Altered Microbiome in Patients With Cirrhosis and Complications

Abstract

In patients with cirrhosis, the gut microbiome are affected by multiple gut and systemic alterations. These changes lead to dysbiosis in the microbiota of different parts of the body, resulting in inflammation. The constant immune stimulation resulting in part from dysbiosis is associated with morbidity in patients with cirrhosis. Dysbiosis as a dynamic event worsens with decompensation such as with hepatic encephalopathy, infections or acute-on-chronic liver failure (ACLF). These microbial patterns could be applied as diagnostic and prognostic measures in cirrhosis in the outpatient and inpatient setting. Current therapies for cirrhosis have differing impacts on gut microbial composition and functionality. Dietary modifications and the oral cavity have emerged as newer targetable factors to modulate the microbiome, which could affect inflammation and, potentially improve outcomes. Additionally, fecal microbial transplant is being increasingly studied to provide compositional and functional modulation of the microbiome. Ultimately, a combination of targeted therapies may be needed to provide an optimal gut milieu to improve outcomes in cirrhosis.

Keywords: Dysbiosis; Fecal Microbial Transplant; Hepatic Encephalopathy; Oral; Outcomes.

Figure 1:

Pathway for specimen processing and bioinformatics analysis for 16s and metagenomic analysis for microbiota

Figure 2:

Multiple levels of immune dysfunction in cirrhosis, which are complicit in allowing alteration of microbiota in the gut and elsewhere. GALT: Gastrointestinal associated lymphoid tissue, SIBO: small intestinal bacterial overgrowth, BA: bile acids, RES: reticulo-endothelial system

Figure 3:

Schematic of changes of key features with progression from healthy to acute-on-chronic liver failure and resolution after liver transplant. ACLF: acute on chronic liver failure, PPI: proton pump inhibitors