235: Gut Microbiome Composition Associated with Post-Surgical Pain: A Systematic Review

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic postsurgical pain, Developing methodology/technology, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics), Pain in Special Populations

Background and Aims: Post-surgical pain reduces quality of life and increases healthcare costs. Approximately 10-50% of surgical patients develop Persistent Post-Surgical Pain (PPSP), defined as new or worsening pain persisting >3 months post-operatively. The mechanisms underlying individual variability in pain sensitization after surgery remain incompletely understood, limiting identification of high-risk patients. The gut microbiome comprises thousands of bacterial species, which have been associated with multiple pain conditions through gut-derived metabolites. This systematic review examined whether gut microbiome composition differs between patients who develop PPSP and controls. Secondary objectives assessed microbiome differences in acute post-surgical pain (<7 days post-surgery).

Methods: Inclusion criteria were (1) observational studies (2) in adults undergoing surgery (3) that assessed development of acute or persistent post-surgical pain and (4) examined the gut microbiome and its metabolites (5) published through August 2025. Searches were conducted in MEDLINE, Embase, Web of Science Core Collection, BIOSIS Previews, medRxiv, and CENTRAL through August 26, 2025. Study quality and risk of bias were assessed using the Newcastle-Ottawa Scale and GRADE. Qualitative synthesis was performed due to heterogeneity in study design, populations, pain measures, and microbiome analysis techniques.

Results: Two independent reviewers screened 5,351 studies; 6 observational studies (N=290 participants) met inclusion criteria. Three studies examined acute post-surgical pain exclusively, one examined PPSP exclusively, and two examined both acute and persistent post-surgical pain. Three studies found no significant difference in alpha diversity between patients who developed PPSP and controls. Beta diversity findings were inconsistent: two of three studies found significant differences. For acute post-surgical pain, alpha diversity measures showed inconsistent findings across studies; whereas beta diversity did not differ significantly. We identified commonly reported bacterial taxa and compared their associations with post-surgical pain across studies.

Conclusions: Limitations included the small number of heterogeneous studies, insufficient statistical power, and two studies' postoperative sampling precluded preoperative microbiome assessment. Nevertheless, this review identifies best practices in microbiome-pain research by systematically comparing methodologies. Sequencing approaches vary widely; 16S rRNA gene sequencing lacks the phylogenetic resolution provided by shotgun metagenomic sequencing, which captures species-level shifts and functional potential. Future research should prioritize multi-omic integration; one study correlated microbiome composition with metabolite profiles to provide mechanistic insights into pain sensitization. Moving beyond preliminary associations requires larger, well-powered cohorts and high-resolution sequencing to validate the gut microbiome as a viable biomarker for PPSP.

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Presenting Author: Stephanie Ponsonby
Submitting Author: Stephanie Ponsonby

Senior Author: Shiqian Shen

IASP 2026 Global Year theme of Neuropathic Pain: No

• Shiqian Shen: MD PHD - Massachusetts General Hospital
• Kristin Schreiber: MD PHD - Stanford University
• Stephanie Friree-Ford - Harvard University
• Dennis Muñoz-Vergara: DVM MSci PHD - Harvard University