Community-Metabolome Correlations of Gut Microbiota from Child-Turcotte-Pugh of A and B Patients

Abstract

The gut flora are widely involved in the cometabolism with the host and have evident effects on the metabolic phenotype of host. This study performed a metabolome analysis of the intestinal microbiota specific for liver cirrhosis. The study population included patients with Child-Turcotte-Pugh score of A (AP, n = 5) and B (BP, n = 5), and control subjects (NM, n = 3). Metagenomic DNA from fecal microbiota was extracted followed by metagenomic sequencing through Illumina MiSeq high throughput sequencing of 16S rRNA regions. The detection of metabolites from fecal samples was performed using high-performance liquid phase chromatography and gas chromatography coupled with tandem mass spectrometry. Intestinal microbiota community and metabolite analysis both showed separation of cirrhotic patients from control participants, moreover, the microbiota–metabolite correlations changed in cirrhotic patients. Fecal microbiota from cirrhotic patients, with the reduced diversity, contained a decreased abundance of Bacteroidetes and an increased abundance of Firmicutes and Proteobacteria compared with the normal samples. Analysis of metabolome revealed a remarkable change in the metabolic potential of the microbiota in cirrhotic patients, with specific higher concentrations of amine, unsaturated fatty acid, and short-chain fatty acids, and lower concentrations of sugar alcohol and amino acid, suggesting the initial equilibrium of gut microbiota community and co-metabolism with the host were perturbed by cirrhosis. Our study illustrated the relationship between fecal microbiota composition and metabolome in cirrhotic patients, which may improve the clinical prognosis of cirrhosis.

Fecal microbiota and metabolome characteristics in cirrhotic patients accompanied with hepatic encephalopathy

“…Hepatic encephalopathy was regarded as a typical model of gut-liver-brain axis diseases [11]. Gut microbiota had extensive participation in human metabolism [4]. In cirrhotic patients, changes of intestinal microbial community and the metabolic byproducts, local and systemic inflammation, and intestinal barrier dysfunction will drive the development of hepatic encephalopathy [11].…”

“…Gut microbiota is considered as an important endocrine organ, which can be adjusted or self-regulated [1]. Intestinal microbiota has intimate relationship with human disease and health, and has remarkable influence on the metabolic phenotype of host, with extensive participation in the cometabolism with host [3,4].…”

“…Liver has intimate relationship with the gut through physiological structure of gut-liver axis [5]. Previous studies had suggested cirrhosis-specific characteristics of intestinal microbiota community and cometabolome with the host [4,6,7]. Hepatic encephalopathy (HE) was the major complication for cirrhosis, and the liver was functional disordered in CHE patients, directly affecting the intestinal microenvironment, and further affecting gut microbiota community and metabolism.…”

Splenectomy Leads to Amelioration of Altered Gut Microbiota and Metabolome in Liver Cirrhosis Patients

“…Another study showed similar result that Child–Pugh B patients contained a significant reduction of Bacteroidetes and increase in Firmicutes and Proteobacteria compared with the health people. While fecal microbiota component from Child–Pugh A patients had no significant difference from the health people ( Wei et al, 2016 ). These results indicated that normal gut microbiota depend on normal liver function, and improved liver function observed after splenectomy might have helped to restore gut microenvironment.…”

“…Dysbiosis in microbiota can disrupt the metabolic balance in the gastrointestinal tract ( Marcobal et al, 2013 ). Previous studies have reported that LC patients exhibit a distinct metabolic phenotype, such as disordered amino acid metabolism ( Huang et al, 2013 ; Wei et al, 2013 , 2016 ). In turn, the dysbiosis of gut microbiota may contribute to the progress of liver disease ( De Minicis et al, 2014 ; Tilg et al, 2016 ).…”