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

Irritable bowel syndrome (IBS) affects around 11% of the global population. In the United States, between 25 and 45 million people, typically females under age 50, have been diagnosed with IBS. The total annual cost of IBS in the US has been estimated at upwards of $10 billion in direct medical costs and an additional $19.2 billion in indirect costs. 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 challenging symptoms of IBS on their own. 

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What Is Irritable Bowel Syndrome With Diarrhea (IBS-D)?

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 lacks observable changes to GI anatomy. 

IBS-D, affecting about one-third of IBS sufferers, is one of three IBS subtypes in which the majority of abnormal movements patients experience are described as diarrhea. 

IBS-D Signs & Symptoms

Chronic abdominal pain and diarrhea are the hallmark symptoms of IBS-D. Diarrhea is defined as loose, watery, and frequent bowel movements.

It is common for patients with IBS-D to experience other GI symptoms, too, including: 

• Gas
• Abdominal bloating and distension
• Indigestion
• Nausea
• Fecal urgency 

Root Causes of IBS-D

Although the exact cause of IBS-D is unclear, research suggests that abnormalities in gut motility, immune function, dysbiosis, and the central nervous system's interpretation of pain signals may contribute to digestive syndrome.

The microbiota-gut-brain axis has been highlighted as a central mechanism in the development and severity of IBS-D. This axis represents a bidirectional communication network linking the central nervous system, the enteric nervous system (the network of nerve cells that controls GI function), and the intestinal microbiome. Imbalances in this axis can trigger visceral hypersensitivity; in other words, the gut can become more sensitive than usual, creating abdominal pain sensations.

Dysbiosis characterized by altered composition and reduced diversity of gut microbes has been consistently observed in patients with IBS. This dysbiosis can affect gut motility, permeability, and inflammation, potentially leading to the hallmark symptoms of diarrhea and abdominal pain. (34, 49)  

The gut microbiota also influences the production of neurotransmitters such as serotonin, which helps regulate gut motility and sensitivity. Dysregulation of serotonin pathways is commonly found in IBS-D, further linking gut microbial activity to symptom manifestation. 

The gut-brain axis involves significant neuroimmune interactions. Depression and anxiety, prevalent in the IBS community, can alter gut permeability and immune responses, potentially exacerbating inflammation and dysbiosis (43). Conversely, gut microbiota can affect brain function and mood by producing metabolites that influence the central nervous system, creating a feedback loop that may perpetuate the disorder (19). 

How to Diagnose IBS-D

Diagnosing IBS-D involves a comprehensive approach that thoroughly evaluates symptoms and medical history.

Step 1: Construct a Broad Differential Diagnosis

Recent medical guidelines dictate that IBS is no longer a diagnosis of exclusion. However, because IBS-D shares symptoms with many other conditions, healthcare practitioners should perform a comprehensive evaluation to rule out alternative causes of digestive symptoms before making an IBS diagnosis. These include, but are not limited to:

• Inflammatory bowel disease (IBD): Crohn's disease, ulcerative colitis, and microscopic colitis
• Celiac disease
• Infectious gastroenteritis
• Food allergy
• Lactose intolerance
• Hyperthyroidism
• Medication side effects
• Cancer

As such, the following list of labs is appropriate to order during an initial diagnostic evaluation to rule out common GI pathologies that can masquerade as IBS-D:

• CBC w/ Diff by Access Med Labs
• Comprehensive Metabolic Panel by Access Med Labs
• Comprehensive Thyroid Panel w/ Antibodies by Precision Point
• Celiac Disease Profile by Alletess Medical Laboratory
• IgE Food Allergy Basic Test by Mosaic Diagnostics
• Lactose Malabsorption Breath Test by Commonwealth Diagnostics International, Inc.
• Stool Culture, Camp./Salm./Shig by Access Med Labs
• Stool Parasitology - 3 Day by Doctor's Data
• Calprotectin by Diagnostic Solutions

Step 2: Use the Rome IV Criteria 

The Rome IV criteria used for diagnosing IBS require that patients have recurrent abdominal pain at least one day per week during the previous three months that is associated with two or more of the following:

• Defecation
• A change in stool frequency
• A change in stool appearance

IBS is subclassified as IBS with predominant diarrhea when a patient reports most of their abnormal bowel movements are diarrhea; specifically, more than 25% are loose or watery, and less than 25% are hard or lumpy (48).  

In 2021, the Rome Foundation proposed that IBS can be diagnosed if the patient's symptoms have lasted at least eight weeks and are bothersome (i.e., interfere with daily activities, cause worry, or interfere with quality of life).

Step 3: Use Specialty Labs to Uncover the Root Causes of IBS-D

The following labs are less commonly utilized in conventional medicine algorithms but can provide valuable insight into the possible triggers contributing to IBS. 

SIBO Breath Test

Up to 80% of IBS patients have SIBO (small intestinal bacterial overgrowth). 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. 

Order one of the following tests to screen for SIBO:

• SIBO - 3 Hour by Genova Diagnostics
• SIBO/IMO Lactulose Breath Test by Commonwealth Diagnostics International, Inc.
• trio-smart SIBO Breath Test by Gemelli Biotech

Comprehensive Stool Analysis

Research has linked IBS-D to bile acid diarrhea (BAD), exocrine pancreatic insufficiency (EPI), and small intestinal fungal overgrowth (SIFO). 

