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

doi:10.4254/wjh.v13.i5.557

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

World J Hepatol. 2021 May 27;13(5):557-570. doi: 10.4254/wjh.v13.i5.557.

Authors

Roman Maslennikov¹, Vladimir Ivashkin¹, Irina Efremova¹, Aliya Alieva¹, Ekaterina Kashuh¹, Ekaterina Tsvetaeva¹, Elena Poluektova¹, Elena Shirokova¹, Konstantin Ivashkin¹

Affiliation

¹ Department of Internal Medicine, Gastroenterology and Hepatology, Sechenov University, Moscow 119435, Russia.

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; Gut-liver axis; Microbiome; Microbiota; ROC-analysis.