Microbiota Study in Liver Transplanted Patients

Many studies describe the relationship between microbiota alteration and the occurrence of metabolic, alcoholic or inflammatory liver diseases. Nevertheless, the modifications of microbiota during liver transplantation (LT) as well as its implication are poorly studied. Similarly, only the intestinal microbiota is studied in this context, and no data are available on the biliary microbiota, even if it is known that bile microbiota can interfere with hepatobiliary diseases.

This study proposes a clinical and biological in-depth follow-up with multiple sampling of liver transplanted patients to study biliary and intestinal microbiota alterations along LT, as well as bile acids metabolism in corresponding fluids.

Indeed, in recipient samples as saliva, blood, urine, and feces can be taken before LT, and surgeons can easily perform bile sampling during LT. In donors all samples can be taken during liver removal. This offers the opportunity to have a microbiotic landscape of individuals without liver disease (donor), and patients suffering from a chronic liver disease or a liver cancer before and after transplantation.

Also, in Grenoble University hospital, in case of biliary anastomotic incongruence, a biliary stent is placed during LT in 60% of recipients. This stent is removed by endoscopic retrograde cholangiopancreatography (ERCP) within 6 months after LT, offering a second opportunity to obtain bile samples in transplanted patients, after the early post-LT period. Patients who do not require a biliary stent will also be included for the study of secondary objectives, as intestinal microbiota is very poorly characterized in liver transplanted patients too. A portion of the patients without biliary stent, may also develop an anastomotic biliary stricture requiring an ERCP. If this ERCP is realized within the follow-up period of the study, the patient will also be included in the primary objective of the study.

These multiple and sequential samples will allow a complete analysis of microbiota changes in LT patients and aim to answer to 3 questions:

1. What are the modifications of intestinal and biliary microbiomes during LT? 2. What is the influence of bile acids' composition on intestinal and biliary microbiota? 3. What are the relationships between microbiome alterations and the emergence of LT complications?