Shaoyao Gancao decoction alleviates functional constipation by inhibiting Escherichia-Shigella expansion, modulating gut microbiota, and suppressing dysbiosis-induced endocannabinoid production: evidence from a self-controlled pilot study.

Introduction: Shaoyao Gancao Decoction (SGD), a classical traditional Chinese medicine formula, has been clinically reported to improve symptoms of functional constipation (FC), although its underlying mechanisms remain unclear. This study aimed to explore the clinical efficacy and gut microbiota modulation of SGD in patients with FC. Methods: A self-controlled pilot study was conducted in 20 patients diagnosed with FC according to the Rome III (IV) criteria. Participants received a 3-5 day oral intervention with SGD. Clinical outcomes, including stool frequency, consistency, and ease of defecation, were evaluated using self-reported questionnaires. Fecal samples collected before and after treatment were analyzed for microbial composition (16S rRNA sequencing) and short-chain fatty acids (SCFAs). Results: Ninety percent of participants reported symptomatic improvement, with 70% achieving increased stool frequency (> 3 times/week). SGD treatment markedly shifted the fecal microbiota from a dysbiotic state dominated by Proteobacteria, Enterobacteriaceae, and Escherichia-Shigella to a community enriched in Firmicutes, Veillonella, Roseburia, and Ruminococcus. These microbial changes were accompanied by significant increases in fecal SCFAs and improvements in stool consistency and frequency. Functional prediction analysis revealed that SGD suppressed unsaturated fatty acid and arachidonic acid metabolism, thereby attenuating retrograde endocannabinoid signaling associated with intestinal hypomotility. Feature taxa enriched in responders-such as Ruminococcus sp. N15.MGS-57 and Bacteroides coprophilus-were linked to enhanced estrogen activity and secondary bile acid metabolism. Discussion: These findings suggest that SGD alleviates FC by restoring microbial balance, enhancing SCFA production, and suppressing dysbiosis-induced endocannabinoid signaling. As a pilot study, the results are preliminary but provide mechanistic insights that warrant validation in larger, randomized controlled trials.