How leaky gut and dysbiosis in musculoskeletal problems is being increasingly recognized via nutrition testing
The role of nutrition testing in diagnosing and treating musculoskeletal conditions isn’t an intuitive one. After all, we usually think of nutritional testing in terms of managing digestive issues, food sensitivities, and leaky gut syndrome, not as a cause of lower back pain or aching knees. Based on the latest research into increased intestinal permeability and the role of the gut microbiome, however, it’s time to expand our thinking and understand the significant value nutritional testing provides for our patients with musculoskeletal issues.
The gut’s role in inflammation
Muscle aches and painful joints can often be traced back to systemic inflammation that originates in the gut. Let’s start with the fact that today about 75% of all Americans are overweight or obese, conditions that cause systemic inflammation from the overproduction of inflammatory mediators that include IL-6, IL-8, and TNF-alpha. The metabolic syndrome, prediabetes, and type 2 diabetes are so prevalent that only a small minority (about 12%) of adult Americans are metabolically healthy.
The Standard American Diet (SAD) is the root cause of the massive overweight and obesity numbers. The SAD is a major contributor to why 72% of all Americans report they have experienced GI symptoms such as heartburn, nausea, gas, bloating, or diarrhea a few times a month or more. But the SAD does far more damage than just occasional heartburn. It damages the lining of the gut, notably the lining of the small intestine, which leads to increased intestinal permeability.
The longest part of your digestive system, your small intestine, is on average about 22 feet long, only an inch in diameter, and has a lining with the thickness of a wet paper towel. The small intestine is tightly wrinkled into many circular mucosal folds to increase the absorptive area. Each fold has thousands of tiny, fingerlike projections called villi; one square inch of the small intestine contains around 20,000 villi. Each villi has thousands of even more microscopic projections called microvilli. The folds, villi, and microvilli all increase the surface area of the small intestine — when spread out, your small intestine has the surface area of a tennis court up to a basketball court.
The villi and microvilli are made of a thin, flat layer of epithelial cells held together very tightly at the junctions where they meet — they resemble subway tiles on a wall. Properly functioning tight junctions open up just enough to let molecules of digested nutrients through them. This “intestinal permeability” is regulated by zonulin, a protein synthesized in intestinal and liver cells. Zonulin was discovered in 2000 by Alessio Fasano and his team at the University of Maryland School of Medicine.
Nutrition testing and leaky gut syndrome
When the small intestine is stressed or damaged, the tight junctions may open too widely, allowing larger molecules of undigested food, bacteria, and toxins to enter the bloodstream inappropriately. This faulty functioning of the junctions causes gut hyperpermeability or increased intestinal permeability, better known as leaky gut syndrome. Think of the tight junctions as a screen door that should only let air through. When the screen openings are too large, or the screen has holes, flies and mosquitoes can get through.
The leaky gut syndrome has many causes; some of the most common culprits are:
- Celiac disease and gluten sensitivity
- A wide range of food sensitivities
- Acid-blocking drugs
- Heavy metal exposure
- Food allergies
- Environmental toxins
- Yeast/bacteria overgrowth
Two factors that trigger zonulin release are exposure to pathogenic bacteria and exposure to gluten. By increasing intestinal permeability when pathogenic bacteria are present, zonulin may help flush them from the system. However, the damage this does to the intestinal barrier may lead to leaky gut syndrome and may be an underlying cause of allergies, inflammation, and autoimmune disease.[i]
People with celiac disease have been shown to have elevated zonulin levels. Because modern wheat has been bred to contain high levels of gliadin, one of the proteins in gluten, today many people are sensitive to gluten when in earlier times they would have had no problem. By some estimates, between 30-50% of the population is affected by non-celiac gluten sensitivity.[ii]
Zonulin is also elevated in individuals with non-celiac gluten sensitivity. Elevated zonulin is also found in several autoimmune diseases and is a contributing cause of type 1 diabetes.[iii]
Other food sensitivities can damage the intestinal barrier and cause leaky gut syndrome. Conversely, leaky gut syndrome can lead to multiple gut issues, especially food sensitivities. Damage to the gut epithelial barrier from the SAD and exposure to the many environmental toxins and chemicals in use today may be the primary reason for the sharp increase in allergies, autoimmunity, and other chronic conditions over the past few decades.[iv]
When undigested food particles, bacteria, toxins, and other substances escape the small intestine, they encounter the immune system in the gut-associated lymphoid tissue (GALT) that surrounds the gut. Some bacteria and other substances routinely escape the small intestine, and the GALT efficiently neutralizes them. When the tight junctions are compromised, they may allow large amounts of these substances to enter into the circulation, activating the rest of the immune system. The result is localized and systemic inflammation.
In addition to a systemic inflammatory response, food sensitivities can cause or exacerbate musculoskeletal conditions, including joint pain, low back pain, muscle pain, and tightness. Gastrointestinal symptoms include gas, abdominal cramps, bloating, and constipation. Rashes, fatigue, and brain fog are other common symptoms.
