBS-D is to provide symptom relief. A typical conventional protocol includes lifestyle modifications (e.g., sleep, exercise, stress management), dietary modifications (e.g., fiber supplementation and low-FODMAP diet), and pharmaceutical medications. The most common medications prescribed for managing IBS-D include antidiarrheals, antispasmodics, low-dose antidepressants, and antibiotics.

Functional Medicine Treatment Protocol for IBS-D

While conventional treatment approaches are appropriate for symptomatic relief, they often don't address underlying factors contributing to IBS-D severity. A functional medicine treatment protocol uses functional lab findings to personalize treatment to the patient's physiologic needs. Treatment plans for IBS-D will often consist of dietary modifications, supporting digestion, reducing stress with mind-body techniques, correcting microbial imbalances, and slowing down gut motility.

Therapeutic Diet and Nutrition Considerations for IBS-D

Because adverse food reactions are so common in patients with IBS, dietary therapy is almost always a component of an IBS treatment plan. An elimination diet is strongly encouraged for IBS patients, especially if food reactions are suspected or testing reveals positive results. Generally, an elimination diet is followed for four to six weeks before the patient rechallenges foods back into the diet.

Like conventional doctors, functional medicine providers often recommend a low FODMAP elimination diet, which can be modified to accommodate specific food sensitivities/allergies. FODMAPs stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which are difficult-to-digest carbohydrates and can exacerbate SIBO symptoms. Restricting FODMAPs for 2-6 weeks has been shown to reduce pain and bloating, improve bowel habits, and improve quality of life in 75% of IBS patients.

Fiber generally helps relieve IBS symptoms by improving stool consistency, supporting the growth of Lactobacillus and Bifidobacterium, and interacting with the nervous system to decrease pain signals. Most people do not meet the recommended minimum of 25 grams of dietary fiber daily. Non-fermentable fibers, such as psyllium, oats, and partially hydrolyzed guar gum, are usually best tolerated by those with IBS.

Supplements Protocol for IBS-D

Incorporating dietary and herbal supplements into an IBS-D treatment protocol can help patients achieve desired health outcomes more quickly than with dietary and lifestyle modifications alone. Below is a sample protocol of commonly recommended gut-supportive supplements by functional medicine doctors.

Digestive Enzymes

Various digestive enzyme formulas are available to provide enzymatic support when digestive enzyme insufficiency is present, contributing to malabsorption, malnutrition, food sensitivities, and gut inflammation. Digestive enzyme formulas should be chosen based on a patient's lab findings and clinical symptoms. Popular formulas include one or several of the following ingredients: betaine hydrochloric acid, pepsin, amylases, proteases, lactase, lipase, and ox bile. Research has shown reduced IBS symptoms, such as bloating, gas, and abdominal pain, in IBS patients taking digestive enzymes (9, 10).

Dose: one serving size (per label) at the beginning of each meal

Duration: 3-12 months


Antimicrobials may be needed to remove unwanted (bacterial, fungal, viral, and parasitic) microorganisms from the digestive tract. Herbal antimicrobial formulas are just as effective as the prescription antibiotic rifaximin in treating SIBO and, when used in combination with prescription antibiotics, can make therapy more effective and prevent antibiotic resistance. (11)

Biocidin® by Biocidin Botanicals combines 18 antimicrobial extracts and essential oils to target the entire GI tract and restore a healthy balance of microorganisms within the microbiome.

Dose: 2 capsules three times daily

Duration: 6-12 weeks

Zenbiome™ DUAL

Probiotics are live microorganisms that support the gut by balancing the microbiome. Two meta-analyses have shown Bifidobacterium and Lactobacillus probiotics to be safe and effective in treating IBS (12, 13). Zenbiome™ DUAL is a probiotic by Microbiome Labs that combines two strains of Bifidobacterium longum. It targets the gut-brain axis, supporting digestion and mood self-regulation.

