N of 1 for IBS recap
Part 1 : the back story
Introduction: First, before I begin this recap, I want to thank Genova Diagnostics and Gemelli Biotech (creators of Trio Smart and IBS-smart) for providing testing for this research study. Without their support, this project would not have been possible. Thank you!
In 2024, I launched the first N of 1 for IBS.
N of 1 is a term used in research to describe a study involving a single participant. This method allows precise control over variables, such as participant selection, treatment compliance, and detailed outcome monitoring. In Naturopathic and Functional Medicine, where holistic, multi-component interventions are common, an N of 1 study is particularly fitting. However, the model has inherent risks—if the participant drops out, the entire research project ends abruptly. This reflects real-life challenges in implementing comprehensive naturopathic and functional treatment protocols.
Why I decided to do the N of 1 project is a bit of a backstory in itself.
As I have interfaced with many leaders in the gastrointestinal space, I have seen these fabulous new models of digestive disorder care that include gastroenterology, gastro-directed dietitians, and gastroenterology-directed psychology. Many of the top colleagues I have interfaced with have discussed these models with me. Always left off the public stage is Naturopathic and Functional Medicine. When I confronted one of these folks on the fact that our profession is equipped to be a key component in delivering comprehensive care to digestive disorder patients, they commented: “You need to prove your model.” Anybody who knows me really well knows that that kind of challenge really lights me up.
I thought, What could be the most ideal way to treat and approach an IBS patient if resources were unlimited? I designed a protocol to be offered to one randomly selected IBS patient.
With great anticipation, I launched the selection process in the fall of 2023 and selected the candidate in December 2023.
Selection Criteria for the N of 1 Study
The criteria were based first on the legalities of me conducting bench-to-bedside research.
Location:
The participant was to live in Washington state or in states or countries where Naturopathic Physicians are not licensed. At the time of the study, this included Wyoming, Texas, Iowa, Oklahoma, Indiana, Missouri, Arkansas, Illinois, Michigan, Ohio, Tennessee, Georgia, Florida, North Carolina, Virginia, New Jersey, and New York. They were to not already be receiving care from a licensed Naturopathic Physician in their area.Insurance:
Participants could not have insurance plans that included my services as an in-network provider. This requirement avoided potential conflicts of interest and ensured that the participant was receiving care solely as part of the study.Confirmed IBS Diagnosis:
Participants must provide documentation confirming an IBS diagnosis from a gastroenterologist. This criterion ensured that the participant genuinely had IBS and met the study's focus.Primary Care Provider:
Participants must have a primary care provider they regularly see in person in their city. This stipulation ensured that the participant had access to ongoing medical care and monitoring outside the study.Media Consent:
Participants agreed to anonymous interviews and recordings with voice and video dubbing, which may be used on podcasts or YouTube channels. This requirement allowed the study team to share the participant's experiences while maintaining their anonymity.Symptom Reporting:
Participants agreed to report any new symptoms to their primary care provider under the direction of the clinic. This was a crucial safety measure to ensure that any potential adverse effects or new health concerns were promptly addressed.Limited Prescription Medications:
Participants could not be taking any prescription medications, except for PPIs (proton pump inhibitors), H2 blockers (histamine-2 receptor antagonists), or digestive aids. This criterion helped to minimize potential interactions between medications and the study interventions.Age:
Participants were to be 18 years or older. This requirement ensured that the participant was legally an adult and could provide informed consent.Pregnancy and Breastfeeding:
Participants could not be pregnant or breastfeeding. This criterion was essential for the safety of the participant and any potential fetus or nursing infant.
Note: I am not affiliated with any company or educational institution, so this was a solo project that obviously lacked some of the official processes that an Institutional Review Board (IRB) would provide. Regardless, many of the same practices were applied to this project.
Tests Conducted in the Evaluation of the Subject
The N of 1 protocol involved an evaluation process that would be considered ideal in the Naturopathic space. I looked at the need for a standardized questionnaire and functional tests that would provide a baseline of the variables involved with digestive health along with the ability effectively repeat these tests and questionnaires at measured intervals.
