Case Control Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2021; 13(5): 557-570
Published online May 27, 2021. doi: 10.4254/wjh.v13.i5.557
Gut dysbiosis is associated with poorer long-term prognosis in cirrhosis
Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Aliya Alieva, Ekaterina Kashuh, Ekaterina Tsvetaeva, Elena Poluektova, Elena Shirokova, Konstantin Ivashkin
Roman Maslennikov, Vladimir Ivashkin, Irina Efremova, Aliya Alieva, Ekaterina Kashuh, Ekaterina Tsvetaeva, Elena Poluektova, Elena Shirokova, Konstantin Ivashkin, Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia
Roman Maslennikov, The Interregional Public Organization “Scientific Community for the Promotion of the Clinical Study of the Human Microbiome”, Moscow 119435, Russia
Author contributions: Maslennikov R is the guarantor and finished draft writing; Ivashkin V thought the research idea; Ivashkin V and Maslennikov R made the study design; all authors finished research and data analysis; all authors finished draft editing.
Supported by Biocodex Microbiota Foundation - National Research Grant Russia 2019.
Institutional review board statement: The present study was approved by the Ethics Committee of Sechenov University in accordance with the Declaration of Helsinki (№03-16).
Conflict-of-interest statement: No other conflicts of interest.
Data sharing statement: Dataset available from the corresponding author at maslennikov_r_v@staff.sechenov.ru
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Roman Maslennikov, MD, PhD, Professor, Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Pogodinskaya Street, 1, bld. 1, Moscow 119435, Russia. mmmm00@yandex.ru
Received: January 16, 2021
Peer-review started: January 16, 2021
First decision: February 24, 2021
Revised: February 28, 2021
Accepted: April 22, 2021
Article in press: April 22, 2021
Published online: May 27, 2021
Processing time: 123 Days and 20 Hours
Abstract
BACKGROUND

Gut dysbiosis is common in cirrhosis.

AIM

To study the influence of gut dysbiosis on prognosis in cirrhosis.

METHODS

The case-control study included 48 in-patients with cirrhosis and 21 healthy controls. Stool microbiome was assessed using 16S ribosomal ribonucleic acid gene sequencing. We used modified dysbiosis ratio (MDR): [Bacilli (%) + Proteobacteria (%)]/[Clostridia (%) + Bacteroidetes (%)]. Patients with MDR more the median made up the group with severe dysbiosis, others did the group with non-severe dysbiosis. The follow-up period was 4 years.

RESULTS

The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis (54.2% vs 12.5%; P = 0.001). The presence of severe dysbiosis was independent risk factors for death [hazard ratio = 8.6 × (1.9-38.0); P = 0.005]. The abundance of Enterobacteriaceae (P = 0.002), Proteobacteria (P = 0.002), and Lactobacillaceae (P = 0.025) was increased and the abundance of Firmicutes (P = 0.025) and Clostridia (P = 0.045) was decreased in the deceased patients compared with the survivors. The deceased patients had a higher MDR value than the survivors [0.131 × (0.069-0.234) vs 0.034 × (0.009-0.096); P = 0.004]. If we applied an MDR value of 0.14 as the cutoff point, then it predicted patient death within the next year with a sensitivity of 71.4% and a specificity of 82.9% [area under the curve = 0.767 × (0.559-0.974)]. MDR was higher in patients with cirrhosis than in health controls [0.064 × (0.017-0.131) vs 0.005 × (0.002-0.007); P < 0.001], and in patients with decompensated cirrhosis than in patients with compensated cirrhosis [0.106 × (0.023-0.211) vs 0.033 × (0.012-0.074); P = 0.031]. MDR correlated negatively with prothrombin (r = -0.295; P = 0.042), cholinesterase (r = -0.466; P = 0.014) and serum albumin (r = -0.449; P = 0.001) level and positively with Child–Turcotte–Pugh scale value (r = 0.360; P = 0.012).

CONCLUSION

Gut dysbiosis is associated with a poorer long-term prognosis in cirrhosis.

Keywords: Cirrhosis; Dysbiosis; Gut; ROC-analysis; Microbiota; Microbiome; Gut-liver axis

Core Tip: The mortality rate of patients with severe dysbiosis was significantly higher than that of patients with non-severe dysbiosis. The abundance of Enterobacteriaceae, Proteobacteria, and Lactobacillaceae was increased and the abundance of Firmicutes and Сlostridia was decreased in the deceased patients compared with survivors. The abundance of Bacilli, Enterococcaceae and Lactobacillaceae was higher and the abundance of Clostridia was lower in those who died during the first year of follow-up compared with those who survived this year. The abundance of Enterobacteriaceae and Proteobacteria was higher in those who died in 2nd-4th years of follow-up compared with survivors.