Citrus-Derived Exosome-like Nanoparticles Attenuate High-Fat Diet-Aggravated Colitis by Gut Microbiota-Metabolites Modulation.

CELNs effectively ameliorated HFD-aggravated colitis by improving disease activity, colon length, and immune organ index.

• CELNs were evaluated as a dietary intervention in a high-fat diet-aggravated colitis model.
• Improvements were observed across multiple clinical indicators including disease activity index, colon length, and immune organ index.
• HFD is described as a recognized risk factor that exacerbates intestinal inflammation and complicates colitis pathology.

CELNs restored gut barrier integrity by upregulating tight junction proteins occludin and ZO-1.

• Both occludin and ZO-1 were upregulated following CELN treatment.
• Restoration of gut barrier integrity was identified as a key mechanistic pathway of CELN action.
• Gut barrier disruption is a hallmark feature of HFD-aggravated colitis that CELNs were able to reverse.

CELNs suppressed oxidative stress and pro-inflammatory signaling in HFD-aggravated colitis.

• Suppression of oxidative stress was identified as one of the mechanistic actions of CELNs.
• Pro-inflammatory signaling pathways were also suppressed by CELN treatment.
• These effects were observed in the context of HFD-exacerbated colitis.

CELNs rebuilt microbial dysbiosis by enriching beneficial bacterial taxa, specifically Faecalibaculum and Bacteroides.

• CELN treatment led to enrichment of Faecalibaculum and Bacteroides in the gut microbiota.
• Microbial dysbiosis was identified as a key feature of HFD-aggravated colitis that CELNs were able to rectify.
• Restoration of microbial community structure was linked to downstream metabolic improvements.

CELNs normalized critical metabolic pathways by increasing short-chain fatty acid production in HFD-aggravated colitis.

• Short-chain fatty acid production was increased following CELN treatment.
• Increased SCFA production was one of several metabolic pathway normalizations observed.
• This metabolic change was associated with the restoration of beneficial gut microbiota.

CELNs reshaped bile acid profiles by increasing chenodeoxycholic acid and deoxycholic acid content.

• Both chenodeoxycholic acid and deoxycholic acid were specifically identified as increased following CELN treatment.
• Reshaping of bile acid profiles was identified as one component of CELN-mediated metabolic normalization.
• Altered bile acid metabolism is a feature of the HFD-aggravated colitis model that CELNs were able to modify.

CELNs promoted anti-inflammatory indole derivatives, especially indole acrylic acid, and modulated branched-chain amino acid metabolism.

• Indole acrylic acid was specifically identified as the most notable anti-inflammatory indole derivative increased by CELN treatment.
• Branched-chain amino acid metabolism was also modulated by CELNs.
• Promotion of anti-inflammatory indole derivatives represented an additional mechanistic pathway linking microbiota changes to inflammation suppression.