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The Microbiome-Joint Axis: Exploring the Gut's Influence on Joint Pain

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The Microbiome-Joint Axis: Exploring the Gut's Influence on Joint Pain

Did you know the joint pain you're experiencing could be related to the health of your gut? Over 50 million Americans experience chronic pain, and almost 60 million adults have been diagnosed with arthritis. Conventional approaches to chronic pain often lack efficacy, and many are left taking pain-relieving medications daily to manage symptoms.

Intestinal dysbiosis is known to contribute to systemic inflammation and joint pain. Additionally, more research is coming out to support dysbiosis as a contributing factor to metabolic conditions like obesity and type 2 diabetes, which further increase the risk of pain. A functional medicine approach to achieve pain relief includes comprehensive evaluation and treatment of the gut to dampen immune hyperactivity and pro-inflammatory responses stemming from gastrointestinal imbalances.


What is the Gut's Role in Joint Pain?

The gut and joint pain are related through a complex interaction known as the gut-joint axis. The gut plays an important role in regulating the body's immune response, and it has been suggested that disruptions to the gut microbiome can contribute to the development of autoimmune disorders, inflammation, and pain that affect the joints. The following culprits have been extensively studied.

Western Diet

The Western diet (also referred to as the Standard American Diet, or SAD) is low in fruits and vegetables and high in unhealthy fats, sugar, and sodium. Furthermore, large portions of processed, nutrient-poor foods exacerbate common nutrient deficiencies afflicting the majority of the American population. Plenty of evidence supports that the poor quality of SAD does not support optimal wellness and amplifies lower immune function and systemic inflammation (1, 2).

Dietary influence on autoimmune and arthritic conditions has been widely studied. Rheumatoid arthritis (RA) is an autoimmune disease that causes joint pain, swelling, and erosion. RA is more prevalent in Western countries than the rest of the world, where dietary intake is characterized by high intakes of poor-quality red meat, saturated/trans fats, low ratios of omega-3:omega-6 fatty acids, and high consumption of refined carbohydrates. These dietary patterns have been associated with an increased risk of RA due to their pro-inflammatory qualities and increased association with obesity and insulin resistance.

Almost 42% of American adults are obese. Increased body mass index (BMI) and obesity are known risk factors for soft tissue and joint damage, commonly contributing to arthritis and exacerbating the severity of associated joint pain. Modest weight loss through dietary and lifestyle modifications, among other therapeutic interventions, can limit arthritis progression and improve activity levels.


A healthy gut microbiome is essential in regulating the immune system and normal inflammatory responses. The gut houses 70% of the immune system. The immune system and the gut microbiome are intimately connected; immune cells and gut microbes constantly communicate to influence body function. Changes in microbiome composition impact immune function, and specific dysbiotic patterns can promote pro-inflammatory immune responses. Understanding this, it's no wonder that dysbiosis has been implicated in the development of multiple forms of inflammatory arthritis. (3, 4)

Furthermore, a healthy gut-brain connection requires a healthy microbiome. More research is emerging that clarifies the relationship between the microbiome and chronic pain. The trillions of bacteria in our gut produce signaling molecules, including neurotransmitters. In fact, 90% of serotonin is made by the microbiome. Dysbiosis can interfere with neurotransmitter synthesis and trigger neuroinflammation, negatively influencing how the nervous system sends and perceives pain signals.

Intestinal dysbiosis can also directly stimulate gut "leakiness" by inducing increased production of zonulin, an intestinal protein that increases the permeability of the intestinal barrier. Joint pain and arthritis are common manifestations of a leaky gut because of the exaggerated pro-inflammatory immune activation resulting from intestinal permeability. Lipopolysaccharide (LPS) is a bacterial-derived toxin frequently measured in dysbiotic states, leaky gut, and chronic inflammatory conditions.