Dose: 2 capsules daily

Duration: 3-6 months


Carminative and spasmolytic herbs are those that help to break up intestinal gas and soothe muscular contractions. The most popular of these herbs in the context of IBS-D is peppermint. This meta-analysis concluded that enteric-coated peppermint oil is a safe and effective therapy for IBS management. STW5 (IberogastⓇ) is a safe and effective herbal formula containing nine botanical extracts for treating FGIDs, including IBS. Symptom relief is attributed to this formula's spasmolytic and anti-inflammatory effects. (8, 9)

Dose: 20 drops three times daily

Duration: Ongoing/As needed

When to Retest Labs

While it is common for patients to experience symptom changes within days to weeks of starting a functional treatment plan, substantial changes to gastrointestinal foundations require time. Therefore, it is generally recommended to postpone reordering functional medicine labs anywhere from 3-12 months after starting a plan. It may be necessary to reassess some labs, like thyroid hormones, sooner than this. The testing frequency should be determined based on each individual's case, baseline lab results, and preferences.



IBS-D is a chronic gastrointestinal condition that causes mild to severe abdominal pain and diarrhea. Left untreated, IBS-D poses a significant risk to a person's quality of life. Unfortunately, conventional medications do not always manage IBS symptoms, leading people to seek alternative care options.

IBS can be difficult to diagnose and manage because many conditions have overlapping symptoms. Functional labs can help expedite the diagnostic process by including biomarkers that aren't typically a part of the standard diagnostic process. By diving deeper, a comprehensive assessment can uncover the reasons behind GI imbalances leading to IBS symptomology. As discussed in this article, functional medicine approaches can be implemented, customized to an individual's needs, for improved health outcomes.

The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.
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Lab Tests in This Article

1. Henry, K. (2022, October 31). IBS vs IBD: Know The Symptoms. Rupa Health.

2. Khakham, C. (2023, May 23). A Comprehensive Review of IBS-D: Differential Diagnosis, Specialty Testing, and Integrative Treatment Options. Rupa Health.

3. IFFGD. (2022, April 1). Subtypes of IBS - About IBS. International Foundation for Gastrointestinal Disorders.

4. Gibson, P.R., & Shepherd, S.J. (2010). Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. Journal of Gastroenterology and Hepatology, 25(2), 252–258.

5. Catassi, C., Alaedini, A., Bojarski, C., et al. (2017). The Overlapping Area of Non-Celiac Gluten Sensitivity (NCGS) and Wheat-Sensitive Irritable Bowel Syndrome (IBS): An Update. Nutrients, 9(11).

6. Deng, Y., Misselwitz, B., Dai, N., et al. (2015). Lactose Intolerance in Adults: Biological Mechanism and Dietary Management. Nutrients, 7(9), 8020–8035.

7. Daher, R., Yazbeck, T., Jaoude, J.B., et al. (2009). Consequences of dysthyroidism on the digestive tract and viscera. World Journal of Gastroenterology, 15(23), 2834.

8. WebMD. (2004, May 12). Stress, Anxiety and Irritable Bowel Syndrome. WebMD.

9. Spagnuolo, R., Cosco, C., Mancina, R.M., et al. (2017). Beta-glucan, inositol and digestive enzymes improve quality of life of patients with inflammatory bowel disease and irritable bowel syndrome. European Review for Medical and Pharmacological Sciences, 21(2 Suppl), 102–107.

10. Ciacci, C., Franceschi, F., Purchiaroni, F. et al. (2011). Effect of beta-glucan, inositol and digestive enzymes in GI symptoms of patients with IBS. European Review for Medical and Pharmacological Sciences, 15(6), 637–643.

11. Cloyd, J. (2023, April 20). Antibiotics 101: What You Need To Know. Rupa Health.

12. Yuan, F., Ni, H., Asche, C.V., et al. (2017). Efficacy of Bifidobacterium infantis 35624in patients with irritable bowel syndrome: a meta-analysis. Current Medical Research and Opinion, 33(7), 1191–1197.

13. Tiequn, B., Guanqun, C., & Shuo, Z. (2015). Therapeutic Effects of Lactobacillus in Treating Irritable Bowel Syndrome: A Meta-analysis. Internal Medicine, 54(3), 243–249.

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