Abstract
Objectives
This healthy volunteer control-based study was conducted to explore alterations of compositions and function of gut microbiota in Chinese pSS patients.
Method
The high-throughput Illumina Miseq sequencing method, targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene, was used to compare the microbiota communities between 30 pSS patients and 30 age-matched healthy volunteers. The intestinal dysbiosis of pSS patients was evaluated and its correlation with some disease phenotypes was analyzed. Furthermore, we performed the amino acid sequence alignment analysis to illustrate the molecular mimicry patterns of new microbial peptides.
Results
Compared with that in healthy controls, the composition and function of the gut microbiota significantly differed in pSS patients. Certain genera and species, including genera: Escherichia-Shigella, Sardovia, Veillonella, Insteinimonas, and Lactobacillales; species: Escherichia coli, Lactobacillus phage Sal3, Lactobacillus reuteri, Lactobacillus gasseri, Streptococcus lutetiensis, Streptococcus mutans, Scardovia wiggsiae, and Fusobacterrium ulcerans were found to be enriched in the feces of pSS patients, while butyrate-producing bacteria were less abundant in pSS patients. Certain genera (including Lactobacillales) and species (including Lactobacillus gasseri) were associated with disease severity and therapy resistance parameters. Autoantigen epitopes of “WPSALPT, NPARSFG, MNPARSFG, and AFGLAIGT” from aquaporin-5 were aligned perfectly with one enriched microbiota of patients with pSS, namely Escherichia coli.
Conclusions
The composition and function of the gut microbiota significantly differed in pSS patients compared with that in healthy controls. Our study would facilitate the possible research on the role of gut microbiota in the pathogenesis of pSS.
Key Points • The composition and function of the gut microbiota significantly differed in pSS patients compared with that in healthy controls. • Certain genera (including Lactobacillales) and species (including Lactobacillus gasseri) were associated with disease severity and therapy resistance parameters. • The amino acid sequence of Escherichia coli, an enriched species in pSS patients, is similar to those of the pSS-relevant auto-epitopes, such as WPSALPT, NPARSFG, MNPARSFG, and AFGLAIGT, which provides us new clues to explore the exact mechanisms by which Escherichia coli contributes to pSS pathogenesis. |
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Abbreviations
- pSS:
-
Primary Sjögren’s syndrome
- Treg:
-
FoxP3 + regulatory T cells
- SPF:
-
Specific pathogens
- GF:
-
Germ-free
- SCFA:
-
Short-chain fatty acids
- ACR-EULAR:
-
American Congress of Rheumatology–European League Against Rheumatism
- ESSDAI:
-
EULAR Sjögren’s syndrome disease activity index
- IgG:
-
Immunoglobulin G
- IgA:
-
Immunoglobulin A
- IgM:
-
Immunoglobulin M
- Ro/SSA:
-
Ro/Sjögren’s syndrome autoantibody A
- La/SSB:
-
La/Sjögren’s syndrome autoantibody B
- ANA:
-
Antinuclear antibody
- pSS-FC:
-
PSS with a favourable course
- pSS-STR:
-
Most severe and therapy-resistant pSS
- pSS-R:
-
PSS with therapy-resistant
- pSS-NR:
-
Non-therapy resistant pSS
- AGE:
-
Gel electrophoresis
- OTU:
-
Operational taxonomic units
- RDP:
-
Ribosomal Database Project
- PCoA:
-
Principal coordinate analysis
- PICRUSt:
-
Phylogenetic Investigation of Communities by Reconstruction of Unobserved States
- KEGG:
-
Kyoto Encyclopedia of Genes and Genome
- KO:
-
Orthologics
- IEDB:
-
Immune epitope database
- pDCs:
-
Plasmacytoid dendritic cells
- IFN:
-
Interferon
- SLE:
-
Systemic lupus erythematosus
- OmpA:
-
Outer membrane protein
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Acknowledgements
We thank the patients and healthy volunteers who made this study possible and provided their fecal samples. We thank Professor Yudong Liu from Beijing Hospital for the manuscript editing.
Funding
This work was supported by grants from the Natural Science Foundation of China (31140008), CAMS Innovation Fund for Medical Science (2021-12 M-1–050), and Beijing Hospital fund (BJ2014033).
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Clinical analyses and manuscript writing: Yongjing Cheng, Zhe Chen.
Sample and data collection: Fang Wang.
Statistical analyses: Yongjing Cheng, Yunzhi Zhufeng, Jun Xu.
Study design:Fang Wang, Yongjing Cheng.
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Wang, F., Zhufeng, Y., Chen, Z. et al. The composition and function profile of the gut microbiota of patients with primary Sjögren’s syndrome. Clin Rheumatol 42, 1315–1326 (2023). https://doi.org/10.1007/s10067-022-06451-1
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DOI: https://doi.org/10.1007/s10067-022-06451-1