Pain syndromes in transplantation: the role of the gut microbiome

The purpose of this review is to discuss common pain phenotypes in transplantation, summarize known gut microbiome features associated with chronic pain, and to map known gut microbiome features in transplantation with diagnosis-independent pain features.

Persistent pain is common across solid organ and hematopoietic stem cell transplantation, arises from diverse mechanisms, and often extends well beyond the perioperative period. Growing evidence supports the gut microbiome as a biologically plausible modulator of chronic pain across disease states, including transplantation. Alterations in microbial diversity, microbial metabolites, intestinal barrier integrity, and neuroimmune signaling have been linked to pain amplification and central sensitization across multiple chronic pain conditions. In transplant populations, exposure to immunosuppressive therapies, antibiotics, metabolic comorbidities, and other transplant-related stressors creates a unique environment for sustained microbiome disruption that may contribute to persistent symptom burden.

Collectively, these data highlight the importance to systematically assess and manage pain as a core transplant outcome rather than a secondary concern, and to highlight the potential role of the gut microbiome as a risk screening tool or a therapeutic target for pain interventions. Although mechanistic and observational data support biologic plausibility, transplant-specific microbiome-pain evidence remains preliminary and warrants longitudinal investigation.