A disease-specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis.
Adult
Aged
Bacterial Load
Bifidobacterium
/ cytology
Case-Control Studies
Cohort Studies
Dysbiosis
/ complications
Feces
/ microbiology
Female
Gastrointestinal Microbiome
Hepatitis, Autoimmune
/ complications
Humans
Liver Cirrhosis, Biliary
/ complications
Male
Middle Aged
RNA, Ribosomal, 16S
/ genetics
Journal
Alimentary pharmacology & therapeutics
ISSN: 1365-2036
Titre abrégé: Aliment Pharmacol Ther
Pays: England
ID NLM: 8707234
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
11
01
2020
revised:
26
01
2020
accepted:
06
04
2020
pubmed:
10
5
2020
medline:
24
11
2020
entrez:
9
5
2020
Statut:
ppublish
Résumé
The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH. To investigate disease-specific microbiome alterations in AIH. The V1-V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81). Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC (P = 0.016), which was partially reversed by azathioprine (P = 0.011). Regarding between-sample diversity, AIH patients separated from HC, PBC and UC individuals (all P = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease-specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH (P < 0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake (P < 0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort. Disease-specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium, which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
Sections du résumé
BACKGROUND
The pathogenesis of autoimmune hepatitis (AIH) is poorly understood and little is known about enteric microbiota in AIH.
AIM
To investigate disease-specific microbiome alterations in AIH.
METHODS
The V1-V2 variable regions of the 16S rRNA gene were sequenced in faecal samples from 347 patients with AIH and controls (AIH n = 72, healthy controls (HC) n = 95, primary biliary cholangitis (PBC) n = 99 and ulcerative colitis (UC) n = 81).
RESULTS
Biodiversity (Shannon entropy) was decreased in AIH patients compared to HC (P = 0.016), which was partially reversed by azathioprine (P = 0.011). Regarding between-sample diversity, AIH patients separated from HC, PBC and UC individuals (all P = 0.001). Compared to HC, decreased relative abundance of anaerobic genera such as Faecalibacterium and an increase of Veillonella and the facultative anaerobic genera Streptococcus and Lactobacillus were detected. Importantly, a disease-specific decline of relative abundance of Bifidobacterium was observed in AIH patients. Lack of Bifidobacterium was associated with failure to achieve remission of AIH (P < 0.001). Of potential therapeutic implication, Bifidobacterium abundance correlated with average protein intake (P < 0.001). Random forests classification between AIH and PBC on the microbiome signature yielded an area under receiver operating characteristic curve (AUC) of 0.787 in the training cohort, and an AUC of 0.849 in an external validation cohort.
CONCLUSION
Disease-specific faecal microbial alterations were identified in patients with AIH. Intestinal dysbiosis in AIH was characterised by a decline of Bifidobacterium, which was associated with increased disease activity. These results point to the contribution of intestinal microbiota to AIH pathogenesis and to novel therapeutic targets.
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1417-1428Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
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