Digestive Wellness Questionnaire
The questionnaire was the Digestive Wellness Questionnaire (DWQ). This questionnaire has been around for many years. I first saw it through a supplement manufacturer named Integrative Therapeutics. It has been an invaluable tool for me and my patients. The questionnaire is broken down into five sections and measures symptoms of stomach lining disorders (ie. ulcers), maldigestion, small intestinal dysbiosis, intestinal permeability, and liver detoxification dysfunction. The study protocol stated that the subject would complete the Digestive Wellness Questionnaire at baseline, before the first visit, then each visit for a total of (one per month) for a year.
Organic Acid Testing (Organix)
The rationale for conducting organic acid testing in this case stems from its ability to provide insights into various metabolic processes and potential imbalances within the body. Organic acids are byproducts of metabolism, and their levels in urine can reveal valuable information about. The study used the Organix test by Genova Diagnostics.
Nutrient Deficiencies: Certain organic acid patterns can signal deficiencies in essential nutrients, such as vitamins and minerals, which can contribute to various health problems, including digestive issues.
Yeast and Fungal Overgrowth: Organic acids produced by yeast and fungi can be detected in urine, helping to identify overgrowths that may be contributing to gastrointestinal symptoms and other health concerns.
Mitochondrial Dysfunction: Mitochondria are the powerhouses of cells, and imbalances in their function can impact energy production and overall health. Organic acid testing can detect markers of mitochondrial dysfunction.
Detoxification Issues: The body's ability to detoxify harmful substances can be assessed through organic acid analysis. Inefficient detoxification can lead to the accumulation of toxins, potentially contributing to various symptoms.
In the case of IBS , the study hoped to zero in on yeast and fungal issues that often make the IBS case complex. Conditions like Small Intestinal Fungal Overgrowth (SIFO) often mimic or compound IBS or Small Intestinal Bacterial Overgrowth. Determining fungal load is helpful in the IBS patient. In addition, assessing for overall nutrient deficiency, liver, detoxification status will give insight on malabsorption, biliary function, chemical toxicant overload and other factors that often compound an IBS case.
Lactulose Hydrogen Breath / Trio-smart-Breath Test (Gemelli)
The lactulose hydrogen breath test (LHBT) is a diagnostic tool used to evaluate the presence and type of small intestinal bacterial overgrowth (SIBO) and other conditions related to intestinal dysbiosis disorders. It's a non-invasive breath test that analyzes the levels of three specific gases in a patient's breath: hydrogen (H₂), methane (CH₄), and hydrogen sulfide (H₂S). These gases are associated and known to be causal for various subtypes of IBS. For example IBS-D has been associated with a distinct pattern of Hydrogen and/or Hydrogen Sulfide production on the LHBT. Whereas, IBS-C has been associated with a distinct Methane production pattern on the LHBT. Glucose is sometimes used as a substrate on the this test instead of lactulose. I decided to use Lactulose due to many conversations and research articles that were convincing that lactulose would lead to the least false negative results.
Comprehensive Digestive Stool Analysis /GI effects (Genova)
The subject underwent a 2200 GI Effects™ Comprehensive Profile - Stool test to evaluate her digestive health and identify potential contributors to her IBS symptoms. This particular stool test is offered by Genova Diagnostics and is designed to provide a detailed assessment of various aspects of gastrointestinal function. Stool testing plays a crucial role in the evaluation and management of IBS for several reasons. It can help: Identify Underlying Causes: IBS is often diagnosed based on symptoms alone, but stool testing can uncover potential underlying causes or contributing factors that may be driving those symptoms.
The test extracts data and biomarkers of:
Infections: The presence of pathogenic bacteria, parasites, or yeast can cause or worsen IBS symptoms.
