Microbial ColonizationNCT06405958
Gut Microbiome Analysis in Organ Transplant Recipient
An observational study of Microbial Colonization, run by Asan Medical Center.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Microbial Colonization
- What is being tested?
- gut microbiome
- How many people
- 200 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2024to 31 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
About this study
Official title: 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
Read more
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.
Read the 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
- Being tested
- gut microbiome
- Keywords
- microbiota, solid organ transplantation, metagenomic sequencing
- Medical subject headings
- Communicable Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gut microbiomeOther
Obtaining new gut microbiome data in organ transplantation
| Study group | Role | What they receive |
|---|---|---|
| Liver transplant patients | Patients who have undergone liver transplantation Receives: Other: gut microbiome | |
| Kidney transplant patients | Patients who have undergone kidney transplantation Receives: Other: gut microbiome | |
| Pancreas transplant patients | Patients who have undergone pancreas transplantation Receives: Other: gut microbiome | |
| Heart transplant patients | Patients who have undergone heart transplantation Receives: Other: gut microbiome | |
| Lung transplant patients | Patients who have undergone lung transplantation Receives: Other: gut microbiome |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2024
- Study start1 Jul 2024 (estimated)
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Microbial ColonizationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sei Won Lee, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06405958
- Sponsor's protocol ID
- S2024-0859-0001
- Status last verified
- May 2024
- First submitted
- 5 May 2024
- Last updated
- 28 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of Microbiome Changes and Prognostic Association After Solid Organ Transplantation
- ClinicalTrials.gov ID
- NCT06405958
- Acronym / sponsor ID
- S2024-0859-0001
- Conditions
- Microbial Colonization
- Keywords
- microbiota, solid organ transplantation, metagenomic sequencing
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- 1 Jul 2024 (estimated)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 9 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Liver transplant patients | – | Other: gut microbiomePatients who have undergone liver transplantation |
| Kidney transplant patients | – | Other: gut microbiomePatients who have undergone kidney transplantation |
| Pancreas transplant patients | – | Other: gut microbiomePatients who have undergone pancreas transplantation |
| Heart transplant patients | – | Other: gut microbiomePatients who have undergone heart transplantation |
| Lung transplant patients | – | Other: gut microbiomePatients who have undergone lung transplantation |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gut microbiomeObtaining new gut microbiome data in organ transplantation | Other | Heart transplant patients, Kidney transplant patients, Liver transplant patients, Lung transplant patients, Pancreas transplant patients |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
An observational study of Microbial Colonization, run by Asan Medical Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the gut Microbiome (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2024.