Gut Microbiome Analysis in Organ Transplant Recipient

May 24, 2024 updated by: Sei Won Lee, Asan Medical Center

Analysis of Microbiome Changes and Prognostic Association After Solid Organ Transplantation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

For liver transplant patients, 90 samples are expected with stool, blood, and saliva collection at baseline, 1 month, and 6-12 months post-transplant. 16S full-length sequencing will be performed on these samples. For kidney transplant recipients, 70 stool samples will undergo the same collection timing and 16S analysis. Heart transplant patients will contribute 10 stool samples following the same timepoints for 16S sequencing and RNA sequencing. Lung transplant recipients will provide 15 stool and blood samples at those timepoints for 16S full-length and RNA sequencing analysis. Finally, 15 stool and blood samples will be collected from pancreas transplant recipients per the stated schedule for 16S analysis only. The comprehensive sampling strategy across different organ groups aims to characterize microbiome and transcriptomic changes over the transplant period using appropriate molecular profiling methods.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Liver transplant patients
Patients who have undergone liver transplantation
Other: gut microbiome
Obtaining new gut microbiome data in organ transplantation
Kidney transplant patients
Patients who have undergone kidney transplantation
Other: gut microbiome
Obtaining new gut microbiome data in organ transplantation
Pancreas transplant patients
Patients who have undergone pancreas transplantation
Other: gut microbiome
Obtaining new gut microbiome data in organ transplantation
Heart transplant patients
Patients who have undergone heart transplantation
Other: gut microbiome
Obtaining new gut microbiome data in organ transplantation
Lung transplant patients
Patients who have undergone lung transplantation
Other: gut microbiome
Obtaining new gut microbiome data in organ transplantation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Changes in the gut Microbiome
Time Frame: 3 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Asan Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 5, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 28, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S2024-0859-0001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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