The gut microenvironment in antibody-mediated rejection: from conventional immunosuppression to precision...

The gut microbiota and broader gut microenvironment, comprising microbiota-derived metabolites and host-microbial interactions, have emerged as potentially modifiable factors associated with host immune regulation and have been implicated in altered drug responsiveness, immune-mediated diseases, and metabolic disorders. Accumulating evidence suggests that the gut microenvironment may modulate post-transplant immune responses and may provide candidate biomarkers and therapeutic targets in organ transplantation. Gut dysbiosis has been associated with immune dysregulation and adverse allograft outcomes, although direct causal evidence in human AMR remains limited. Profiling the gut microenvironment may therefore complement conventional immune monitoring for post-transplant risk stratification. In this review, current evidence on the interactions among the gut microbiota, microbiota-derived metabolites, and host immune regulation is synthesized, with particular emphasis on the role of the gut microenvironment in maintaining immune homeostasis and influencing transplant outcomes. The impact of alterations in the gut microenvironment on the development of antibody-mediated rejection-a major barrier to long-term graft survival-is examined by focusing on their effects on regulatory immune pathways and inflammatory responses. The potential role of microbiota-derived metabolites in promoting immune tolerance and graft accommodation, two complementary mechanisms that contribute to long-term allograft protection, is also discussed. Finally, gut microenvironment-based strategies for early diagnosis, risk stratification, and rejection prediction are evaluated, alongside therapeutic interventions including prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These strategies may facilitate pre-emptive intervention before irreversible graft injury develops and support a shift from conventional immunosuppression towards precision immunomodulation in transplantation medicine.