Dysbiosis: Imbalances in the gut microbiome, characterized by an altered composition of bacteria, can disrupt digestive function and contribute to symptoms like bloating, gas, diarrhea, and constipation.
Inflammation: Stool tests can measure markers of inflammation in the gut, helping to differentiate IBS from inflammatory bowel diseases (IBD) like Crohn's disease and ulcerative colitis.
Maldigestion and Malabsorption: Stool analysis can assess the efficiency of digestion and absorption of nutrients, revealing potential issues that can contribute to nutritional deficiencies and exacerbate IBS symptoms.
IBS Smart
As part of the protocol, a emmerging test called the IBS Smart was ordered. The IBS Smart test is a blood test that looks for specific antibodies associated with post-infectious IBS, a subtype of IBS thought to be triggered by a previous bout of gastroenteritis (ie food poisoning or travelers diarrhea). It's designed to help determine if a person's IBS symptoms might stem from a past infection that disrupted the gut microbiome, even if the infection itself has long since resolved.
The test measures levels of two key antibodies:
Anti-CdtB: This antibody targets a toxin (CdtB) produced by certain bacteria, such as Campylobacter jejuni, which is a common cause of food poisoning. Elevated anti-CdtB levels indicate an immune response to this toxin, suggesting a past infection with a CdtB-producing bacteria.
Anti-Vinculin: This antibody targets vinculin, a protein found in the lining of the intestines. Elevated anti-vinculin levels suggest the development of an autoimmune response, where the body's immune system mistakenly attacks its own intestinal tissues. This autoimmune reaction is thought to be triggered by the initial bacterial infection, leading to ongoing intestinal inflammation and IBS symptoms.
The IBS smart helps with the following:
Confirming Post-Infectious IBS: IBS Smart test as having a high positive predictive value (96%-100%) for diagnosing IBS. This means that if the test is positive, there's a very high likelihood that the person has post-infectious IBS..
Determining the Root Cause: Identifying post-infectious IBS as a potential cause of symptoms can help guide treatment decisions. It suggests that IBS may be rooted in a lasting disruption of the gut microbiome caused by a previous infection.
Personalizing Treatment: If the IBS Smart test confirms post-infectious IBS, it can direct treatment towards addressing the specific consequences of that past infection. This might involve:
Microbiome Restoration: Strategies to restore a healthy balance of bacteria in the gut, such as probiotics, prebiotics, and dietary changes.
Immune Modulation: Approaches to dampen the immune response and reduce intestinal inflammation if anti-vinculin antibodies are elevated, suggesting an autoimmune component.
Future evaluations: In future studies, I would likely be expanding to using Metabolomic markers that are becoming more readily available which give a good view of the overall microbiome health.
N of 1 IBS Treatment Protocol
The protocol involved several phases based on the results of the testing.
Phase 1: Initial Support and Preparation
The initial phase of treatment involved a combination of dietary guidelines and a foundational set of supplements to prepare her body for more targeted interventions in the later phases. The details of this will be discussed in the ongoing posts about this trial.
Dietary Guidelines included dietary hygeine guidance and and IBS dietary guidelines. There are common dietary hygeine guidelines that often taught in Naturopathic training which we will discuss in details and several IBS-guidelines through diet like the NHS-UK IBS Guidelines. The protocol employed a combination of dietary hygeine suggestions (ie. chewing food slowly and completely) and the NHS-UK IBS guidelines.
Based on the initial Digestive Wellness Questionnaire; a the support and preparation phase was composed based on the greatest needs. This support was provided while waiting on the implementation of the detailed testing results.
The support included categories of supplementation such as: support was in one of sev
Intestinal lining support: These supplements generally include demulcents, anti-inflammatory herbs (ie. Boswellia) , nutrients that increase intestinal integrity and gap junction function (ie. zinc), and gentle binders (ie pectin) to reduce the harmful effect of pathogen associated molecular patterns such as LPS.
