New Information About the Gut-Joint Axis

The bidirectional communication between the gut microbiome and other key body systems has been well documented. 

“We know about the intricate relationship of the gut to the brain, lung, liver, and skin, so it's not surprising that research is expanding about the gut-joint axis,” said probiotic expert and best-selling author Ross Pelton, RPh, CCN. 

The recognition of the gut-joint axis, however, is relatively new as research continues to grow. A recently published narrative review in the journal Current Rheumatology Reports further illuminates the connection between the gut and joint pain as it relates to the initiation and progression of osteoarthritis (OA).

Mechanistic Considerations

While much still needs to be understood about the molecular pathways involved with the complex interaction between the gut and joints, loss of intestinal integrity seems to play an important role. The authors of the recent review explain that leaky gut syndrome promotes the release of bacterial endotoxins and metabolites such as lipopolysaccharides (LPS) into systemic circulation, leading to increased joint pain. Gut dysbiosis increases the production of zonulin, the protein that contributes to intestinal permeability.

The ensuing chronic systemic inflammation attacks synovial fluid in the joints and increases chondrocyte-intrinsic catabolic responses that can contribute to and magnify joint pain. The authors of the recent narrative paper highlight that there has been growing acceptance of the inflammatory theory regarding the pathogenesis of OA. Research involving the gut microbiome and other arthritic conditions is also increasing.

For example, a recent review published in the journal Frontiers in Cellular and Infection Microbiology described the connection between gut dysbiosis and the onset of rheumatoid arthritis (RA) via multiple pathways, including:

• Alterations in gut barrier function and the microbiome microenvironment
• Molecular mimicry
• Dysbiosis influences the activation and differentiation of innate and acquired immune cells
• Crosstalk between gut microbiota-derived metabolites and immune cells

The authors of that paper also point out that the opposite is true. Metabolites derived from the intestinal microbiota can have anti-inflammatory and immunomodulatory effects.

According to a 2022 review published in Frontiers in Immunology, many in vivo and preclinical studies indicate that a compromised gut microbiome can accelerate the onset of arthritis-associated diseases, including RA.

In addition, a 2020 review published in Nature Reviews Rheumatology outlined the link between gut inflammation and joint pain in patients with spondyloarthritis.

Interestingly, a 2019 review published in Rheumatic & Musculoskeletal Diseases describes research showing that the translocation of bacteria from the gut microbiome into human cartilage was different between patients with OA and healthy controls. The authors of that paper suggest that rebalancing the gut microbiome could enhance cartilage healing by creating metabolites with immunosuppressive properties, which is still another mechanism to consider.

From a clinical perspective, these recent mechanistic discoveries open the doors to potential integrative treatment interventions, including diet, lifestyle, probiotics, and possibly fecal microbiota transplant (FMT).

An Integrative Approach

Focusing on an anti-inflammatory diet seems to be a solid first step when creating an integrative joint health protocol. Reducing the consumption of high-fat foods is foundational to anti-inflammatory eating.

"High-fat diets tend to promote joint inflammation in part by creating a microbiome that releases a lot of the endotoxin LPS, which can eventually find its way into the joint spaces," explained clinician and microbiome expert Mark Davis, ND. “Certain prebiotics and probiotics can sometimes reduce the risk of inflammatory joint pathology, as well as reduce the risk of inflammatory weight gain associated with a high-fat diet.”

A 2020 narrative published in Nutrients highlighted the role of physical activity, a healthy diet, and probiotic supplementation in rebalancing microbial dysbiosis in people with OA. A 2017 randomized, double-blind, placebo-controlled trial published in Beneficial Microbes featuring 537 patients with knee OA found significant improvement in the group taking the probiotics compared to placebo. In addition, the probiotic group also had significantly lower high sensitivity C-reactive protein.

Pelton argues, however, that it’s the postbiotic metabolites that the probiotics produce that are the most important. “Many of the postbiotic metabolites produced by probiotics have anti-inflammatory activity,” explained Pelton. “In order to produce these important postbiotic metabolites, probiotic bacteria require dietary fibers and polyphenols found in plant-based food.” 

That's why a plant-based diet is anti-inflammatory. Pelton says that taking a high-quality probiotic featuring bacterial strains that produce anti-inflammatory postbiotic metabolites is key.

According to a 2021 review published in Arthritis Research & Therapy, in addition to probiotics and prebiotics, FMT may also be an effective intervention to rebalance microbial dysbiosis.

"I have successfully used FMT in my clinical practice; however, when I've used it with patients who have severe RA, psoriatic arthritis, or mild to moderate OA, I have not yet seen a clear benefit in those patients,” said Davis who is considered a leading FMT expert. One reason for the lack of efficacy could be that no clear FMT protocols are available for these patients.

"I tried FMT for patients with autism spectrum disorder before FDA guidelines prohibited it, and I didn't see a response, but years later, clinical trials revealed that FMT can benefit these patients when used in a different manner than I had employed," explained Davis. “Since joint pathologies respond to other microbiome interventions, they may respond to FMT in the right context as well.” Davis agrees that more research in this area is needed.

More Questions Than Answers?

Research increasingly shows that chronic low-grade systemic inflammation can worsen joint conditions; however, some information regarding exact mechanisms is still speculative and requires more research.

“I’m looking forward to the next decade as we will likely learn more about the gut microbiome and how the presence or absence of certain microbes and combinations of microbes influence joint inflammation and repair,” concluded Davis. “Like so many aspects of microbiome research, we don’t know exactly which parts of the microbiome are associated with inflammation and repair.”

Hopefully, research on the horizon will further clarify how to positively influence the gut-joint axis. Until such time, integrative practitioners will continue to utilize the many tools available to remodel the gut, heal dysbiosis, and hopefully relieve joint pain in the process.