Multidimensional profile of gut microbiota in a large cohort of stratified rheumatoid arthritis

Abstract

Abstract It is unknown if dysbiosis of microbiota plays a role in the initiation and severity of rheumatoid arthritis (RA). In a comprehensive study of 2297 individuals, including 1,064 RA patients and 1,233 healthy controls, we uncovered an age-related trajectory fluctuation of intestinal microbiota in RA which clearly coincided with the peak age of RA onset. Patients at RA onset exhibited a significant reduction in anti-inflammatory species like Akkermansia muciniphila, Butyrivibrio proteoclasticus, and Rumlnococcus albus. Conversely, pro-inflammatory bacteria Escherchia coli, Parabacteroldes distesonis, and Velllonella parvula were largely enriched. Samples in different clusters show distinct microbial patterns, and associated with treatment response. Specific gut microbiota was closely linked to RA's clinical features and systemic involvements, especially interstitial lung disease (ILD). Our predictive model based on gut microbiota successfully distinguished RA with systemic impairment from those with mainly joint involvements. Additionally, a 6-year follow-up cohort showed that lower disease activity associated with increased abundance of Streptococcu salivarius, Anaerostipehadrus, and lactobacillus fermentum. These findings suggest that gut microbiota may trigger RA initiation, and are associated with aggravated and systemic damages of the disease, and could lead to more personalized and effective treatment strategies.