Citation

Bajaj JS, Kakiyama G, Zhao D, Takei H, Fagan A, Hylemon P, Zhou H, Pandak WM, Nittono H, Fiehn O, Salzman N, Holtz M, Simpson P, Gavis EA, Heuman DM, Liu R, Kang DJ, Sikaroodi M, Gillevet PM. Alcohol Clin. Exp. Res. 2017; 41(11): 1857-1865.

Affiliation

George Mason University, Manassas, Virginia, USA.

Copyright

(Copyright © 2017, John Wiley and Sons)

DOI

10.1111/acer.13498

PMID

28925102

Abstract

BACKGROUND: Cirrhosis and alcohol can independently affect the gut-liver axis with systemic inflammation. However their concurrent impact in humans is unclear.

AIM: Determine the effect of continued alcohol misuse on the gut-liver axis in cirrhotic patients.

METHODS: Age and MELD-balanced cirrhotic patients who were currently drinking (Alc) or abstinent (NAlc), and healthy controls underwent serum and stool collection. A subset underwent upper endoscopy and colonoscopy for biopsies and duodenal fluid collection. The groups were compared regarding (1) inflammation/intestinal barrier: systemic TNF levels, intestinal inflammatory cytokine (duodenum, ileum, sigmoid) and ileal anti-microbial peptide expression (2) microbiota composition: 16SrRNA sequencing of duodenal, ileal, colonic mucosal and fecal microbiota (3) microbial functionality: duodenal fluid and fecal BA profile (conjugation and dehydroxylation status), intestinal BA transporter (ASBT, FXR, FGF-19, SHP) expression and stool metabolomics using GC/MS.

RESULTS: Alc patients demonstrated a significant duodenal, ileal and colonic mucosal and fecal dysbiosis, compared to NAlc and controls with lower autochthonous bacterial taxa. BA profile skewed towards a potentially toxic profile (higher secondary and glycine-conjugated BAs) in duodenal fluid and stool in Alc patients. Duodenal fluid demonstrated conjugated secondary BAs only in the Alc group. There was a greater expression of all ileal BA transporters in Alc patients. This group also showed higher endotoxemia, systemic and ileal inflammatory expression and lower amino acid and bioenergetic-associated metabolites, without change in anti-microbial peptide expression.

CONCLUSIONS: Despite cirrhosis, continued alcohol misuse predisposes patients to widespread dysbiosis with alterations in microbial functionality such as a toxic bile acid profile, which can lead to intestinal and systemic inflammation. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Language: en

Keywords

Bile acids; functionality; inflammation; metabolomics; microbiota