Potential application of brain-gut axis-based treatments in Long COVID and ME/CFS: a case-based systematic review.

Observed Findings

• Synbiotic and herbal interventions showed benefits for fatigue or post-exertional malaise with associated changes in specific bacterial populations
• Transcranial direct current stimulation combined with exercise improved fatigue outcomes, while standalone tDCS showed limited efficacy
• Electroacupuncture-based deep peroneal nerve stimulation in one patient produced significant total fatigue reduction with early improvements in motivation and mental fatigue
• Peripheral and auricular TENS demonstrated limited efficacy as standalone interventions for ME/CFS fatigue
• Brain-gut axis interventions may modulate neuroinflammation, restore microbiome balance, and improve intestinal barrier function based on mechanism review

Inferred Conclusions

• Brain-gut axis dysregulation represents a targetable pathophysiological pathway in ME/CFS and Long COVID
• Neuromodulation approaches may be more effective when combined with complementary therapies than when used alone
• Vagal stimulation via electroacupuncture represents a potentially feasible option for patients with severe or treatment-resistant symptoms
• Multiple mechanistic pathways—including microbiome restoration, neuroinflammation reduction, and epithelial barrier repair—likely contribute to fatigue improvement with these interventions

Remaining Questions