Lacto-N-Triose II Alleviates DSS-Induced Colitis via Gut Microbiota and Metabolites Associated with the PI3K-Akt Pathway.

LNT II significantly alleviated disease pathology in DSS-induced colitis.

• LNT II is a core component of human milk oligosaccharides (HMOs) and was tested in a dextran sodium sulfate (DSS)-induced colitis mouse model.
• LNT II treatment significantly reduced colitis-associated disease pathology compared to DSS-treated controls.
• Restoration of epithelial barrier integrity was observed following LNT II administration.
• LNT II modulated inflammatory responses in the colitis model.

LNT II reversed colitis-induced gut microbial dysbiosis.

• DSS-induced colitis caused gut microbiota dysbiosis, which was reversed by LNT II treatment.
• LNT II remodeled the composition and/or abundance of gut microbial communities.
• The study used a multiomics approach to characterize microbiota changes.
• Gut microbiota remodeling was identified as part of a mechanistic cascade linking LNT II to its anti-inflammatory effects.

LNT II altered key metabolites associated with its therapeutic effects.

• LNT II altered levels of D-xylulosonic acid, Sakacin P, and taurocholic acid in DSS-induced colitis.
• These metabolites were identified as key mediators in the microbiota-metabolite-immune network regulated by LNT II.
• Metabolomic analysis was integrated with transcriptomic and microbiota data in a multiomics framework.
• Regulation of these specific metabolites was linked to downstream inhibition of the PI3K-Akt signaling pathway.

Transcriptomic analysis revealed that LNT II suppresses colonic inflammation via the PI3K-Akt signaling pathway.

• Transcriptomic profiling identified the PI3K-Akt signaling pathway as the primary pathway modulated by LNT II in colitis.
• LNT II inhibited PI3K-Akt pathway activity to alleviate colitis-associated inflammation.
• This finding was corroborated by integrated multiomics analysis establishing a mechanistic cascade.
• The PI3K-Akt pathway was linked upstream to gut microbiota remodeling and metabolite regulation by LNT II.

Integrated multiomics analysis established a complete mechanistic cascade by which LNT II exerts its therapeutic effects.

• The mechanistic cascade identified was: LNT II remodels gut microbiota → regulates specific metabolites → inhibits the PI3K-Akt pathway → alleviates colitis.
• The analysis integrated transcriptomics, metabolomics, and microbiota profiling.
• The cascade represents systematic regulation of the 'microbiota-metabolite-immune network' by LNT II.
• These findings provide 'comprehensive experimental evidence supporting LNT II as a novel prebiotic therapy for UC.'