Nanozyme-Enhanced Probiotic Spores Regulate the Intestinal Microenvironment for Targeted Acute Gastroenteritis Therapy

Abstract

Antibiotic therapeutics to combat intestinal pathogen infections often exacerbate microbiota dysbiosis and impair mucosal barrier functions. Probiotics are promising strategies, because they inhibit pathogen colonization and improve intestinal microbiota imbalance. Nevertheless, their limited targeting ability and susceptibility to oxidative stress have hindered their therapeutic potential. To tackle these challenges, Ces 3 is synthesized by in situ growth of CeO 2 nanozymes with positive charges on probiotic spores, facilitating electrostatic interactions with negatively charged pathogens and possessing a high reactive oxygen species (ROS) scavenging activity. Importantly, Ces 3 can resist the harsh environment of the gastrointestinal tract. In mice with S. Typhimurium-infected acute gastroenteritis, Ces 3 shows potent anti-S. Typhimurium activity, thereby alleviating the dissemination of S. Typhimurium into other organs. Additionally, owing to its O 2 deprivation capacity, Ces 3 promotes the proliferation of anaerobic probiotics, reshaping a healthy intestinal microbiota. This work demonstrates the promise of combining antibacterial, antiinflammatory, and O 2 content regulation properties for acute gastroenteritis therapy.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease

“…Inflammatory bowel disease (IBD) imposes a substantial burden on both patients and society. − As gut dysbiosis is closely involved in IBD, probiotics have recently gained considerable attention for IBD treatment owing to their gut microbiome-modulating capability. − Unfortunately, preserving the activity and colonization of probiotics in the inflammatory intestinal milieu remains challenging. − While modifying probiotics with functional coatings has been developed to enhance their viability and oral delivery, ,, the site-specific targeting of probiotics to the pathological lesions still faces challenges. Additionally, the elevated reactive oxygen species (ROS) in the microenvironment can deactivate probiotics and exacerbate inflammatory responses, propelling the progression of IBD. − Recently, nanomaterials with enzyme-like catalytic properties have garnered substantial interest for addressing inflammatory diseases. − The integration of nanozymes with probiotics or spores has emerged for treating gastrointestinal diseases. ,, However, the pH-varied enzyme activities and inadequate retention of nanocatalysts in intestine usually compromise their therapeutic benefits in IBD. − Furthermore, constructing nanozyme–probiotic systems typically involves synthesizing nanozymes separately and then attaching them to bacteria through covalent or noncovalent reactions. It is imperative to explore straightforward yet efficient strategies to seamlessly integrate nanocatalysts with probiotics and improve their targeting of inflamed lesions to maximize the benefits of each treatment module.…”