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

doi:10.1016/j.intimp.2020.106270

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 journal › Article › Academic › peer-review

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 language	English
Article number	106270
Number of pages	14
Journal	International Immunopharmacology
Volume	81
DOIs	https://doi.org/10.1016/j.intimp.2020.106270
Publication status	Published - Apr 2020

Keywords

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

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10.1016/j.intimp.2020.106270

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@article{4b184be6ce254a99b4c956807f13c8c1,

title = "Effect of berberine on spleen transcriptome and gut microbiota composition in experimental autoimmune uveitis",

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.",

keywords = "Berberine, Experimental autoimmune uveitis, Transcriptome, Gut microbiota, BACTERIAL DIVERSITY, UVEORETINITIS, TH17, DIFFERENTIATION, INFLAMMATION, DISEASE, CELLS",

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

note = "Funding Information: This study was supported by Research fund for Traditional Chinese Medicine of Chongqing Health and Family Planning Commission ( ZY20141013 ), Natural Science Foundation Major International (Regional) Joint Research Project ( 81720108009 ), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003 ), Chongqing Science & Technology Platform and Base Construction Program ( cstc2014pt-sy10002 ), the Natural Science Foundation Project of Chongqing ( cstc2017shmsA130073 ) and National Natural Science Foundation Key Program ( 81930023 ). Publisher Copyright: {\textcopyright} 2020 Elsevier B.V.",

year = "2020",

month = apr,

doi = "10.1016/j.intimp.2020.106270",

language = "English",

volume = "81",

journal = "International Immunopharmacology",

issn = "1567-5769",

publisher = "Elsevier Science",

}

TY - JOUR

T1 - Effect of berberine on spleen transcriptome and gut microbiota composition in experimental autoimmune uveitis

AU - Du, Ziyu

AU - Wang, Qingfeng

AU - Huang, Xinyue

AU - Yi, Shenglan

AU - Mei, Suyin

AU - Yuan, Gangxiang

AU - Su, Guannan

AU - Cao, Qingfeng

AU - Zhou, Chunjiang

AU - Wang, Yao

AU - Kijlstra, Aize

AU - Yang, Peizeng

N1 - Funding Information: This study was supported by Research fund for Traditional Chinese Medicine of Chongqing Health and Family Planning Commission ( ZY20141013 ), Natural Science Foundation Major International (Regional) Joint Research Project ( 81720108009 ), Chongqing Key Laboratory of Ophthalmology (CSTC, 2008CA5003 ), Chongqing Science & Technology Platform and Base Construction Program ( cstc2014pt-sy10002 ), the Natural Science Foundation Project of Chongqing ( cstc2017shmsA130073 ) and National Natural Science Foundation Key Program ( 81930023 ). Publisher Copyright: © 2020 Elsevier B.V.

PY - 2020/4

Y1 - 2020/4

N2 - 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.

AB - 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.

KW - Berberine

KW - Experimental autoimmune uveitis

KW - Transcriptome

KW - Gut microbiota

KW - BACTERIAL DIVERSITY

KW - UVEORETINITIS

KW - TH17

KW - DIFFERENTIATION

KW - INFLAMMATION

KW - DISEASE

KW - CELLS

U2 - 10.1016/j.intimp.2020.106270

DO - 10.1016/j.intimp.2020.106270

M3 - Article

C2 - 32044663

SN - 1567-5769

VL - 81

JO - International Immunopharmacology

JF - International Immunopharmacology

M1 - 106270

ER -