Decreasing of Trimethylamine N-Oxide by Cecal Microbiota and Choline-Trimethylamine Lyase are Associated with Sishen Pill on Diarrhea with Kidney-Yang Deficiency Syndrome.

BACKGROUND

Sishen Pill (SSP) is a traditional Chinese medicine prescription commonly used to treat diarrhea with kidney-yang deficiency syndrome. The aim was to investigate the underlying mechanisms of SSP's therapeutic effects, providing experimental evidence for its mechanism of action.

METHODS

A mouse model of diarrhea with kidney-yang deficiency syndrome was induced using adenine combined with . After successful model replication, SSP decoction was administered. CutC activity, TMAO, IL-6, TNF-α levels, and cecal content microbiota were measured.

RESULTS

SSP significantly improved the general behavioral characteristics of diarrhea mice, and reduced CutC activity, TMAO and IL-6 levels. Sequencing results indicated significant changes at the phylum and genus levels. Correlation analysis revealed a positive correlation between CutC activity and (<0.05) and (<0.05), and a significant negative correlation with (<0.05), (<0.05), (<0.05), and (<0.05). TNF-α levels showed a significant negative correlation with (<0.05), (<0.01), (<0.05), and (<0.05). IL-6 levels exhibited a significant negative correlation with (<0.05), (<0.05), (<0.05), (<0.01), and (<0.05), and a significant positive correlation with (<0.05), (<0.01), and . Serum TMAO levels showed a significant positive correlation with (<0.05) and (<0.01), and hepatic TMAO levels exhibited a significant positive correlation with (<0.05).

CONCLUSION

SSP significantly alleviated the symptoms of diarrhea with kidney-yang deficiency syndrome by modulating the cecal microbiota, downregulating CutC activity, and reducing TMAO and inflammatory factor levels. The cecal microbiota-CutC-TMAO-inflammatory cytokine axis may be a key mechanism underlying the therapeutic effects of SSP.