Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy

Ruqi Tang, Yiran Wei, Yanmei Li, Weihua Chen, Haoyan Chen, Qixia Wang, Fan Yang, Qi Miao, Xiao Xiao, Haiyan Zhang, Min Lian, Xiang Jiang, Jun Zhang, Qin Cao, Zhuping Fan, Maoying Wu, Dekai Qiu, Jing Yuan Fang, Aftab Ansari, M. Eric GershwinXiong Ma

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Objective A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. Design We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae. Conclusions This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

Original languageEnglish (US)
Pages (from-to)534-571
Number of pages38
JournalGut
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2018

Fingerprint

Ursodeoxycholic Acid
Cholangitis
Therapeutics
Dysbiosis
16S Ribosomal RNA
RNA Sequence Analysis
Microbiota
Enterobacteriaceae
rRNA Genes
Area Under Curve
Cross-Sectional Studies
Biomarkers
Epithelial Cells
Gastrointestinal Microbiome
Prospective Studies
Bacteria

Keywords

  • Intestinal Bacteria
  • Primary Biliary Cirrhosis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. / Tang, Ruqi; Wei, Yiran; Li, Yanmei; Chen, Weihua; Chen, Haoyan; Wang, Qixia; Yang, Fan; Miao, Qi; Xiao, Xiao; Zhang, Haiyan; Lian, Min; Jiang, Xiang; Zhang, Jun; Cao, Qin; Fan, Zhuping; Wu, Maoying; Qiu, Dekai; Fang, Jing Yuan; Ansari, Aftab; Gershwin, M. Eric; Ma, Xiong.

In: Gut, Vol. 67, No. 3, 01.03.2018, p. 534-571.

Research output: Contribution to journalArticle

Tang, R, Wei, Y, Li, Y, Chen, W, Chen, H, Wang, Q, Yang, F, Miao, Q, Xiao, X, Zhang, H, Lian, M, Jiang, X, Zhang, J, Cao, Q, Fan, Z, Wu, M, Qiu, D, Fang, JY, Ansari, A, Gershwin, ME & Ma, X 2018, 'Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy', Gut, vol. 67, no. 3, pp. 534-571. https://doi.org/10.1136/gutjnl-2016-313332
Tang, Ruqi ; Wei, Yiran ; Li, Yanmei ; Chen, Weihua ; Chen, Haoyan ; Wang, Qixia ; Yang, Fan ; Miao, Qi ; Xiao, Xiao ; Zhang, Haiyan ; Lian, Min ; Jiang, Xiang ; Zhang, Jun ; Cao, Qin ; Fan, Zhuping ; Wu, Maoying ; Qiu, Dekai ; Fang, Jing Yuan ; Ansari, Aftab ; Gershwin, M. Eric ; Ma, Xiong. / Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy. In: Gut. 2018 ; Vol. 67, No. 3. pp. 534-571.
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T1 - Gut microbial profile is altered in primary biliary cholangitis and partially restored after UDCA therapy

AU - Tang, Ruqi

AU - Wei, Yiran

AU - Li, Yanmei

AU - Chen, Weihua

AU - Chen, Haoyan

AU - Wang, Qixia

AU - Yang, Fan

AU - Miao, Qi

AU - Xiao, Xiao

AU - Zhang, Haiyan

AU - Lian, Min

AU - Jiang, Xiang

AU - Zhang, Jun

AU - Cao, Qin

AU - Fan, Zhuping

AU - Wu, Maoying

AU - Qiu, Dekai

AU - Fang, Jing Yuan

AU - Ansari, Aftab

AU - Gershwin, M. Eric

AU - Ma, Xiong

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Objective A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. Design We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae. Conclusions This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

AB - Objective A close relationship between gut microbiota and some chronic liver disorders has recently been described. Herein, we systematically performed a comparative analysis of the gut microbiome in primary biliary cholangitis (PBC) and healthy controls. Design We first conducted a cross-sectional study of 60 ursodeoxycholic acid (UDCA) treatment-naïve patients with PBC and 80 matched healthy controls. Second, an independent cohort composed of 19 treatment-naïve patients and 34 controls was used to validate the results. Finally, a prospective study was performed in a subgroup of 37 patients with PBC who underwent analysis before and after 6 months of UDCA treatment. Faecal samples were collected, and microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results A significant reduction of within-individual microbial diversity was noted in PBC (p=0.03). A signature defined by decreased abundance of four genera and increased abundance of eight genera strongly correlated with PBC (area under curve=0.86, 0.84 in exploration and validation data, respectively). Notably, the abundance of six PBC-associated genera was reversed after 6 months of UDCA treatment. In particular, Faecalibacterium, enriched in controls, was further decreased in gp210-positive than gp210-negative patients (p=0.002). Of interest was the finding that the increased capacity for the inferred pathway, bacterial invasion of epithelial cells in PBC, highly correlated with the abundance of bacteria belonging to Enterobacteriaceae. Conclusions This study presents a comprehensive landscape of gut microbiota in PBC. Dysbiosis was found in the gut microbiome in PBC and partially relieved by UDCA. Our study suggests that gut microbiota is a potential therapeutic target and diagnostic biomarker for PBC.

KW - Intestinal Bacteria

KW - Primary Biliary Cirrhosis

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