Intestinal Permeability In Subjects With Rheumatoid Arthritis: A Critical Therapeutic Priority

Rheumatoid arthritis is increasingly being recognized as the synovial manifestation of a group of systemic autoinflammatory conditions known as immune-mediated inflammatory diseases. While each of these conditions displays unique diagnostic signs and symptoms based on the tissue targeted by inflammation, most immune-mediated inflammatory diseases share common features, including their immune-signaling pathways. Owing to these similarities, great advances have emerged in the past few decades using therapies designed to block downstream inflammatory mediators (eg, cytokine-blocking biologics, Janus Kinase (JAK) inhibitors). Unfortunately, fewer advances have been made in therapies that have the potential to target the upstream antecedents and triggers of these complex inflammatory diseases, such as the immunologic chain of events triggered by intestinal hyperpermeability (ie, leaky gut) or gastrointestinal dysbiosis (ie, alterations in the gut microbiota). In the past few decades, intestinal hyperpermeability has emerged as an important antecedent for a wide range of chronic immunological and metabolic conditions, including celiac disease, obesity, cardiovascular disease, and a number of immune-mediated inflammatory diseases such as inflammatory bowel disease, psoriasis, and rheumatoid arthritis. In this narrative review, we discuss the growing awareness that biomarkers of intestinal permeability are frequently associated with non-gastrointestinal immune-mediated inflammatory diseases, particularly those associated with the gut-joint axis, such as rheumatoid arthritis. We suggest that measures of intestinal permeability, along with lifestyle and nutrient interventions that target gut-barrier function, may be important adjunctive clinical tools to help patients with rheumatoid arthritis achieve and maintain remission.