The Gut Microbiome in Autoimmune Liver Diseases Liver Transplant Rejection

Grantee:                       Yael R. Nobel, MD

Institution:                 Columbia University Medical Center

Grant Program:        Autoimmune Liver Diseases Exploratory Research Award

Project Term:             July 2022 - June 2023 (Active)

Area of Focus:            Autoimmune Liver Diseases

Project Description:

Patients with autoimmune liver diseases who require life-saving liver transplant are at risk for acute cellular rejection (ACR), a process through which the patient's immune system can cause dangerous injury to the transplanted liver. By investigating how the gut microbiome - or bacteria that live in the intestine - contribute to immune system activation and ACR after transplant in patients with autoimmune liver diseases, this study will help to identify novel pathways that can ultimately be used to help better predict, prevent, and treat ACR in order to protect patients with autoimmune liver diseases who undergo liver transplant.

Patients with autoimmune liver diseases (AILDs) who develop severe complications may require life-saving liver transplant (LT) but are at risk for dangerous injury to the transplanted liver by the immune system. This includes acute cellular rejection (ACR). In patients with AILDs, the communities of bacteria that live in the intestine - or gut microbiome - are altered. The gut microbiome stimulates the immune system, in part through a group of bacterial products called lipopolysaccharides (LPS).

We hypothesize that the makeup of the gut microbiome, including production of specific types of LPS, contributes to inflammation and ACR after liver transplant in patients with AILDs. In this pilot study, we will compare gut microbiome composition and LPS production in patients with AILDs who developed ACR after liver transplant compared to those who did not develop ACR. This will allow us to identify biological pathways that can be further studied to better predict, prevent, and treat ACR after liver transplant in patients with AILDs. Our findings will also help improve the understanding of liver inflammation more broadly in patients with AILDs.

About the Grantee:

Dr. Yael Nobel is a clinical translational investigator focused on the role of the gut microbiome in liver disease. She is a third-year clinical and research fellow in Gastroenterology and Hepatology at Columbia University Medical Center. She previously completed medical school at the University of Pennsylvania and Internal Medicine Residency and Chief Residency at Columbia University. During fellowship, she is also completing a Master's in Science in Patient-Oriented Research from the Columbia University Mailman School of Public Health.

Inspired by her patients and her mentors in medical school and clinical training, Dr. Nobel developed a passion for both clinical and research work that contribute to the care of patients with liver disease. Dr. Nobel is interested in studying how the gut microbiome contributes to hepatic inflammation in cirrhosis and after liver transplant. The gut microbiome is a potent immune modulator, and could contribute to the development of acute cellular rejection after liver transplant. Supported by this AASLD Foundation award, Dr. Nobel will investigate pathways through which the gut microbiome may contribute to acute cellular rejection in patients with autoimmune liver diseases, who are at increased risk for post-transplant immune-mediated liver injury. In addition to her research, Dr. Nobel will pursue advanced clinical training in Transplant Hepatology as the next step toward her goal of becoming a physician-investigator in Hepatology.

Grantee ORCID Record:

https://orcid.org/0000-0001-5759-3730

More Information*:

NIDDK Liver Transplant Health Information

*Resources are provided for information purposes only and inclusion does not imply AASLD Foundation endorsement or recommendation.

Page last updated January 2023