Pingwei Powder alleviates high-fat diet-induced colonic inflammation by modulating microbial metabolites SCFAs

Area of Science:

• Integrative Medicine
• Gastroenterology
• Microbiome Research

Background:

• Ulcerative colitis (UC) is a chronic inflammatory condition with complex pathogenesis.
• Traditional Chinese Medicine (TCM), like Pingwei Powder (PWP), shows therapeutic potential for UC.
• The precise mechanisms of PWP in UC, particularly its interaction with the gut microbiota, require elucidation.

Purpose of the Study:

• To investigate the therapeutic effects of PWP on high-fat diet-induced colonic inflammation in a UC model.
• To explore the regulatory mechanisms of PWP on gut microbiota composition and function.
• To elucidate the role of the PI3K/AKT/mTOR pathway and autophagy in PWP's efficacy.

Main Methods:

• Network pharmacology identified potential PWP targets for UC.
• Histological, immunofluorescence, and Western blot analyses assessed colonic tissue changes and protein expression.
• qRT-PCR measured inflammatory cytokines; 16S rDNA sequencing and GC/MS analyzed gut microbiota and short-chain fatty acids (SCFAs); fecal microbiota transplantation (FMT) and butyrate supplementation validated mechanisms.

Main Results:

• PWP treatment downregulated PI3K, pAKT/AKT, and pmTOR/mTOR, indicating PI3K/AKT pathway inhibition.
• PWP enhanced colonic epithelial autophagy, evidenced by altered P62 and LC3B-II/LC3B-I levels.
• PWP increased the abundance of SCFA-producing bacteria (Alistipes, Parabacteroides) and elevated gut SCFA levels.

Conclusions:

• PWP effectively ameliorates colonic inflammation in UC by modulating gut microbiota and inhibiting the PI3K/AKT/mTOR pathway.
• Increased SCFA production, particularly butyrate, mediated by specific gut bacteria, is a key mechanism of PWP's therapeutic action.
• PWP promotes colonic autophagy, contributing to the resolution of inflammation and highlighting its potential as a novel therapeutic strategy for UC.