Food Sensitivities

Food sensitivities can both cause and result from a leaky gut. Food sensitivities are different than food allergies, although both are immune-mediated. Food sensitivities occur when the immune system recognizes food proteins as foreign and mounts an IgG-mediated response. Symptoms related to food sensitivities can occur hours to days after ingesting the trigger food(s) and are not always limited to the gut. Common symptoms indicative of food sensitivity include abdominal pain, changes in bowel movements, joint pain, fatigue, and skin rashes.

Food allergies are potentially life-threatening IgE-mediated immune responses that occur immediately after eating the allergen. Although less research supports the connection between food allergies and joint pain, unidentified food allergies can contribute to immune dysregulation, autoimmune responses, and chronic pain.

Micronutrient Deficiencies Due to Inflammation

Joint pain is a common extraintestinal manifestation of inflammatory and functional gastrointestinal disorders. Chronic intestinal inflammation, as seen in conditions like celiac disease and IBD, can impair normal digestive processes, leading to malabsorption and micronutrient deficiencies. Low levels of nutrients are commonly measured in people experiencing chronic pain, including vitamin D, B vitamins, omega-3 fatty acids, magnesium, zinc, iron, and selenium. (5)

Functional Medicine Labs to Test for Joint Pain Due to Poor Gut Health

Food Sensitivities

Food sensitivities can be identified by measuring the concentration of immune antibodies against particular food proteins the immune system reacts to. IgA and IgG-immune mediated reactions are the most common adverse immune reactions associated with joint pain. IgE-mediated food allergies can also be diagnosed through blood testing. Many labs offer combined panels that measure all three antibody types for efficiency. Blood spot test versions are also available for convenient at-home sample collection or for patients averse to blood draws.

Gut Analysis

The Array 2 panel measures antibodies to lipopolysaccharide (LPS), occludin/zonulin, and the actomyosin network. Elevated antibodies indicate a leaky gut stimulating exaggerated immune responses and systemic inflammation. For accurate results, it is recommended that patients discontinue steroid medications for 60 days before testing.

Patients with joint pain and other symptoms of inflammatory gastrointestinal diseases (i.e., celiac disease, IBD) should be referred for gastrointestinal imaging to confirm. Blood tests that measure antibodies associated with celiac disease, non-celiac gluten sensitivity (NCGS), and gluten-related autoimmunity can help in the diagnostic process.

Comprehensive stool testing is a helpful tool for broadly investigating gut health. Stool analyses can provide a myriad of valuable information regarding digestion and absorption of food, intestinal inflammation, and the gut microbiome. Zonulin can be added to most comprehensive stool tests to screen for leaky gut.

Inflammatory Markers

Measuring inflammatory markers can be useful during the diagnostic workup and management of arthritis, chronic pain, and other inflammatory conditions. C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) are most commonly utilized in clinical practice to quantify the presence of inflammation.

Fecal calprotectin and lactoferrin are non-specific intestinal inflammatory proteins associated with IBD and other inflammatory gut conditions. If you are ordering a comprehensive stool analysis for your patient, they are usually included in, or can be added onto, the test.

An autoimmune panel can measure immune antibodies that will be present if gut dysfunction is stimulating autoimmune responses and triggering joint pain related to autoimmune disease.

Neurotransmitters and Micronutrient Imbalances

Organic acids indicative of intestinal dysbiosis, neurotransmitter imbalances, and micronutrient deficiencies can be assessed through a screening urinary organic acid test (OAT).

Additionally, neurotransmitters, their precursors, and their metabolic byproducts can be measured in urine to assess for imbalances and neuroinflammation.

Extracellular and intracellular micronutrients can be measured to evaluate nutritional status. Results can identify frank nutritional deficiencies and physiologic inactivity of nutrients at the cellular level.

Functional Medicine Treatment for Joint Pain Due to Poor Gut Health

A functional medicine approach to the gut-joint axis is individualized based on diagnosis, lab results, and intake. The following are general guidelines for treatment.


