Altered Gut Microbiome Composition and Function in Individuals with Complex Regional Pain Syndrome.

Summary

In a two-site case-control study (53 CRPS vs 52 controls), CRPS was associated with altered gut taxa including short-chain fatty acid–metabolizing species and with differences in fecal and plasma short-chain fatty acid levels. Microbiome profiles alone accurately classified CRPS status in an independent cohort.

Key Findings

• Differential abundance in several bacterial taxa, including shifts in short-chain fatty acid–metabolizing species, in CRPS vs controls (53 vs 52).
• Targeted metabolomics confirmed differences in fecal and plasma short-chain fatty acid levels between groups.
• Machine learning based on microbiome composition accurately classified CRPS in a geographically independent validation cohort.

Clinical Implications

Immediate practice change is premature, but findings motivate consideration of diet/antibiotics/probiotics as potential modifiers in CRPS research and support developing microbiome-based diagnostics.

Limitations

• Observational cross-sectional design precludes causal inference
• Potential residual confounding from diet, medications, and lifestyle; 16S rRNA lacks strain-level/functional resolution compared to shotgun metagenomics

Future Directions

Longitudinal and interventional studies (dietary, probiotic/prebiotic, FMT) to test causality; shotgun metagenomics and metabolomics to define functional pathways and therapeutic targets.