Enzyme-like biomimetic oral-agent enabling modulating gut microbiota and restoring redox homeostasis to treat inflammatory bowel disease

Abstract

Reactive oxygen species (ROS), immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease (IBD). Herein, a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed, using yeast cell wall (YCW) as the outer shell and zinc-doped Prussian blue analogue (ZnPBA) nanozyme inside. When orally administered, the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E. coli, meanwhile exhibiting improved intestinal epithelial barrier repair. Moreover, it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway. More importantly, the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity, significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E. coli to the same level as normal mice. Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

Graphical abstract

A novel enzyme-like biomimetic oral-agent ZnPBA@YCW could successfully regulate gut flora by significantly downgrading Escherichia coli's occupied ecological niche, enhancing the bacterial biodiversity while increasing the abundance of probiotics with anti-inflammatory phenotype. Moreover, it breaks the vicious cycle of ROS-inflammation, making it a highly efficient treatment option for treating inflammatory bowel disease.

Highlights

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  A novel enzyme-like oral-agent ZnPBA@YCW has been developed for the first time, using YCW as the outer shell and ZnPBA nanozyme inside.

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  ZnPBA@YCW is able to adhere to E. coli and subsequently releases ZnPBA nanozyme for removal of E. coli.

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  ZnPBA@YCW exhibits remarkable capability in restoring redox homeostasis.

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  ZnPBA@YCW can effectively regulate gut microbiome .