human microbiota and liver transplant

Conditions: Intestinal Microbiota; Complication of Transplanted Liver; Acute Rejection of Liver Transplant; Infection

Summary: the microbiota represents the collections of microbial communities that colonize a host. in health, the microbiota protects against pathogens and maturation of the immune system. in return, the immune system determines the composition of the microbiota. altered microbial composition (dysbiosis) has been correlated with a number of diseases in humans. the real role of the microbiota in transplant recipients is still unknown even though we suspect that it may be affected directly or indirectly by immunosuppressive drugs and antimicrobial prophylaxis taken by transplant patients, as well as by inflammatory process secondary to ischemia/reperfusion injury. a number of studies have investigated the impact of liver transplantation on the intestinal microbiota. in a recent analysis of stool flora (microb ecol 2013; 65: 781-791) in 12 liver transplant recipients, changes in the microbiota were correlated to post-transplant infections. the authors suggested that the shift to pathogenic strains of bacteria due to the use of prophylactic antibiotics may be contributing to post-transplant complications. in a larger study, wu et al (hepatobiliary pancreat dis int 2012; 11: 40-50) demonstrated marked changes in the gut microbiota post-transplantation with an increase in enterobacteriaceae and enterococcus, and reduction in eubacteria, bifidobacterium and lactobacillus species. these changes, however, resolved over time such that by 6 months, at times when bacterial prophylaxis ends and immunosuppression is reduced. a better characterization of the impact of post-transplant therapy on the human microbiota has the potential to improve our understanding of the infection process and translate into development of new therapeutic strategies. the main goal of this study is to characterize intestinal microbiota and confirm the same bacterial dna in peripheral blood and portal lymph nodes in patients affected with end-stage chronic liver disease, and to analyze its evolution from the moment of inclusion in waiting list throughout the first year after liver transplantation. for each patient, a healthy control with a similar age (± 10 years) will be selected from the same family setting, in whom just one sample will be obtained during the enrollment phase. the second goal is to analyze the potential associations between microbiota flora and transplant outcomes during the same period.


Eligibility criteria:
inclusion criteria: * first liver transplant * patients aged 18-70 years * able to consent and agree in participate in the current study for one year exclusion criteria: * multiorgan transplantation and/or liver transplant from cardiac arrest donor and/or with abo incompatibility. * uncontrolled concomitant infections (including hiv seropositivity) and/or diarrhoea, vomiting or active gastric ulcer. * fulminant hepatic insufficiency as first indication for liver transplant * hemodynamic instability prior to liver transplant. * recipient presenting present or previous neoplasia, except for non-metastatic basal of squamous cutaneous carcinoma or localized hepatocarcinoma with diameter \<5cm or \<3known lesions with diameter \<3cm. * significant comorbidity * breastfeeding or female patients at fertile age without negative pregnancy test and accepting the use of reliable fertility control method * any pretransplant antibiotherapy (oral or endovenous) or enrolled in any clinical assay

Keywords: intestinal microbiota liver transplant acute rejection infection