Acid-base transformative HADLA micelles alleviate colitis by restoring adaptive immunity and gut microbiome

Area of Science:

• Gastroenterology
• Nanomedicine
• Immunology

Background:

• Inflammatory bowel disease (IBD) presents a growing global health challenge with limited curative treatments.
• Current IBD therapies suppress immune responses, leading to side effects like infections and cancers.
• There is a need for novel, safe, and effective IBD treatments with improved delivery methods.

Purpose of the Study:

• To develop and evaluate an orally administered nanotherapeutic micelle (HADLA) for IBD treatment.
• To assess HADLA's efficacy, safety, and mechanism of action in a murine colitis model.
• To explore HADLA's potential for modulating the immune system and gut microbiome in IBD.

Main Methods:

• Conjugation of hyaluronic acid (HA) and dehydrolithocholic acid (DLA) to form HADLA nanotherapeutic micelles.
• Administration of HADLA via oral gavage in a murine model of colitis.
• Evaluation of therapeutic efficacy, including targeting of inflammatory tissues, restoration of intestinal barrier function, and reduction of cell death.
• Assessment of immune modulation, focusing on T helper 17 (Th17) cell activation.
• Analysis of gut microbiome composition, including changes in beneficial probiotics and pathogenic bacteria.

Main Results:

• HADLA demonstrated satisfactory therapeutic efficacy in a murine colitis model with a full safety profile.
• HADLA effectively targeted inflammatory colon tissues, restored intestinal barrier function, and reduced epithelial cell death.
• HADLA inhibited pathogenic T helper 17 (Th17) cell activation, showing superior efficacy to DLA alone.
• HADLA modulated the gut microbiome, increasing beneficial probiotics and decreasing pathogenic bacteria like Turicibacter.

Conclusions:

• Orally administered HADLA nanotherapeutic micelles represent a promising new therapeutic strategy for IBD.
• HADLA offers a safe and effective approach to IBD treatment by targeting inflammation, restoring gut integrity, and modulating the immune system and microbiome.
• This study highlights the potential of oral nanomedicine for IBD and introduces DLA as a potential therapeutic agent for IBD treatment.