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Abstract Number: 0514

Efficacy, Safety and Mechanism of Butyrate in the Treatment of Rheumatoid Arthritis (RA)

Jing He1, Naidi Wang2, Yuhui Li3, Ruoyi Wang2, Xiao Tan2, Runzhi Zhufeng2, Yipeng Han2, Hao Li2, Yuebo Jin2 and Zhanguo Li4, 1Rheumatology, Beijing, China, 2Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China, 3Peking University, BeiJing, China, 4People’s Hospital Peking University Health Sciences Centre, Beijing, China

Meeting: ACR Convergence 2024

Keywords: microbiome, rheumatoid arthritis, Treg cells

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Session Information

Date: Saturday, November 16, 2024

Title: RA – Treatment Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: This study aims to investigate the safety and efficacy of butyrate capsules in treating patients with rheumatoid arthritis (RA) and elucidate the underlying mechanisms.

Methods: A 12-week single-arm trial with 30 RA patients collected clinical data, blood for flow cytometry and RNA sequencing, serum for ELISA to measure intestinal injury markers, and fecal samples for metagenomic sequencing and metabolite analysis using gas chromatography-mass spectrometry.

Results: No adverse events were observed in RA patients after taking butyrate. Compared to pre-treatment, the CRP and ESR levels significantly decreased after 12 weeks of treatment  [0.25(0.25,1.37) vs 0.6(0.25,6.28) mg/L, P=0.040; 11(7,14) vs 17(7,23) mm/h], P=0.026). The CDAI, SDAI, DAS28-ESR and DAS28-CRP of RA patients also decreased significantly (P=0.002, P<0.001, P=0.027, P=0.023, respectively). LBP levels in RA patients decreased significantly (2.53±2.17 vs 6.01±2.10μg/mL, P<0.001), and sCD14 levels also showed a downward trend (P=0.414). Compared to pre-treatment (4.03±1.57%), Treg cells(5.28±1.52%)increased significantly (P<0.001), as did in Treg/Tfh (P=0.001). The proportion of CD19+B cells and antibody-secreting cells decreased significantly after treatment [5.96±2.39 vs 9.13±3.72%, P<0.001; 1.59(0.95,2.78) vs 2.54(1.21,4.63)%, P=0.031]. Significant differences in the mRNA profile of CD4+ T cells were observed before and after butyrate treatment, with NR4A3 and APOE (two Treg-related genes) significantly up-regulated (P=0.008; P=0.029). Post-treatment, alpha diversity of intestinal flora tended to increase (P >0.05). Serum butyrate levels (21.84±7.48 μM) were significantly higher after treatment compared to pre-treatment (15.38±4.68 μM, P=0.003), while fecal butyrate levels did not change significantly (P=0.631).

Conclusion: Butyrate capsules are safe and effective for RA, reducing disease activity and inflammation, and suggesting new dietary or microbial therapy options.

Supporting image 1

Supporting image 2

Figure 1. Changes of disease activity and immune cell subsets in RA patients after butyrate capsule treatment.
(a-b) Changes of inflammatory indexes (CRP, ESR, respectively) after butyrate capsule treatment. (a): CRP; (b): ESR. (c-f) Changes of disease activity (CDAI, SDAI, DAS28-ESR, DAS28-CRP, respectively) after butyrate capsule treatment. (c):CDAI; (d):SDAI; (e):DAS28-ESR; (f): DAS28-CRP. (g-h) Changes of the percentage of Treg cells after butyrate capsule treatment. (i) Changes of the ratio of Treg cells to Tfh after butyrate capsule treatment. (j-k) Changes of B cell subsets (CD19+B, ASC, respectively) after butyrate capsule treatment. (j): CD19+B; (k):ASC.
ASC: antibody-secreting plasma cell; CDAI: clinical disease activity index; CRP: C-reactive protein DAS28: disease activity score in 28 joints; ESR: erythrocyte sedimentation rate; SDAI: simplified disease activity index; Treg: regular T cell; Tfh: follicular helper T cell.

Supporting image 3

Figure2. Effect of mRNA and short chain fatty acid levels in patients with RA after butyrate treatment.
(a): Changes of mRNA profile of CD4+T cells after butyrate treatment. (b): Differential genes before and after treatment. Red represents up-regulated genes and green represents down-regulated genes.(c): Differential gene expression in different samples. (d): Changes in expression of differential genes associated with Treg (NR4A3, PLAU and APOE, respectively) before and after treatment. (e): Changes of short-chain fatty acids level in serum and fecal samples after treatment. APOE: apolipoprotein E; NR4A3: nuclear receptor subfamily 4 group A member 3; PLAU: plasminogen activator urokinase.


Disclosures: J. He: None; N. Wang: None; Y. Li: None; R. Wang: None; X. Tan: None; R. Zhufeng: None; Y. Han: None; H. Li: None; Y. Jin: None; Z. Li: None.

To cite this abstract in AMA style:

He J, Wang N, Li Y, Wang R, Tan X, Zhufeng R, Han Y, Li H, Jin Y, Li Z. Efficacy, Safety and Mechanism of Butyrate in the Treatment of Rheumatoid Arthritis (RA) [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/efficacy-safety-and-mechanism-of-butyrate-in-the-treatment-of-rheumatoid-arthritis-ra/. Accessed .
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