Mechanistic study of Dendrobium huoshanense polysaccharides improving ulcerative colitis by promoting Lachnoclostridium edouardi metabolism of short-chain fatty acids.

ETHNOPHARMACOLOGICAL RELEVANCE: Dendrobium huoshanense C. Z. Tang et S. J. Cheng (DH) is a traditional medicinal herb with a long history of medicinal use in the treatment of gastrointestinal disorders. It has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer, while also promoting gastric juice secretion and gastrointestinal motility. Dendrobium huoshanense polysaccharides (DHP) is an active ingredient extracted from it and has a variety of pharmacological activities, but its mechanism of action on ulcerative colon is worthy of further study.

AIMS OF THIS STUDY: This study aimed to investigate whether DHP could alleviate ulcerative colitis (UC) by activating PPARγ and to elucidate the mechanism behind it in relation to the short-chain fatty acid (SCFAs) content metabolized by gut microbiota.

METHODS: This study initially validated the preventive effects of DHP on UC using an animal model. The key gut microbiota affected by DHP were identified by 16S rRNA. The potential mechanism of DHP treatment for UC was demonstrated by LC-MS/MS to detect the levels of SCFAs, and by immunofluorescence and Western blotting to detect the expression of PPARγ/NF-κB pathway proteins. This potential mechanism was further confirmed by a fecal microbiota transplantation (FMT) experiment. Finally, through the in-depth study of the different intestinal flora regulated by DHP, Lachnoclostridium edouardi was found to be related to the production of SCFAs, and the effect of metabolites produced by DHP fermented by this strain on the inflammation of colonic epithelial cells was investigated through in vitro fermentation experiments, to clarify the intestinal strains that are specifically regulated by DHP.

RESULTS: The results showed that DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice, while restoring the balance of the intestinal microbiota. In addition, DHP substantially increased the concentration of SCFAs in the colon. These shifts triggered PPARγ activation and inhibited NF-κB phosphorylation in the colon tissue, effectively reducing inflammation and improving UC outcomes. The FMT assay further validated that the preventive benefits of DHP were mediated through the intestinal flora. Meanwhile, the DHP-specifically regulated strain Lachnoclostridium edouardi showed markedly higher short-chain fatty acid content in metabolites produced by fermentation with DHP in vitro and effectively suppressed inflammation in colonic epithelial cells.

CONCLUSIONS: This study suggests that DHP can play a role in the treatment of UC by modulating short-chain fatty acid metabolism in the gut microbiota and activating the PPARγ/NF-κB pathway. Moreover, DHP was able to promote the content of SCFAs produced by the metabolism of the Lachnoclostridium edouardi strain in the gut microbiota, and its metabolites also showed therapeutic effects on UC. These findings provide a basis for the clinical application of DHP in UC.