Gut Microbiome Compositional Variance Linked to RA Disease Activity

Minimum clinically important improvement (MCII) status is significantly associated with the variation in gut microbiome community composition in patients with rheumatoid arthritis (RA), according to a study in Genome Medicine.

Investigators analyzed the gut microbiome of patients with RA to identify features that are associated with and are predictive of MCII in disease activity.

The retrospective, observational cohort study included 32 patients with RA (65.6% female). The patients had a mean age of 64.9 years (standard deviation [SD], 11.0) at baseline and a mean disease duration of 8.2 years (SD, 8.2). Stool samples were collected at least 6 to 12 months apart.

Patients’ Clinical Disease Activity Index (CDAI) was measured at both time points to determine MCII achievement. The participants were then grouped into 2 categories—MCII⁺ (those who achieved MCII; n = 12) and MCII⁻ (those who did not achieve MCII; n = 20).

Adjusted model analysis showed that age was the largest determinant of the overall compositional variance in the gut microbiome (R² = 7.7%, P = .001, followed by MCII status (R² = 3.8%, P = .002), and use of conventional synthetic disease-modifying anti-rheumatic drugs (R² = 3.1; P = .008).

A total of 6 microbial taxa were higher in the MCII⁺ group—Negativicutes (class), Selenomonadales (order), Prevotellaceae (family), Coprococcus (genus), Bacteroides sp. 3_1_19 (species), and Bilophila sp. 4_1_ 30 (species). Higher species-level alpha-diversity and beta-diversity were also observed in the MCII⁺ group compared with the MCII⁻ group.

The researchers also found 15 MetaCyc pathways that were differentially abundant between the MCII⁺ and MCII⁻ groups at baseline (P < .05). A total of 6 of these pathways, including multiple ones for tetrahydrofolate biosynthesis and L-methionine biosynthesis, were significantly more common in patients in the MCII⁺ group vs those in the MCII^– group. The other 9 pathways, a majority of which are for L-arginine and L-ornithine biosynthesis and L-rhamnose degradation, were more abundant in patients in the MCII^– group.

Study limitations include the relatively small sample size, which limits the generalization of the findings to a wider range of RA conditions. In addition, the results could be influenced by confounders inherent to the cohort of patients, and stool sample collection and assessment of patients’ disease activity were conducted at only 2 time points.

“Ultimately, we expect our work to be 1 cornerstone for a suite of new, omics data-based clinical tools to aid in early detection, diagnosis, prognosis, and treatment in RA,” the researchers commented. “Looking ahead, possible solutions to treat chronic auto-immune or inflammatory diseases could well involve modifying the gut microbiome to an ecological state primed to enhance clinical outcome.”

Disclosure: One of the study authors declared an affiliation with a pharmaceutical company. Please see the original reference for a full list of authors’ disclosures.

Reference

Gupta VK, Cunningham KY, Hur B, et al. Gut microbial determinants of clinically important improvement in patients with rheumatoid arthritis. Genome Med. 2021;13(1):149. doi:10.1186/s13073-021-00957-0