Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis

He, Jing1,2; Chu, Yanan3; Li, Jing1,2; Meng, Qingren4; Liu, Yudong5; Jin, Jiayang1,2; Wang, Yifan1,2; Wang, Jian3; Huang, Bo1,2; Shi, Lianjie1,2; Shi, Xing6; Tian, Jiayi1,2; Zhufeng, Yunzhi1,2; Feng, Ruiling1,2; Xiao, Wenjing1,2; Gan, Yuzhou1,2; Guo, Jianping1,2; Shao, Changjun3; Su, Yin1,2; Hu, Fanlei1,2; Sun, Xiaolin1,2; Yu, Jun7; Kang, Yu3; Li, Zhanguo1,2,8

2022-02-01

10.1126/sciadv.abm1511

Science Advances   影响因子和分区

2375-2548

The imbalance between pathogenic and beneficial species of the intestinal microbiome and metabolism in rheumatoid arthritis (RA) remains unclarified. Here, using shotgun-based metagenome sequencing for a treatment-naive patient cohort and a "quasi-paired cohort" method, we observed a deficiency of butyrate-producing species and an overwhelming number of butyrate consumers in RA patients. These outcomes mainly occurred in patients with positive ACPA, with a mean AUC of 0.94. This panel was also validated in established RA with an AUC of 0.986 in those with joint deformity. In addition, we showed that butyrate promoted T-regs, while suppressing T-convs and osteoclasts, due to potentiation of the reduction in HDAC expression and down-regulation of proinflammatory cytokine genes. Dietary butyrate supplementation conferred anti-inflammatory benefits in a mouse model by rebalancing T-FH cells and T-regs, as well as reducing antibody production. These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.

SCI ; EI

英语

ESI高被引 ; NI论文

其他

National Natural Science Foundation of China["U1903210",31530020,31970568,82071813,81901648,31671350] ; Beijing Science and Technology Program["Z191100006619114","PKU2020LCXQ018"] ; National Science and Technology Major Project[2018ZX10712001-018-002] ; National Key Research and Development Program of China[2016YFC0903800] ; Chinese Academy of Sciences[QYZDY-SSW-SMC017] ; Macao Science and Technology Fund[0094/2018/A3]

Science & Technology - Other Topics

Multidisciplinary Sciences

WOS:000757383500004

AMER ASSOC ADVANCEMENT SCIENCE

20220711646498

Bone ; Dietary supplements ; Patient treatment

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Food Products:822.3

Web of Science

1.Peking Univ Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
2.Beijing Key Lab Rheumatism Mech & Immune Diag BZ0, Beijing 100044, Peoples R China
3.Chinese Acad Sci, China Natl Ctr Bioinformat, Beijing Inst Genom, CAS Key Lab Genome Sci & Informat, Beijing 100101, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen 518055, Peoples R China
5.Peking Univ Peoples Hosp, Dept Clin Lab, Beijing 100044, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Inst Resp Dis, Dept Resp & Crit Care Med,Shenzhen Peoples Hosp, Shenzhen 518055, Peoples R China
7.Univ Chinese Acad Sci, Beijing 100190, Peoples R China
8.Peking Tsinghua Ctr Life Sci, Beijing 100091, Peoples R China

He, Jing,Chu, Yanan,Li, Jing,et al. Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis[J]. Science Advances,2022,8(6).

He, Jing.,Chu, Yanan.,Li, Jing.,Meng, Qingren.,Liu, Yudong.,...&Li, Zhanguo.(2022).Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis.Science Advances,8(6).

He, Jing,et al."Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis".Science Advances 8.6(2022).