Gut microbiota and acute rejection in solid organ transplantation

Area of Science:

• Microbiology
• Immunology
• Transplantation Science

Background:

• The gut microbiota plays a crucial role in modulating host immune responses.
• Dysbiosis, an imbalance in the gut microbiota, is increasingly associated with adverse outcomes in solid organ transplantation.
• Understanding the mechanistic links between microbial dysbiosis and acute allograft rejection is critical for improving graft survival.

Purpose of the Study:

• To review recent advances in understanding the relationship between the microbiota and acute allograft rejection.
• To explore the potential of microbial and metabolic interventions in transplantation.

Main Methods:

• Review of clinical observations and experimental models investigating microbiota-immune interactions in transplantation.
• Analysis of studies examining microbial diversity, specific taxa, and metabolites in relation to acute rejection.
• Examination of the impact of microbial alterations on immune priming and effector phases.

Main Results:

• Reduced gut microbial diversity and loss of short-chain fatty acid (SCFA)-producing bacteria often precede acute rejection in solid organ transplant recipients.
• Experimental models demonstrate that specific bacterial strains or SCFA supplementation can prolong graft survival.
• Elevated levels of lysophosphatidic acid (LPA), a bacterial metabolite, are associated with allograft rejection.
• Microbial and metabolic dysregulation can influence both the priming and effector phases of the alloimmune response.

Conclusions:

• Microbial dysbiosis can precede acute allograft rejection, with some microbial components being protective and others detrimental.
• Targeting microbial communities or their metabolites offers potential therapeutic strategies.
• Combined therapeutic targeting of microbial axes may yield additive or synergistic benefits in modulating the alloimmune response and improving graft outcomes.