Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment

J Control Release. 2024 Oct:374:140-153. doi: 10.1016/j.jconrel.2024.07.071. Epub 2024 Aug 14.

Abstract

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.

Keywords: Depleted mucus; Hydrogen sulfide; Inflammatory bowel disease; Montmorillonite; Probiotics colonization.

MeSH terms

  • Animals
  • Bentonite*
  • Colitis* / chemically induced
  • Colitis* / therapy
  • Dextran Sulfate*
  • Escherichia coli*
  • Gastrointestinal Microbiome*
  • Humans
  • Hydrogen Sulfide* / metabolism
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Intestines / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Mucus* / metabolism
  • Probiotics* / administration & dosage
  • Probiotics* / therapeutic use

Substances

  • Bentonite
  • Hydrogen Sulfide
  • Dextran Sulfate