Common dysbiotic patterns characteristic of IBS-D include a reduced abundance of Lactobacillus and Bifidobacterium and an increased abundance of E. coli and Enterobacter. Patients with IBS are also more likely to have parasitic infections, specifically Blastocystis, Cryptosporidium, and Giardia. (9) 

A comprehensive stool analysis provides invaluable information regarding overall gut health. The following stool tests can detect pathogenic GI infections, fungal overgrowth, and other types of large intestinal dysbiosis. Fecal elastase and bile acids can be measured in stool samples to assess for EPI and BAD.

• GI-MAP by Diagnostic Solutions
• GI360 by Doctor's Data
• GI Effects® Comprehensive Profile - 3 day by Genova Diagnostics

Food Sensitivity Testing

The majority (84%) of patients with IBS self-report food sensitivities as important triggers for their IBS symptoms. Food sensitivity panels can assist in the identification of dietary triggers so that dietary modifications can be better customized to the needs of each patient:

• IgG Food MAP with Candida + Yeast by Mosaic Diagnostics
• 96 IgG Food Sensitivity Panel by Alletess Medical Laboratory
• foodANALYZER IgG Food Sensitivity by Access Med Labs

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Treatment Plan for IBS-D

Doctors can use a step-by-step approach to help patients manage IBS symptoms while addressing the underlying factors contributing to GI function.

Step 1: Manage Symptoms

Here's Why This Is Important:

IBS, particularly IBS-D, significantly reduces health-related quality of life and work productivity due to GI symptoms.

How Do You Do This?

Treatment options for symptom relief include medications, dietary modifications, and gut-focused psychotherapy. 

The American Gastroenterological Association (AGA) recommends the following classes of medications for managing IBS-D:

• Antidiarrheals: loperamide
• Bile acid sequestrants: cholestyramine, colestipol
• Antispasmodics: hyoscyamine, dicyclomine, peppermint oil
• Antibiotics: rifaximin
• Low-dose tricyclic antidepressants: amitriptyline, desipramine

Avoiding food sensitivities based on serum IgG antibodies can help reduce IBS symptoms by 10-26%. Generally, elimination diets are considered for 4-6 weeks, followed by a food rechallenge to confirm tolerance. 

If IgG antibody testing has yet to be performed, other dietary strategies, including low-FODMAP and gluten-free diets, have been shown to help manage IBS symptoms effectively.

• FODMAPs stands for fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which are difficult-to-digest carbohydrates. Restricting FODMAPs for 2-6 weeks has been shown to help reduce pain and bloating, improve bowel habits, and improve quality of life in 75% of IBS patients. Monash University's app offers the most extensive FODMAP database, classifying foods as low, moderate, or high FODMAP with a simple traffic light system.
• Long-term adherence to a gluten-free diet may help reduce the severity of IBS symptoms and increase the likelihood of clinical remission. Grains to avoid on a gluten-free diet include barely (including malt), rye, and wheat (including kamut, semolina, spelt, and triticale).

Fiber generally helps support digestive health by improving stool consistency, supporting the growth of beneficial commensals 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.

Step 2: Address the Microbiota-Gut-Brain Axis

Why Is This Important?

The bidirectional communication between the gut microbiota and the brain significantly influences gut and mental health, impacting symptoms such as inflammation, motility, and sensitivity. Targeting this axis may increase the likelihood of long-term management without relying on medications and supplements.

How Do You Do This?

Antimicrobials may be considered to help manage unwanted (bacterial, fungal, viral, and parasitic) microorganisms in the digestive tract. Herbal antimicrobial formulas may support digestive health and, when used in combination with prescription antibiotics, can make therapy more effective and help prevent antibiotic resistance. Common ingredients found in botanical antimicrobial formulas include:

• Berberine
• Oregano
• Pau d'arco
• Thyme
• Allicin
• Caprylic acid

Probiotics are live microorganisms that may support the gut by balancing the microbiome. Two meta-analyses have shown Bifidobacterium and Lactobacillus probiotics to be safe and effective in supporting digestive health, likely by targeting the gut-brain axis to support digestion and mood self-regulation (57, 65).

Supplemental digestive enzymes provide enzymatic support when digestive enzyme insufficiency is present, contributing to malabsorption, malnutrition, food sensitivities, and gut inflammation. Patients with IBS taking digestive enzymes with meals report reduced IBS symptoms, including bloating, gas, and abdominal pain (50). Digestive enzyme formulas should be chosen based on a patient's lab findings and clinical symptoms and include one or more of the following:

• Betaine hydrochloric acid
• Pepsin
• Amylases
• Proteases
• Lactase
• Lipase
• Ox bile

Aerobic exercise has been linked to the reduction of IBS symptoms. Possible mechanisms for this include improved mental health, the promotion of nerve growth through brain-derived neurotrophic factor, modulation of the hypothalamic-pituitary-adrenal (HPA) axis, and increasing diversity in the gut microbiome. 

The Risks of Untreated IBS-D

IBS does not permanently damage the intestines or increase the risk of serious diseases, such as cancer, or mortality. 

However, living with chronic IBS-D symptoms significantly reduces overall quality of life by limiting a person's participation in social events and work productivity. This leads to increased stress, anxiety, and depression, which can further exacerbate the condition and create a vicious cycle that impacts both physical and mental health.

IBS-D Case Study

To learn more about managing IBS, read this case study:

How One Patient Found Natural Relief For Her IBS

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Key Takeaways:

• IBS-D is a chronic GI 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. By diving deeper, a comprehensive assessment can uncover the reasons behind GI imbalances that lead to IBS symptomology. A multifaceted strategy that recognizes the connection between the GI, immune, and nervous systems can profoundly transform the quality of life for those with IBS.