Undoubtedly, dietary modifications can result in the reversal of joint pain and inflammation. There is no one-diet-fits-all approach to treat joint pain, but by utilizing a food-as-medicine approach, we give our bodies what it needs to build a healthy microbiome, regulate the immune system, and reduce systemic inflammation in the body.

Healthcare providers often discuss an anti-inflammatory diet to achieve these goals. General dietary guidelines emphasize consuming nutrient-rich foods containing fiber, essential fatty acids, and phytonutrients to reduce inflammation in the body. Some examples of dietary plans proven to decrease inflammatory markers include the autoimmune protocol (AIP), Mediterranean, and DASH diets. (5, 6)

Increasing foods rich in omega-3 fatty acids, magnesium, B vitamins, vitamin D, and vitamin E have analgesic effects and are associated with decreased reports of joint pain.

Dietary choices also have a profound effect on the microbiome's composition. High consumption of processed and animal-derived foods can encourage dysbiotic microbiome patterns, whereas plant-based diets rich in prebiotic and probiotic foods promote diversity among the commensal bacterial species. The microbiome diet is a three-phase program that can restore gut health by eating microbiome-friendly foods.

Elimination diets personalized to food sensitivity test results may be required to customize anti-inflammatory diets when dietary choices based on anti-inflammatory principles are not enough to reverse joint pain.

The 5-R Protocol

A functional medicine approach to joint pain commonly implements the 5-R Protocol to treat leaky gut syndrome. This protocol removes inflammatory triggers, supports gut healing with natural interventions, and maintains gut health with healthy lifestyle habits. Supplements will often be required through this process and commonly include:

  • Probiotics
  • Butyrate
  • Vitamins and minerals, including vitamin A, vitamin D, and zinc
  • Demulcent herbs, including licorice root, slippery elm, and marshmallow
  • Anti-inflammatories, such as fish oil and curcumin

Increasing Hydration

Dehydration can increase pain sensitivity, exacerbate joint pain, and impair normal bowel function. Water intake recommendations suggest drinking half an ounce of water per pound body weight daily to stay well hydrated.

Vagal Nerve Stimulation

Dysfunction of the vagus nerve can negatively impact the gut-brain axis, promoting poor digestive, immune, and nervous system function. Vagal nerve stimulation (VNS) increases vagal tone to balance neurotransmitter and cytokine production, improving health outcomes in nearly every body system. VNS exercises include mindful meditation, breathwork, yoga, massage, humming, gargling water, and cold exposure.


The gut plays a critical role in regulating the immune system and maintaining a healthy inflammatory balance. Plenty of evidence exists to support the relationship between poor gut health, arthritis, and chronic pain. This is why addressing the gut is one of the primary focuses of functional doctors working with patients suffering from joint pain. Balancing the microbiome, anti-inflammatory diet, and healing intestinal permeability/inflammation are all fundamental components of a functional medicine joint pain treatment plan.

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. Aleksandrova, K., Koelman, L., & Rodrigues, C. E. (2021). Dietary patterns and biomarkers of oxidative stress and inflammation: A systematic review of observational and intervention studies. Redox Biology, 42, 101869.

2. Christ, A., Lauterbach, M. A., & Latz, E. (2019). Western Diet and the Immune System: An Inflammatory Connection. Immunity, 51(5), 794–811.

3. Inflammatory Arthritis and Gut Health. Arthritis Foundation.

4. If you want to boost immunity, look to the gut. (2021, March 19). UCLA Health.,in%20turn%20affect%20immune%20cells.

5. Elma, Ö., Brain, K., & Dong, H. (2022). The Importance of Nutrition as a Lifestyle Factor in Chronic Pain Management: A Narrative Review. Journal of Clinical Medicine, 11(19), 5950.

6. Hart, M.J., Torres, S.J., McNaughton, S.A, et al. Dietary patterns and associations with biomarkers of inflammation in adults: a systematic review of observational studies. Nutr J 20, 24 (2021).

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