Study on the relationship between intestinal flora and peripheral blood cytokines in patients with rheumatoid arthritis / 中华风湿病学杂志

ABSTRACT

Objective:To detect the characteristics of bacteria in the feces of patients with rheumatoid arthritis (RA) and to further discover the relationship between intestinal flora and the status of peripheral cytokine, which might be able to provide new ideas for clinical treatment.Methods:The bacterial diversity and abundance of 111 RA patients and 100 age-and gender-matched healthy controls (HC) were detected by 16S high-throughput sequencing platform and compared. Based on the 16S rDNA high-throughput sequencing platform, the 16S rDNA V3 region in the participants' fecal specimens were analyzed and compared to screen for different bacterial groups. Alpha diversity was analyzed by the mothur software and the screening for different flora was tested by using Mann-Whitney, and the relationship between intestinal flora and peripheral cytokines were analyzed, too.Results:There was no significant difference in gender ( χ2=0.005, P=0.947) and age ( t=0.728, P=0.467) between the two groups. Patients with RA had a lower chao1 index ( Z=-2.188, P=0.029) and ACE index ( Z=-2.078, P=0.038) of species richness, and the Shannon index ( Z=-2.064, P=0.039) and Simpion index ( Z=-2.064, P=0.039) of diversity index in the feces compared with those of HC. At the genus level, the relative abundance of Bifidobacterium ( Z=-2.388, P=0.017), Lactobacillus ( Z=-2.543, P=0.011), Clostridium sensu stricto ( Z=-3.842, P<0.01), Blautia ( Z=-2.064, P=0.039) , Clostridium Ⅺ ( Z=-2.682, P<0.01), Turicibacter ( Z=-2.437, P=0.015), Phascolarctobacterium ( Z=-3.524, P<0.01), Megasphaera ( Z=-2.87, P<0.01), Veillonella ( Z=-2.472, P=0.013), Citrobacter ( Z=-3.263, P<0.01) and Escherichia/Shigella ( Z=-4.265, P<0.01) in RA were significantly higher than those of HC ( P<0.05), Butyricimonas ( Z=-3.071, P=0.002), Odorbacter ( Z=-2.257, P=0.024), Blautia ( Z=-2.064, P=0.039), Clostridium_ⅩⅣb ( Z=-2.901, P<0.01), Lachnospiracea_incertae sedis ( Z=-2.159, P=0.031), Acetivibrio ( Z=-2.995, P<0.01), Butyricicoccus ( Z=-2.162, P=0.031) and Gemmiger ( Z=-2.949, P<0.01) relative abundance were significantly decreased in RA patients ( P<0.05). LEfSe analysis showed γ-proteobacteria and Lachnospiraceaehad the most significant difference between the two groups. Further, patients with high inflammatory cytokines such as IL-17 and TNF-α hada higher relative abundance of Prevotella. Conclusion:The diversity and abundance of intestinal flora in RA patients are significantly different from those of healthy population, which is closely related to the levels of inflammatory cytokines, suggesting imbalance of intestinal flora might be involved in the occurrence and development of RA.