Journal Article

H2S‐Releasing Versatile Montmorillonite Nanoformulation Trilogically Renovates the Gut Microenvironment for Inflammatory Bowel Disease Modulation

Jin, Ting, Shi, Jiayi, Zhang, Yanmei, Wang, Xianwen, Zeng, Youyun, Chen, Dongfan, Shen, Xinkun, Zhou, Qiang, Lu, Hongyang, Cai, Xiaojun

2024

Overview

Abnormal activation of the intestinal mucosal immune system, resulting from damage to the intestinal mucosal barrier and extensive invasion by pathogens, contributes to the pathogenesis of inflammatory bowel disease (IBD). Current first‐line treatments for IBD have limited efficacy and significant side effects. An innovative H2S‐releasing montmorillonite nanoformulation (DPs@MMT) capable of remodeling intestinal mucosal immune homeostasis, repairing the mucosal barrier, and modulating gut microbiota is developed by electrostatically adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels (DATS@PDNs, abbreviated as DPs) onto the montmorillonite (MMT) surface. Upon rectal administration, DPs@MMT specifically binds to and covers the damaged mucosa, promoting the accumulation and subsequent internalization of DPs by activated immune cells in the IBD site. DPs release H2S intracellularly in response to glutathione, initiating multiple therapeutic effects. In vitro and in vivo studies have shown that DPs@MMT effectively alleviates colitis by eliminating reactive oxygen species (ROS), inhibiting inflammation, repairing the mucosal barrier, and eradicating pathogens. RNA sequencing revealed that DPs@MMT exerts significant immunoregulatory and mucosal barrier repair effects, by activating pathways such as Nrf2/HO‐1, PI3K‐AKT, and RAS/MAPK/AP‐1, and inhibiting the p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways, as well as glycolysis. 16S rRNA sequencing demonstrated that DPs@MMT remodels the gut microbiota by eliminating pathogens and increasing probiotics. This study develops a promising nanoformulation for IBD management. An H2S‐releasing montmorillonite nanoformulation (DPs@MMT) is developed by adsorbing diallyl trisulfide‐loaded peptide dendrimer nanogels onto the MMT surface. DPs@MMT can remodel intestinal mucosal immune homeostasis by activating Nrf2/HO‐1 and PI3K‐AKT pathways, inhibiting p38/ERK MAPK, p65 NF‐κB, and JAK‐STAT3 pathways along with HIF‐1‐induced glycolysis; repair mucosal barrier by activating RAS/MAPK/AP‐1 pathway; and modulate gut microbiota by eliminating pathogens and increasing probiotics.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adsorption / Antioxidants / Apoptosis / Biocompatibility / Chemokines / Chronic illnesses / colitis / Cytokines / Efficiency / Gases / gut microbiota / Homeostasis / hydrogen sulfide gas therapy / immunoregulation / Inflammation / Inflammatory bowel disease / Microbiota / Morphology / peptide dendrimer nanogel / Permeability / Physiology / Ratios / Repair & maintenance / Tumor necrosis factor-TNF