The gut microbiome and inflammation
The hundred trillion or so of bacteria and other microorganisms typically found in the gut are collectively known as the gut microbiome. The bacteria in the gut are essential for breaking down fiber and undigested food particles when they arrive in the colon.
Gut bacteria’s metabolic byproducts (metabolites) include short-chain fatty acids (SCFAs), particularly butyrate. In addition to fueling the epithelial cells that line the colon, SCFAs play an essential role in modulating systemic inflammation and autoimmunity.
The low-fiber Standard American Diet, antibiotic use, illness, alcohol use, and several other factors can lead to dysbiosis or an imbalance in the gut microbiome. In addition to the digestive problems dysbiosis can cause, an unbalanced microbiome means bacterial metabolites include more inflammatory cytokines such as TNF-alpha, IL-1, and IL-6. These enter the circulation and contribute to systemic inflammation.
In addition, leaky gut syndrome and/or gut dysbiosis leads to the overexpression of matrix metalloproteinases (MMPs), a group of enzymes that degrade most extracellular matrix proteins during normal tissue turnover. When MMPs production is upregulated, it damages the collagen and causes tissue remodeling associated with cartilage degradation, arthritis, and intervertebral disc degeneration.
The gut-bone axis
The role of leaky gut and dysbiosis in musculoskeletal problems is being increasingly recognized. The crosstalk between the gut microbiome and the joints, for example, can be an underlying cause of osteoarthritis. In people inflamed for other reasons, including obesity, age, and poor diet, inflammation from dysbiosis may be the final factor that causes joint inflammation. Dietary changes to improve dysbiosis and resolve leaky gut are often helpful for reducing joint inflammation.[v]
Another excellent example of the gut-bone axis is the role of the gut in intervertebral disc degeneration and low back pain. A growing body of research links increased gut permeability and dysbiosis to degenerative processes in the spine, such as those that cause low back pain. For example, in the case of intervertebral disc disease, one potential mechanism is the translocation of bacteria across the gut epithelial barrier and into the intervertebral disc, where they cause inflammation and degenerative damage. Another possible mechanism is systemic inflammation from increased gut permeability and dysbiosis added to existing inflammation from older age, obesity, and poor diet. Yet another potential mechanism is diffusion of inflammatory gut metabolites into the intervertebral disc.[vi]
As a final example, about half of all people with spondylarthritis, a group of related disorders that includes ankylosing spondylitis and psoriatic arthritis, have gut inflammation. Chronic gut inflammation predicts a higher risk of worsening disease among these patients. Reducing their gut inflammation leads to remission of joint disease — and vice versa. Therapies that simultaneously target inflammation in the gut and the joints are often beneficial.[vii]
The value of nutrition testing
Dietary and lifestyle changes that reduce systemic inflammation are highly effective for relieving musculoskeletal pain. Their effectiveness can be increased when we can make specific recommendations for dietary changes that eliminate tested food sensitivities via nutrition testing.
Because food allergies cause immediate and apparent reactions to even a small dose, the exact cause with nutrition testing can be easily diagnosed. However, food sensitivities are tough to diagnose due to their delayed nature; it typically takes up to 72 hours before the presentation of symptoms after ingestion of food. In addition, a wide range of foods can cause sensitivity reactions, and a patient is likely to be reactive to more than one. Tracing food sensitivity symptoms back to a specific food can be frustratingly difficult. The link between an aching joint three days after eating a reactive food isn’t usually obvious.
Convenient and accurate nutrition testing reveals food sensitivities. Modern methods use blood spots and serum to detect IgG (1-4) responses to a broad array of food proteins and food additives. The testing can reveal sensitivities to approximately 176 different foods and food additives and characterize them by the degree of severity. To make the results even more accurate, the test also measures immune complexes, the most common food-related pathways in the body. Immune complexes resulting in inflammation are underlying causes for many musculoskeletal conditions.
Implementing patient test results
Based on the nutrition testing results, patients learn which foods must be temporarily eliminated from the diet and which can be eaten liberally. After treatment for increased intestinal permeability, re-testing can tell us which reintroduced foods still cause a reaction and should continue to be avoided. The nutrition testing makes the reintroduction process much more effective for the patient.
When zonulin testing is added to IgG testing, the results are even more valuable. Until this testing became available, practitioners diagnosed leaky gut syndrome based on patient reporting of symptoms such as gas, brain fog, and muscle and joint pain. The effectiveness of treatment similarly relied on subjective reporting of symptom improvement and sometimes led to prematurely ending treatment, only to have symptoms return.
Today, zonulin testing reveals blood levels of zonulin antibodies for an accurate assessment of intestinal permeability. Elevated zonulin levels are associated with celiac disease, multiple sclerosis, and a range of inflammatory autoimmune diseases. Zonulin testing can confirm celiac disease and gluten sensitivity and can act as an early warning of potential autoimmune diseases such as rheumatoid arthritis.
