Abstract
Emerging evidence suggests that altered intestinal microbiota plays an important role in the pathogenesis of many liver diseases, mainly by promoting inflammation via the “intestinal microbiota-immunity-liver” axis. We aimed to investigate the fecal microbiome of liver recipients with abnormal/normal liver function using 16S rRNA gene sequencing. Fecal samples were collected from 90 liver recipients [42 with abnormal liver function (Group LT_A) and 48 with normal liver function (Group LT_N)] and 61 age- and gender-matched healthy controls (HCs). Fecal microbiomes were analyzed for comparative composition, diversity, and richness of microbial communities. Principal coordinates analysis successfully distinguished the fecal microbiomes of recipients in Group LT_A from healthy subjects, with the significant decrease of fecal microbiome diversity in recipients in Group LT_A. Other than a higher relative abundance of opportunistic pathogens such as Klebsiella and Escherichia/Shigella in all liver recipients, the main difference in gut microbiome composition between liver recipients and HC was the lower relative abundance of beneficial butyrate-producing bacteria in the recipients. Importantly, we established a fecal microbiome index (specific alterations in Staphylococcus and Prevotella) that could be used to distinguish Group LT_A from Group LT_N, with an area under the receiver operating characteristic curve value of 0.801 and sensitivity and specificity values of 0.771 and 0.786, respectively. These findings revealed unique gut microbial characteristics of liver recipients with abnormal and normal liver functions, and identified fecal microbial risk indicators of abnormal liver function in liver recipients.
Highlights
Liver transplantation is a common and effective therapy for endstage liver diseases
Patients were considered for enrollment if they diagnosed with pathologically-diagnosed hepatitis B virus (HBV)-associated hepatocellular carcinoma with the Barcelona Clinic Liver Cancel (BCLC) stage A or B, and the Child -Pugh class A or B who met the Hangzhou criteria and had undergone liver transplantation more than 24 months but less than 48 months prior to the study period
The immunosuppressive therapies prescribed in the 6 months postLT included simulect, mycophenolate mofetil, glucocorticoids, and FK506 tacrolimus; all drugs were used at doses adjusted according to patient situation based on several factors, including their patient status, platelet count, and white blood cell count
Summary
Liver transplantation is a common and effective therapy for endstage liver diseases. As of 2015, more than 1,700 living-donor liver transplantations had been successfully performed at the First Affiliated Hospital, College of Medicine of Zhejiang University, China, with an overall 3 years post-surgery survival rate of more than 70%. The human intestinal tract harbors about 100 trillion microbes They play a role in the development of mucosal and systemic immunity and are involved in host liver disease (Lu et al, 2011; Qin et al, 2014; Chen et al, 2016). Malnutrition, ischemia-reperfusion injury (Ren et al, 2013), and immunosuppression therapy in liver transplant (LT) recipients directly lead to dysbiosis, disrupted intestinal barriers, and alterations in the innate immune response. Immunosuppressors (e.g., FK506 and CsA) were initially reported to impair intestinal permeability in animals (Gabe et al, 1998), clinical studies on the chronic effects of FK506 and CsA on the intestine of liver recipients 2–4 years post-orthotopic LT (Parrilli et al, 2003) showed that these immunosuppressors did not affect intestinal permeability
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