The intestinal microbiota and its relationship with colonization and infection by multidrug-resistant bacteria after liver transplantation

• Grant number: 19/04627-4
• Support Opportunities: Scholarships abroad - Research
• Start date: September 02, 2019
• End date: September 01, 2020
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alice Tung Wan Song
• Grantee: Alice Tung Wan Song
• Host Investigator: Anne-Catrin Uhlemann
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: Columbia University in the City of New York, United States

Abstract

Among solid organ transplant individuals, liver recipients are especially vulnerable to colonization and infection by multidrug-resistant bacteria. As a consequence, there are high levels of morbidity and mortality, and a negative impact on post-transplant survival. The knowledge of the risk factors for the development of infections caused by these agents is of extreme importance, in order to investigate alternative prevention strategies, such as probiotic use and fecal transplant. The main objective of this project is to compare the dynamics of the intestinal microbiota between liver transplant recipients who do and do not acquire an MDR bacteria colonization in up to 60 days after transplant. Secondary objectives include: to compare the dynamics of the intestinal microbiota between liver transplant recipients who do and do not acquire an MDR bacteria infection, and between those who survive and those who do not, up to 60 days after transplant; and to analyze the relationship between the intestinal and liver microbiota of the donor and the occurrence of colonization and infection by MDR bacteria after liver transplant. Patients: 100 consecutive patients undergoing liver transplant at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Methods: Characterization of the intestinal and graft microbiota of the donor, explant microbiota, and intestinal microbiota of the receptor (pretransplant, explant and up to 7 more feces samples until 60 days after transplant). After DNA extraction, the hypervariable V3-V4 region of the gene 16S bacterial rRNA will be amplified. The 16S libraries will be sequenced in Illumina MiSeq. Demographical and clinical data from donors and receptors will be prospectively collected, including those related to the risk factors for MDR colonization and infection, as well as results from routine rectal surveillance swabs for carbapenem-resistant Enterobacteriaceae, carbapenem-resistant Acinetobacter sp, and vancomycin-resistant Enterococci. Statistical analysis: the main outcome is acquired colonization by MDR bacteria after transplant and, secondarily, infection by MDR bacteria and death. Univariate and multivariate analysis will be performed for the outcomes. For survival analysis, Kaplan-Meier curves will be constructed, and Cox regression for multivariate analysis. Paired and non-paired t tests will be used to identify significant differences in biodiversity and abundance of microbial lineage between all patients and in different samples from the same patient. P values below 0.05 will be considered significant. Statistical analyses will be performed using SAS and R softwares.