Measuring treatment effectiveness
Zonulin testing is valuable for assessing the effectiveness of treatment. In the case of celiac disease and gluten sensitivity, for example, removing gluten from the diet decreases zonulin levels. Repeated testing shows when baseline barrier function in the small intestine has been restored and the intestinal damage has healed, allowing the patient to resume a normal gluten-free diet.
Similarly, repeated zonulin testing can indicate how well leaky gut syndrome treatment from other causes is proceeding. The results can help adjust the treatment and assess patient compliance with the needed dietary restrictions. Because resolving leaky gut syndrome is a slow process that can take several months, testing that shows improvement in zonulin levels helps encourage patients to stay with the treatment plan.
With nutrition testing, patients appreciate the convenience of just one test for food sensitivities, inflammation, and gut permeability. Practitioners appreciate the clarity the results provide for deciding on the best approach to treatment.
Protocol for low back pain
The current literature on the correlation between gut and musculoskeletal conditions supports a combined treatment approach. My approach uses my seven-step protocol for treating gut inflammation and my supplement protocol for treating low back pain.
My Super 7(R) Action Plan for the gut can be beneficial for relieving a range of gut problems and restoring the intestinal barrier:
- Reset diet/lifestyle/mindset.
- Remove pathogens and food sensitivities. Remove pathogens with oregano oil, berberine, garlic, and serum-bovine immunoglobulin.
- Replaced needed digestive enzymes and stomach acid and improved bile flow with betaine HCI and pepsin with ox bile or taurine.
- Regenerate damaged intestinal mucosa. A plethora of nutrients can be used to create an anti-inflammatory status in the gut and stimulate mucosa healing.
- Re-inoculate with quality prebiotics and probiotics.
- Reintroduce/retest foods removed in step 2 or use nutrition testing for food sensitivities at this point.
- Retain your health and gut integrity.
Improving gut health can go a long way toward also improving musculoskeletal problems. Adding a targeted protocol of daily supplements helps relieve musculoskeletal inflammation and reduces intervertebral disc degeneration:
- Omega-3 fatty acids with an EPA/DHA ratio of 2:1; 4 to 6 grams daily
- Vitamin D3 (5,000 mg) with vitamin K2 (50 mg), daily
- Glucosamine (1,500 mg) and chondroitin sulfate (1,200 mg), daily
- MSM (methylsulfonylmethane) 1 gram, daily
- Hyaluronic acid 100 mg, daily
If your gut is healthy, your musculoskeletal system is healthy. As Confucius said, “A healthy man wants a thousand things; a sick man only wants one.”
ROBERT G. SILVERMAN, DC, DACBN, DCBCN, MS, CCN, CNS, CSCS, CIISN, CKTP, CES, HKC, FAKTR, is a chiropractic doctor, clinical nutritionist, national/international speaker, author of Amazon’s #1 bestseller “Inside-Out Health,” and founder and CEO of Westchester Integrative Health Center. He graduated magna cum laude from the University of Bridgeport College of Chiropractic and has a Master of Science degree in human nutrition. The ACA Sports Council named him “Sports Chiropractor of the Year” in 2015. He is on the advisory board for Functional Medicine University and is a seasoned health and wellness expert on the speaking circuits and in the media. A frequently published author in peer-reviewed journals and other mainstream publications, he is a thought leader in his field and practice. His new book, “Superhighway to Health,” was published in June 2021. He can be reached at drrobertsilverman.com.
[i] Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. doi: 10.1152/physrev.00003.2008. PMID: 21248165
[ii] Dr. Rodney Ford, The Gluten Syndrome: Is Wheat Causing You Harm? (2008).
[iii] Sapone A et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006 May;55(5):1443-9. doi: 10.2337/db05-1593. PMID: 16644703.
[iv] Akdis CA. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity, and other chronic conditions? Nat Rev Immunol. 2021 Nov;21(11):739-751. doi: 10.1038/s41577-021-00538-7. Epub 2021 Apr 12. PMID: 33846604.
[v] Li Y, Luo W, Deng Z, Lei G. Diet-Intestinal Microbiota Axis in Osteoarthritis: A Possible Role. Mediators Inflamm. 2016;2016:3495173. doi:10.1155/2016/3495173
[vi] Li W, Lai K, Chopra N, Zheng Z, Das A, Diwan AD. Gut-disc axis: A cause of intervertebral disc degeneration and low back pain? Eur Spine J. 2022 Mar 14. doi: 10.1007/s00586-022-07152-8. Epub ahead of print. PMID: 35286474.
[vii] Asquith M, Elewaut D, Lin P, Rosenbaum JT. The role of the gut and microbes in the pathogenesis of spondyloarthritis. Best Pract Res Clin Rheumatol. 2014 Oct;28(5):687-702. doi: 10.1016/j.berh.2014.10.018. Epub 2014 Nov 15. PMID: 25488778; PMCID: PMC4293151.