Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: The Microbiome, Microbial Markers and Liver Disease Study

Jonathan P Jacobs; Tien S Dong; Vatche Agopian; Venu Lagishetty; Vinay Sundaram; Mazen Noureddin; Walid S Ayoub; Francisco Durazo; Jihane Benhammou; Pedram Enayati; David Elashoff; Marc T Goodman; Joseph Pisegna; Shehnaz Hussain

doi:10.1111/hepr.13207

Microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis: The Microbiome, Microbial Markers and Liver Disease Study

Hepatol Res. 2018 Dec;48(13):1108-1117. doi: 10.1111/hepr.13207. Epub 2018 Jul 30.

Authors

Jonathan P Jacobs^{1

2

3}, Tien S Dong³, Vatche Agopian⁴, Venu Lagishetty³, Vinay Sundaram⁵, Mazen Noureddin⁵, Walid S Ayoub⁵, Francisco Durazo^{3

4}, Jihane Benhammou¹, Pedram Enayati⁵, David Elashoff⁶, Marc T Goodman⁷, Joseph Pisegna¹, Shehnaz Hussain^{7

8}

Affiliations

¹ Division of Gastroenterology, Hepatology and Parenteral Nutrition, VA Greater Los Angeles Healthcare System and Department of Medicine and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
² UCLA Microbiome Center, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
³ The Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁴ Departments of Surgery, University of California, Los Angeles, Los Angeles, California, USA.
⁵ Division of Digestive and Liver Diseases, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁶ Department of Biostatistics, Fielding School of Public Health, University of California , Los Angeles, Los Angeles, California, USA.
⁷ Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁸ Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, California, USA.

Abstract

Aim: Cirrhosis is a leading cause of death worldwide, yet there are no well-established risk stratifying tools for lethal complications, including hepatocellular carcinoma (HCC). Patients with liver cirrhosis undergo routine endoscopic surveillance, providing ready access to duodenal aspirate samples that could be a source for identifying novel biomarkers. The aim of this study was to characterize the microbiome and bile acid profiles in duodenal aspirates from patients with liver cirrhosis to assess the feasibility of developing biomarkers for HCC risk stratification.

Methods: Thirty patients with liver cirrhosis were enrolled in the Microbiome, Microbial Markers, and Liver Disease study between May 2015 and March 2017. Detailed clinical and epidemiological data were collected at baseline and at 6-monthly follow-up visits. Duodenal aspirate fluid was collected at baseline for microbial characterization using 16S ribosomal RNA sequencing and bile acid quantification using mass spectroscopy.

Results: Alcohol-related cirrhosis was associated with reductions in the Bacteroidetes phylum, particularly Prevotella (13-fold reduction), and expansion of Staphylococcus (13-fold increase), compared to hepatitis C virus-related cirrhosis. Participants with hepatic encephalopathy (HE) had less microbial diversity compared to patients without HE (P < 0.05), and were characterized by expansion of Mycobacterium (45-fold increase) and Gram-positive cocci including Granulicatella (3.1-fold increase), unclassified Planococcaceae (3.3-fold increase), and unclassified Streptococcaceae (4.5-fold increase). Non-Hispanic White patients had reduced microbial richness (P < 0.01) and diversity (P < 0.05), and increased levels of conjugated ursodeoxycholic acid (glycoursodeoxycholic acid and tauroursodeoxycholic acid, P < 0.05) compared to Hispanic patients.

Conclusion: Microbial profiles of duodenal aspirates differed by cirrhosis etiology, HE, and Hispanic ethnicity.

Keywords: bile acids; cirrhosis; microbiome.

Abstract

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