Decolonizing the gut from multidrug-resistant bacteria: Current strategies and future perspectives

Abstract

The rise of multidrug-resistant organisms (MDROs) represents a serious global health crisis, with the gastrointestinal tract serving as a major reservoir for these pathogens. This review highlights the burden of gut colonization by MDROs, its role in spreading antimicrobial resistance, and explores current and emerging strategies for decolonization. Various non-antibiotic approaches such as probiotics, prebiotics, bacterial consortia, selective digestive decontamination, faecal microbiota transplantation, bacteriophage therapy, and Clustered Regularly Interspersed Short Palindromic Repeats—CRISPR-associated protein systems along with dietary interventions have been assessed for their potential to restore microbial balance and reduce MDRO carriage. While promising results have emerged from early studies and animal models, most interventions remain investigational. Rigorous clinical trials, standardized protocols, and safety assessments are essential before these approaches can be integrated into routine practice for MDRO management.

Keywords: Antimicrobial resistance; Fecal microbiota transplantation; Gut decolonisation; Multidrug-resistant organisms; Selective digestive decontamination

Core Tip: Asymptomatic colonization of the gastrointestinal tract by extended-spectrum β-lactamase or carbapenamase-producing enterobacterales poses a substantial risk of infections caused by these resistant bacteria. Furthermore, this colonization carries a significant risk of transmitting these organisms to other patients and the broader community. Emerging interventions such as faecal microbiota transplantation, phage therapy, engineered probiotics, and Clustered Regularly Interspersed Short Palindromic Repeats—CRISPR-associated protein systems offer new hope for precise and sustainable decolonization. Additionally, dietary interventions and immune modulation may serve as supportive strategies to enhance the resilience of the host microbiota. However, many of these approaches are still in the nascent stage, and their long-term efficacy, safety, and regulatory approval remain barriers to routine clinical application.