# The Oral–Gut–Immune–Nutrition Axis in Rheumatoid Arthritis: Molecular Mechanisms and Therapeutic Implications

## TL;DR

This paper explores how the gut and oral microbiome, along with diet, influence immune responses and inflammation in rheumatoid arthritis, suggesting dietary interventions could help manage the disease.

## Contribution

The paper integrates current evidence on the microbiome–immune–nutrition axis in rheumatoid arthritis, highlighting its therapeutic potential and implications for personalized dietary interventions.

## Key findings

- Microbial alterations in the oral and gut microbiome are linked to immune dysregulation and autoantibody production in rheumatoid arthritis.
- Diet modulates the microbiome-immune-nutrition axis, influencing inflammation and disease outcomes.
- Nutritional and microbiome-targeted interventions may reduce inflammation and comorbidities when combined with standard treatments.

## Abstract

Rheumatoid arthritis is a chronic systemic autoimmune disease that arises from complex interactions among genetic susceptibility, environmental factors, and immune dysregulation. Growing evidence indicates that microorganisms residing in the oral cavity and gastrointestinal tract, together with dietary factors, play a central role in shaping inflammatory and autoimmune responses in rheumatoid arthritis, forming an interconnected microbiome–immune–nutrition axis. Alterations in the composition and function of oral and intestinal microbial communities are associated with disruption of mucosal barrier integrity, activation of innate and adaptive immune pathways, increased differentiation of proinflammatory T lymphocyte subsets, and loss of immune tolerance that promotes autoantibody production. In addition, microbially derived metabolites, particularly short-chain fatty acids, provide a mechanistic link between microbial ecology, immune regulation, and bone metabolism. Diet represents a key upstream modulator of this axis. Dietary patterns rich in anti-inflammatory nutrients support microbial diversity and immunoregulatory metabolite production, whereas diets high in processed foods and saturated fats favor proinflammatory microbial profiles. Accumulating clinical evidence suggests that nutritional strategies and microbiome-targeted dietary interventions may reduce systemic inflammation and disease-related comorbidities when used alongside standard pharmacological treatments. Taken together, the microbiome–immune–nutrition axis represents a modifiable and clinically meaningful target in rheumatoid arthritis, emphasizing the need for interdisciplinary research and well-designed clinical trials to translate these insights into personalized approaches for disease management. The aim of this review is to integrate current mechanistic and clinical evidence on the interactions between the microbiome, immune system, and nutrition in rheumatoid arthritis, with a focus on their pathogenic relevance, therapeutic potential, and implications for personalized, diet-based interventions.