Colonization of Streptococcus pyogenes Is Associated with Functional Dyspepsia and Exacerbates Functional Dyspepsia in Mice by Inhibiting the RhoA/ROCK1 Pathway through the Skin-Gut Axis.

Abstract

Introduction: We investigated the importance of skin microbiota in functional dyspepsia (FD) based on the skin-gut axis theory and revealed potential mechanisms. This study also validates recent popular FD treatments.

Methods: We used mendelian randomization (MR) to analyze 418 gut bacteria and 145 skin bacteria, identifying key symbionts in FD development. Bibliometric keyword analysis was conducted on current FD therapies. Finally, we used a mouse model of FD to assess body weight, food intake, gastric residue rate, small intestine transit rate, and fecal water content after interventions with skin-gut symbionts and treatment methods. Hematoxylin-eosin staining observed gastric antrum tissue morphology. RhoA and ROCK1 protein and mRNA levels in gastric antrum tissue were detected by western blot and real-time PCR. Fluorescence immunoassay observed ROCK1 and vesicular acetylcholine transporter (VAChT) protein expression.

Results: Streptococcus has a causal relationship with FD. Bibliometric analysis highlighted electroacupuncture as a research hotspot. Skin Streptococcus colonization reduced food intake, body weight, small intestine transit rate, and increased gastric residue rate in FD mice, decreasing RhoA, ROCK1, and VAChT protein and mRNA levels. Antibiotics reversed these effects. Electroacupuncture improved weight, appetite, gastrointestinal motility, and RhoA, ROCK1, and VAChT protein, and mRNA levels in FD mice.

Conclusion: The study confirmed the pathogenic role of skin Streptococcus in FD and the therapeutic value of electroacupuncture at Tianshu acupoint, potentially via RhoA/ROCK1 signaling pathway regulation.