口腔链球菌失调可能促进关节炎的发生发展 | 热心肠日报

Annals of the Rheumatic Diseases

[IF:16.102]

Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice

类风湿关节炎患者口腔中富集的链球菌属物种产生的肽聚糖-多糖聚合物可诱导小鼠关节炎

10.1136/annrheumdis-2020-219009

01-04, Article

Abstract & Authors:展开

Abstract:收起
Objectives : Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the oral microbiota in a prospective cohort of patients with RA, first-degree relatives (FDR) and healthy controls (HC), then genomically and functionally characterised streptococcal species from each group to understand their potential contribution to RA development.
Methods: After DNA extraction from tongue swabs, targeted 16S rRNA gene sequencing and statistical analysis, we defined a microbial dysbiosis score based on an operational taxonomic unit signature of disease. After selective culture from swabs, we identified streptococci by sequencing. We examined the ability of streptococcal cell walls (SCW) from isolates to induce cytokines from splenocytes and arthritis in ZAP-70-mutant SKG mice.
Results: RA and FDR were more likely to have periodontitis symptoms. An oral microbial dysbiosis score discriminated RA and HC subjects and predicted similarity of FDR to RA. Streptococcaceae were major contributors to the score. We identified 10 out of 15 streptococcal isolates as S. parasalivarius sp. nov., a distinct sister species to S. salivarius. Tumour necrosis factor and interleukin 6 production in vitro differed in response to individual S. parasalivarius isolates, suggesting strain specific effects on innate immunity. Cytokine secretion was associated with the presence of proteins potentially involved in S. parasalivarius SCW synthesis. Systemic administration of SCW from RA and HC-associated S. parasalivarius strains induced similar chronic arthritis.
Conclusions : Dysbiosis-associated periodontal inflammation and barrier dysfunction may permit arthritogenic insoluble pro-inflammatory pathogen-associated molecules, like SCW, to reach synovial tissue.

First Authors:
Rabia Moentadj,Yiwen Wang,Kate Bowerman

Correspondence Authors:
Ranjeny Thomas

All Authors:
Rabia Moentadj,Yiwen Wang,Kate Bowerman,Linda Rehaume,Hendrik Nel,Páraic Ó Cuív,Juliette Stephens,Amalina Baharom,Muralidhara Maradana,Vanessa Lakis,Mark Morrison,Timothy Wells,Philip Hugenholtz,Helen Benham,Kim-Anh Lê Cao,Ranjeny Thomas