Effect of berberine on spleen transcriptome and gut microbiota composition in experimental autoimmune uveitis

Ziyu Du, Qingfeng Wang, Xinyue Huang, Shenglan Yi, Suyin Mei, Gangxiang Yuan, Guannan Su, Qingfeng Cao, Chunjiang Zhou, Yao Wang, Aize Kijlstra, Peizeng Yang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Web of Science)

Abstract

Background: Berberine (BBR) was reported to have immunoregulatory and anti-inflammatory properties. In this study, we investigated whether BBR could exert its effects on the development of experimental autoimmune uveitis (EAU), and if so, what was the underlying mechanism?

Methods: EAU was induced in B1 OR.III mice by immunization with IRBP 161-180, followed by 100 mg/kg/d BBR intragastric administration. Disease severity was assessed by evaluation of clinical and histopathological scores. Blood-retinal barrier (BRB) breakdown was tested by Evans blue. Effector and regulatory T (Treg) cell balance was evaluated by quantitative real-time PCR and flow cytometry. Spleen transcriptome was characterized by RNA sequencing (RNA-seq). Gut microbiota composition was investigated by 16S rRNA analysis.

Results: BBR treatment significantly blocked EAU as shown by the decrease of the clinical and histological scores, as well as the inhibition of BRB breakdown. The frequency of splenic Th1 and Th17 cells was decreased, whereas Treg cells were increased in the BBR-treated group. RNA-seq of the spleen revealed 476 differentially expressed genes (DEGs) between the EAU and EAU-BBR group. GO functional classification, as well as KEGG analysis demonstrated that BBR treatment markedly influences genes belonging to chromatin remodeling and immune-related pathways. Intervention with BBR modified the gut microbiome in EAU mice, increasing the number of bacteria with immunomodulatory capacity. Depletion of gut microbiota affected the efficacy of BBR on EAU. Moreover, the altered bacterial strains showed a significant correlation with the expression of histones.

Conclusions: BBR inhibited IRBP induced EAU, which was associated with a significant change in the spleen transcriptome and intestinal microbial composition.

Original languageEnglish
Article number106270
Number of pages14
JournalInternational Immunopharmacology
Volume81
DOIs
Publication statusPublished - Apr 2020

Keywords

  • Berberine
  • Experimental autoimmune uveitis
  • Transcriptome
  • Gut microbiota
  • BACTERIAL DIVERSITY
  • UVEORETINITIS
  • TH17
  • DIFFERENTIATION
  • INFLAMMATION
  • DISEASE
  • CELLS

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