Gut Microbiome Analysis in Organ Transplant Recipient

NCT ID: NCT06405958

Last Updated: 2024-05-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 200 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2026-12-31

Brief Summary

The microbiome acts as an antigen and can induce signaling through receptors like TLRs and NODs. Microbial metabolites can directly act on gut cells or reach other organs systemically. Studies show that the commensal, non-pathogenic microbiota plays an important role in regulating the immune system in various ways:

• Promoting differentiation of Th17 cells and ILC3 signaling to regulate IL-17A production
• Influencing iNKT cell generation early in life to prevent inflammatory activities
• Facilitating CD4+ T cell differentiation and balancing Th1/Th2 responses
• Inducing regulatory T cells (Tregs) that promote immune homeostasis
• Tregs in Peyer's patches help maintain a microbiome that supports homeostasis

The microbiome influences T cells, B cells and immune homeostasis. This has implications for transplantation, where modulating the microbiome could impact the graft's acceptance by affecting the recipient's immune cells that respond to the transplant.

In summary, it highlights the microbiome's role in immune regulation and the potential for leveraging this interaction therapeutically, including in the context of transplantation.

Detailed Description

The microorganisms coexisting in our bodies are known to be involved in immune functions in various ways. The microbiome basically acts as an antigen in the immune system and is known to be able to induce ligands for toll-like receptors (TLRs) and NOD, which is one of the pattern recognition receptors. Microbial metabolites such as short-chain fatty acids (SCFAs) or AhR ligands can directly act on intestinal cells and gut immune cells, but can also reach other organs through systemic circulation and regulate immunity. Many studies have shown that not pathogenic but coexisting microbiota can regulate the immune system, as described below.

Intestinal colonization of segmented filamentous bacteria promotes the differentiation of CD4+Th17 cells and induces signaling through the ILC3/IL-22/SAA1/2 axis, leading to IL-17A production by RORγt+Th17 cells. IL-22 derived from ILC3 facilitates IL-17A production by Th17 cells, contributing to the inhibition of certain microbial species. Decreased MHCII expression in ILC3 prevents the activation of commensal-specific CD4+ T cells, avoiding immune responses against the colonization of harmless microbes. Early-life microbial colonization partially inhibits the generation of abundant iNKT cells through sphingolipid production, preventing potential disease-promoting activities in the intestinal lamina propria and lungs.

Colonization by Bacteroides fragilis, a major constituent of the mammalian gut microbiota, promotes CD4+ T cell differentiation and contributes to balancing Th1 and Th2 in a polysaccharide A-dependent manner. Polysaccharide A is taken up by lamina propria dendritic cells via TLR2 and presented to naive CD4+ T cells, which differentiate into regulatory T cells (iTregs) in the presence of active TGF-β, and the IL-10 produced by these cells promotes immune homeostasis.

Maintaining this immune homeostasis also requires selectively maintaining appropriate gut microbes. Foxp3+ Tregs contributing to immune homeostasis are located in Peyer's patches and induce class switching in B cells, thereby maintaining and managing a microbial composition that can sustain bodily homeostasis.

The above results exemplify how the immune system and the coexisting microbial ecosystem influence each other. This suggests that after transplantation, the microbiome can affect T cells, B cells, and consequently impact and be impacted by the graft.

Conditions

Microbial Colonization

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Liver transplant patients

Patients who have undergone liver transplantation

gut microbiome

Intervention Type: OTHER

Obtaining new gut microbiome data in organ transplantation

Kidney transplant patients

Patients who have undergone kidney transplantation

gut microbiome

Intervention Type: OTHER

Obtaining new gut microbiome data in organ transplantation

Pancreas transplant patients

Patients who have undergone pancreas transplantation

gut microbiome

Intervention Type: OTHER

Obtaining new gut microbiome data in organ transplantation

Heart transplant patients

Patients who have undergone heart transplantation

gut microbiome

Intervention Type: OTHER

Obtaining new gut microbiome data in organ transplantation

Lung transplant patients

Patients who have undergone lung transplantation

gut microbiome

Intervention Type: OTHER

Obtaining new gut microbiome data in organ transplantation

Interventions

gut microbiome

Obtaining new gut microbiome data in organ transplantation

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Patients who have received or are receiving solid organ transplants (liver, kidney, pancreas, heart, lung) at this hospital.
• Patients who have listened to and understood a detailed explanation of this study, and have voluntarily decided to participate and provided written consent.

Exclusion Criteria

• Patients undergoing re-transplantation.
• Patients with a history of previous organ transplantation, except for cases where a pancreas transplant is performed after a kidney transplant.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Sei Won Lee

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

S2024-0859-0001

Identifier Type: -

Identifier Source: org_study_id