Exploring the relationship between gut microbiota-metabolite axis and Jiawei Danxuan Koukang's therapeutic effects in male rats with oral submucous fibrosis: A multi-omics analysis.

OBJECTIVE

This work aims to explore how Jiawei Danxuan Koukang (JDK) ameliorates Oral Submucous Fibrosis (OSF) via regulating the gut microbiota and its metabolites.

DESIGN

We established an OSF rat model via oral mucosal arecoline injection. Rats were randomly divided into five groups: control, model, lycopene-treated, quercetin-treated, and JDK-treated. After intervention, we analyzed: serum metabolites by Liquid Chromatography-Mass Spectrometry -based untargeted metabolomics; gut microbiota profiling via 16S rDNA sequencing; oral mucosal histopathology and fibrosis using hematoxylin-eosin and Masson trichrome staining; expressions of fibrosis-related proteins (Transforming Growth Factor-β1 (TGF-β1), Collagen Type I Alpha 1 Chain (COL1A1)) by western blot; and cytokines (Interleukin-1β, Interleukin-6, Interleukin-10) in serum, oral and colon tissues via enzyme-linked immunosorbent assay.

RESULTS

In the OSF model group, 120 serum metabolites were upregulated and 39 were down-regulated. When comparing the JDK group with the model group, 83 metabolites were upregulated and 132 were downregulated in the JDK group. Specifically, JDK targeted key metabolites: prostaglandins, leukotrienes, lysophosphatidylcholine, and 4-hydroxyproline. JDK also regulated two critical metabolic pathways: gly-cine-serine-threonine metabolism and tryptophan metabolism. JDK reduces the pro-inflammatory Ruminococcus and restores the butyrate-producing Lachnospiraceae_NK4A136_group. JDK downregulated Interleukin-1β and Interleukin-6 levels systemically and locally, concurrently increasing Interleukin-10, and reduced the expression of fibrosis-related proteins (TGF-β1, COL1A1) in the oral mucosa.

CONCLUSIONS

JDK alleviates OSF by normalizing inflammation and fibrosis-related metabolic pathways, linking gut microbiota remodeling to metabolic homeostasis.