Abstract
Dysbiosis of gut microbiota and metabolome is a frequently encountered condition in liver cirrhosis (LC) patients. The severity of liver dysfunction was found to be correlated with the degree of microbial dysbiosis. Several clinical studies have indicated liver function improvement after therapeutic splenectomy for LC-induced hypersplenism. We sought to determine whether such post-splenectomy outcome is pertinent to modulation of the abnormal gut microenvironment in LC patients. A cross-sectional study including 12 LC patients and 16 healthy volunteers was first conducted, then a before–after study in the cohort of patients was carried out before and 6 months after splenectomy. Fecal samples were collected in hospital. Temporal bacterial (n = 40) and metabolomics (n = 30) profiling was performed using 16s rRNA gene sequencing and ultra performance liquid chromatography/mass spectrometer (UPLC/MS), respectively. Our results revealed that microbial composition in patients was clearly different from that in healthy controls (HCs), evidenced by considerable taxonomic variation. Along with improved liver function (Child–Pugh score), the patients also displayed similar gut microbiota profile and predicted metagenome function to that of HCs after splenectomy. Enterobacteriaceae and Streptococcaceae, two LC-enriched families showing positive relation with Child–Pugh score, exhibited significantly decreased abundance after splenectomy. At the genus level, 11 genera were differentially abundant between patients and HCs, but 9 genera of them restituted to normal levels by certain degree after splenectomy. PICRUSt analysis showed that the relative abundance of 17 KEGG pathways was partially restored after splenectomy. Four of them were amino acid-related pathways: lysine degradation, tryptophan degradation, amino acid metabolism, and protein digestion and absorption. These findings were supported by metabonomics results which showed that relative abundance of amino acid and corresponding catabolites changed toward normal. In addition to the variations in the relative abundances of bacteria and metabolites, the correlation between them also altered in patients after splenectomy. Dysbiosis in gut microbiome and related metabolism of LC patients was partially corrected after splenectomy. Whether the improved gut microenvironment could prevent LC-related complications and delay the progress of LC is a propitious objective for future study. Trial registration: ChiCTR-OOB-15007409. Registered November 15, 2015.
Highlights
Liver cirrhosis is an advanced liver disease resulting from acute or chronic liver injury, including alcohol abuse, obesity, and hepatitis virus infection
There were three study groups, a cross-sectional study was conducted to see if there was any alternation in gut microbiota and metabonomics in liver cirrhosis (LC) patients with portal hypertension compared with matched healthy controls (HCs)
LC patients exhibited marked impairments in liver function and blood counts compared to HC subjects, and such deleterious alterations were ameliorated after splenectomy
Summary
Liver cirrhosis is an advanced liver disease resulting from acute or chronic liver injury, including alcohol abuse, obesity, and hepatitis virus infection. Liver dysfunction has many effects on the gut, including impaired motility (Chang et al, 1998), reduced bile flow, and altered secretion of immunoglobulin A and anti-microbial molecules (Lu et al, 2011). All of these effects could lead to dysbiosis in the microbiota (Zeuzem, 2000). The gut microbiota that go through dysbiosis play an important role in the development of LC-related complications, including bacterial infections, the hyperdynamic circulatory state, and hepatic encephalopathy (Garcia-Tsao and Wiest, 2004; Riordan and Williams, 2010)
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