Oral Bacterial Predator with "Catch-and-Kill" Functionality for Bacterial Enteritis via Selective Pathogen Capture and Sonodynamic Elimination.

Abstract

Bacterial enteritis necessitates innovative therapeutic strategies to overcome the significant limitations posed by conventional antibiotics. Here, we introduce a pioneering antibacterial approach, employing a multifaceted "catch-and-kill" mechanism that synergistically integrates targeted pathogen capture, sonodynamic eradication, and toxin neutralization. We present SonoMMT, a microfluidically engineered sonosensitizer-montmorillonite complex. SonoMMT selectively adsorbs pathogenic bacteria and bacterial toxins, shields encapsulated sonosensitizers from gastric degradation, and enables sonodynamic therapy. Upon ultrasound activation, SonoMMT generates localized reactive oxygen species (ROS), efficiently eliminating captured pathogens and neutralizing residual toxins while preserving host cell integrity. In vitro assessments demonstrate robust antibacterial efficacy against bacteria. In vivo studies using a <i>Salmonella typhimurium</i> (<i>S. typhimurium</i>)-induced enteritis mouse model confirm that orally delivered SonoMMT significantly reduces bacterial loads, toxin levels, intestinal inflammation, and tissue damage. Moreover, gut microbiome analysis reveals beneficial shifts in microbial composition post-treatment, underscoring SonoMMT's dual action in pathogen clearance and microbiome restoration. Thus, SonoMMT represents a transformative advancement in bacterial enteritis management.