Liver-gallbladder-detoxification support: Supplements in this category generally contain nutrients that help with phase 1 and phase 2 detoxification (ie. milk-thistle), antioxidant support (ie. alpha lipoic acid, N-acetyl cysteine), biliary function support (ie. artichoke extract/Cyanara scolymus leaf), and further binder support (such as chlorella) to trap toxicants mobilized by the supplement . In the IBS patient there often is biliary dysfunction that shows up on the digestive stool analysis as fat or protein malabsorption or excessive bile resistant microbes in the sample. Sometimes harmful secondary bile acids can be produces as well in certain patients. Also there is a great overlap between other conditions such as environmental toxicity, mold/mycotoxin illness, and mast cell activation syndrome with IBS so the role of the liver/gallbladder in addressing these conditions is often considered in the IBS patients. The Digestive Wellness Questionnaire and patient history will also give clues for the need for Liver/Gallbladder support in this population such as pain under the rib cage after eating fatty meals, difficulty with tolerating fatty food. headaches after eating ,light colored stool constipation , hard stool, oily skin, and acne .
Digestive enzymes. The use of digestive enzymes for IBS is common. Both from a standpoint as a palliative aid and also as a restorative aid for long term-digestive disruption. Brush Border enzymes may be low in IBS patients so restoration is is needed. In addition, biofilm formation is common in IBS patients and digestive enzyme intake can help disrupt excessive biofilm formation. Digestive enzymes fall into categories based on what their function are
For protein digestion: Bromelain, Protease I, II, III, IV , and Peptidase with or without hydrochloric acid are generally used. For Starch and Fiber digestion: Bromelain, protease, peptidase, glucoamylase, cellulase, sucrase, maltase, phytase, pectinase, lacase, alpha-galactosidases, and amylase are generally used. And For Fat Digestion; Lipase and Amylase
Motility agents/Prokinetics. In IBS, which is considered a disorder of the gut-brain-axis; we often find that motility is at the heart of the condition. The cause may be primary due to dysautonomia, brain trauma, pelvic trauma, and other conditions. Or, it can be as a result of dysbiosis and infection damaging the migrating motor complex which is responsible for the interdigestive motility of the small intestine. Regardless when we see bloating, fullness, and also constipation or any combination of these clues then it is a clue for motility support. Sometimes the support for these agents are in the form of natural laxatives such as the Ayurvedic herb Triphala and other times the support is in form of natural prokinetics like Ginger (Zingiber Officinale)
other strategies were encouraged such as mindfulness, breathing exercises, and other general mind-gut interventions but explicit treatments were not given. This would be of interest in future studies.
Phase 2: Targeted Interventions Based on Lab Findings
The lab reports and evaluations then were analyzed and layered onto the initial supportive treatment was targeted interventions based on findings including:
Addressing Dysbiosis and Potential Pathogens (with use of herbal antimicrobials and agents disruptive to overgrowth and pathogens)
Microbiome Restoration (with pre and probiotic compounds targeted to individual needs and results.
Ongoing motility support (using herbal prokinetics and other herbal motility agents)
Support was offered to mitigate side effects that may occur during this stage.
Phase 3 stabilization and prevention
Finally, the treatment protocol main portion was intended for 3-6 months with a transition based on clinical response to a stabilization and prevention protocol with included:
prevention of recurrence and stabilization through ongoing dietary, lifestyle, nutritional, probiotics, mind-body, and herbal intervention.
Since preventing IBS flares and reoccurrence at this time is a lifestyle and dietary practice this was a major emphasis of this phase.
All supplements were provided at no cost to the participant through the entire treatment protocol.
So, the stage was set for a comprehensive trial.
The subject was selected
Baseline labs and assessments were collected
Treatment protocols were assigned.
In the next post we will learn about the details of our participant, their test results and interpretation, and start discussing their response to the trial. I welcome questions below in the chat area. Also, please subscribe to our newsletter and consider becoming a paid subscriber to continue to fund my personal research, writing, and podcasts that enhance my offerings as a clinician and health educator.