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

DHP significantly alleviated UC symptoms and reduced colonic tissue damage in mice while restoring intestinal microbiota balance.

• Animal model of ulcerative colitis was used to validate preventive effects of DHP
• DHP treatment restored balance of intestinal microbiota as assessed by 16S rRNA sequencing
• Colonic tissue damage was assessed histologically
• The study used a preventive treatment design in the mouse model

DHP substantially increased the concentration of short-chain fatty acids (SCFAs) in the colon of UC mice.

• SCFAs were detected by LC-MS/MS methodology
• Increased SCFA concentrations were observed in colon tissue following DHP treatment
• The increase in SCFAs was associated with shifts in gut microbiota composition
• SCFA elevation was identified as a key mediator of DHP's therapeutic mechanism

DHP activated PPARγ and inhibited NF-κB phosphorylation in colon tissue, effectively reducing inflammation.

• PPARγ/NF-κB pathway protein expression was assessed by immunofluorescence and Western blotting
• DHP treatment triggered PPARγ activation in colon tissue
• NF-κB phosphorylation was inhibited following DHP treatment
• These pathway changes were associated with reduced colonic inflammation and improved UC outcomes

Fecal microbiota transplantation (FMT) experiments confirmed that the preventive benefits of DHP are mediated through the intestinal flora.

• FMT experiments were conducted to validate the gut microbiota-dependent mechanism of DHP
• Transplantation of fecal microbiota from DHP-treated animals conferred protective effects
• FMT results confirmed that gut microbiota modulation is a primary mechanism of DHP action
• This experiment provided direct evidence linking DHP's effects to microbial changes rather than direct host tissue effects

Lachnoclostridium edouardi was identified as a DHP-specifically regulated strain associated with SCFA production.

• Key gut microbiota affected by DHP were identified using 16S rRNA sequencing
• Lachnoclostridium edouardi was found to be specifically regulated by DHP among the differential intestinal flora
• This strain was found to be related to the production of SCFAs
• In vitro fermentation experiments were conducted to investigate the effect of DHP fermented by this strain on colonic epithelial cell inflammation

In vitro fermentation of DHP by Lachnoclostridium edouardi produced markedly higher SCFA content and effectively suppressed inflammation in colonic epithelial cells.

• In vitro fermentation experiments were used to assess metabolite production by Lachnoclostridium edouardi with DHP as substrate
• SCFA content in fermentation metabolites was markedly higher when DHP was fermented by Lachnoclostridium edouardi
• Metabolites produced by DHP fermentation with this strain effectively suppressed inflammation in colonic epithelial cells
• These findings clarified Lachnoclostridium edouardi as the specific intestinal strain regulated by DHP responsible for SCFA-mediated anti-inflammatory effects

Dendrobium huoshanense polysaccharides (DHP) is an active ingredient of Dendrobium huoshanense with multiple pharmacological activities relevant to gastrointestinal disorders.

• Dendrobium huoshanense (DH) has a long history of medicinal use in treatment of gastrointestinal disorders
• DH has therapeutic effects on chronic atrophic gastritis, superficial gastritis, and duodenal ulcer
• DH promotes gastric juice secretion and gastrointestinal motility
• DHP is extracted from DH and has a variety of pharmacological activities