By Michelle Leary-Chang, ND, IFMCP
Not long ago, I had a patient present in my office proclaiming “I’m inflamed.” She described how her energy was low, she had gained 25lbs in recent years, her GI system was sluggish, and she often missed work due to unsightly skin eruptions of scalp psoriasis and acne, which made her feel embarrassed. Her issues had been chronic for over two years.
Despite several rounds of antibiotics for acne from her dermatologist, a rheumatology referral (on the waitlist), and a recent 3-day juice fast, her symptoms had progressed and led her to my Functional Medicine practice. My initial thoughts led me to an immunological workup with an emphasis on gut testing, since immune and gut function influence one another in so many ways.1-3
The term “inflammation” is a broad, catch-all term which patients often identify as being “bad” and clinicians often think of as “non-specific.” However, it is important to distinguish chronic inflammation from an acute inflammatory response.4
I needed to think broadly about what diagnostics would aid me in getting to the root cause of her health concerns.
In the context of immune system dysfunction, there can be chronic, low-level inflammation as well as acute flares of inflammation which add to an elevated homeostatic load. This particular presentation of immunoreactivity can be challenging to diagnose and treat.
When this patient requested to be tested for “inflammation,” a CRP, CBC, and ESR alone might confirm her suspicions, but would not identify the simmering source of disruption. Instead, I needed to think broadly about what diagnostics would aid me in getting to the root cause of her health concerns.
Practicing Functional Medicine means augmenting the standard of care, including conducting a basic laboratory work-up. My patient was a menstruating female with fatigue and GI disturbance. These two broad chief complaints could be separate entities, or they could be linked.5 The systems I wanted to investigate were her hematologic, endocrine, GI, and immune systems. Her initial lab work-up included:
- Thyroid panel with Anti-TPO, Anti-TG, and reverse T3
- Hs-CRP (for systemic IL-6 activation) and ESR & Fibrinogen as acute phase reactants
- Fasting insulin to assess for metabolic dysfunction
- Comprehensive metabolic panel including a liver function panel
These baseline labs were augmented with stool testing, given her gastrointestinal disturbance and recent history of antibiotic use. One may postulate that empiric treatment of gut disturbance would be adequate—and that argument certainly holds water. However, stool testing results can guide treatment for patients6-8 and I’ve found it to be instrumental with chronically inflamed patients.
Some of the specific markers commonly available through functional stool testing include:
- Calprotectin for suspicion of IBD
- Dysbiosis and Microbiome genetic analysis
- Short-chain fatty acid analytes such as butyrate and propionate
- Immunological markers such as EPX and Secretory IgA
- Pancreatic elastase enzyme
For my patient, her hsCRP was high at 3.2. She was negative for calprotectin, which significantly reduces likelihood of inflammatory bowel disease. Her stool analysis was strongly supportive of a dysbiotic system with low microbial diversity, imbalanced short-chain fatty acids, and elevated secretory IgA and EPX, both indicating immunological reactivity in the gut. What she needed was for her GI system to stop stepping on the toes of her immune system!
From a Functional Medicine perspective, the relationship between the immune and GI system is a dance.
The microbiome is highly resilient due to the frequent cellular turnover of structural cells of the GI tract,9,10 and the microbiome’s effect on gut-associated lymphoid tissue (GALT).11 In Functional Medicine, a 5-R protocol, as outlined below, is typically an initial step in supporting GI-Immune system restoration:
- Remove (bugs, drugs, inflammatory foods)
- Replace (stomach and bile acids, enzymes, amino acids)
- Reinoculate (probiotics, prebiotics, commensal yeasts)
- Repair (Nutrients, botanicals, amino acids, healthy fats)
- Rebalance (Nutrition, sleep, exercise)
Together, she and I initiated a 5-R protocol. This included a 30-day elimination diet of common immunologically reactive foods. She showed initial improvement in her mood and energy, followed by improved gut motility, scalp improvement over 6-12 weeks, and reduced frequency and severity of acne lesions. Her hsCRP dropped to normal values at a 6-month follow-up appointment. In summary, it is worthy of consideration to evaluate the GI system when suspecting immunological imbalance.
When I approach patients with inflammation, often advanced laboratory testing provides the direction needed to address the root causes of their symptoms. From a Functional Medicine perspective, the relationship between the immune and GI system is a dance. If one system is out of step, it can quickly affect the other. Advanced diagnostic labs for patients with nonspecific, lingering symptoms may include assessment of food allergies and sensitivities, cytokine profiles, complement protein testing, and further gastrointestinal testing including SIBO breath testing and toxicity analysis using provocation of urine metabolites.
When helping patients with symptoms that likely stem from a common underlying cause, these types of tests help to direct my treatment plan to achieve the best outcomes for that patient.
Michelle Leary-Chang, ND, IFMCP, is a practicing clinician in Washington state with Vida Integrated Health. In addition to her training at Bastyr University, she is also a Clinical Exercise Physiologist from the American College of Sports Medicine.
- Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2015;65(2):330-9. doi:10.1136/gutjnl-2015-309990.
- Kato LM, Kawamoto S, Maruya M, Fagarasan S. The role of the adaptive immune system in regulation of gut microbiota. Immunol Rev. 2014 Jul;260(1):67-75. doi:10.1111/imr.12185.
- Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384. 2016;Oct 21. doi:10.1080/21688370.2016.1251384.
- Pahwa R, Jialal I. Chronic Inflammation. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-.Available from: https://www.ncbi.nlm.nih.gov/books/NBK493173/
- Jungyoun Han C, Heitkemper MM, Jarrett ME. Fatigue Measures in Noncancer Gastrointestinal Disorders: A Critical Review. Gastroenterol Nurs. 2016 Nov/Dec;39(6):443-456. doi: 10.1097/SGA.0000000000000174.
- Axelrad JE, Joelson A, Nobel YR, et al. Enteric Infection in Relapse of Inflammatory Bowel Disease: The Utility of Stool Microbial PCR Testing. Inflamm Bowel Dis. 2017 Jun;23(6):1034-1039. doi:10.1097/MIB.0000000000001097.
- Arasaradnam RP, Brown S, Forbes A, et al. Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition. Gut 2018;67:1380-1399. doi:10.1136/gutjnl-2017-315909.
- Steffer KJ, Santa Ana CA, Cole JA, Fordtran JS. The practical value of comprehensive stool analysis in detecting the cause of idiopathic chronic diarrhea. Gastroenterol Clin North Am. 2012 Sep;41(3):539-60. doi:10.1016/j.gtc.2012.06.001.
- Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489(7415):220-30. doi:10.1038/nature11550.
- Darwich AS, Aslam U, Ashcroft DM, Rostami-Hodjegan A. Meta-analysis of the turnover of intestinal epithelia in preclinical animal species and humans. Drug Metab Dispos. 2014 Dec;42(12):2016-22. doi:10.1124/dmd.114.058404.
- Forchielli ML, Walker WA. The role of gut-associated lymphoid tissues and mucosal defence. Br J Nutr. 2005 Apr;93 Suppl 1:S41-8.