Gut Microbiome Analysis in Organ Transplant Recipient

Microbial Colonization Clinical Trial

Official title:

Analysis of Microbiome Changes and Prognostic Association After Solid Organ Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06405958
• Other study ID #: S2024-0859-0001
• Status: Not yet recruiting
• Start date: July 1, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Infections
• Microbial Colonization

Intervention

Other:
• gut microbiome
Obtaining new gut microbiome data in organ transplantation

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the gut Microbiome	Collecting admission and regular stool samples from solid organ transplant recipients (liver, kidney, heart, pancreas, lung) and performing high-resolution microbiome analysis (based on 16S full-length sequencing) to investigate changes in the gut microbiome following transplantation and develop models to predict outcomes in these patients.	3 years