Gut Microbiome Analysis in Organ Transplant Recipient

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.

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.