Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06405958
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-28
First Post:
2024-05-05
Brief Title:
Gut Microbiome Analysis in Organ Transplant Recipient
Sponsor:
Asan Medical Center
Organization:
Asan Medical Center
Study Overview
Official Title:
Analysis of Microbiome Changes and Prognostic Association After Solid Organ Transplantation
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Th1Th2 responses
Inducing regulatory T cells Tregs that promote immune homeostasis
Tregs in Peyers 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 grafts acceptance by affecting the recipients immune cells that respond to the transplant
In summary it highlights the microbiomes role in immune regulation and the potential for leveraging this interaction therapeutically including in the context of transplantation
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 Th1Th2 responses
Inducing regulatory T cells Tregs that promote immune homeostasis
Tregs in Peyers 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 grafts acceptance by affecting the recipients immune cells that respond to the transplant
In summary it highlights the microbiomes 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 CD4Th17 cells and induces signaling through the ILC3IL-22SAA12 axis leading to IL-17A production by RORγtTh17 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 Peyers 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
Intestinal colonization of segmented filamentous bacteria promotes the differentiation of CD4Th17 cells and induces signaling through the ILC3IL-22SAA12 axis leading to IL-17A production by RORγtTh17 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 Peyers 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None