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

Table 5 Summary of the methods for gut decolonization

Method	Mechanism/strategy	Current status/potential	Limitations
Synbiotics (Prebiotics + Probiotics)	Combination approach to feed beneficial bacteria and inhibit pathogen growth	Evidence for Clostridioides difficile; under evaluation for broader MDRO decolonization	Strain/pathogen-specific efficacy; low to moderate benefits only; inconsistent results across trials
Live biotherapeutic products	Consortia of beneficial bacteria designed to displace pathogens and modulate immunity	Examples include VE707; under investigation for MDROs	Mostly preclinical; unclear long-term effects; regulatory challenges for approval
Selective digestive decontamination	Use of non-absorbable oral and systemic antibiotics to decolonize gut MDROs	Used in ICU settings; variable evidence; some success in ESBL-E decolonization	Promotes resistance (e.g., colistin-resistant strains); disrupts microbiota; lacks standardized protocols
Fecal microbiota transplantation	May restore healthy microbiota to compete MDROs	Successful in small studies; ongoing trials for CRE, VRE. Requires standardization and safety screening	Risk of transferring ARGs; labor-intensive donor screening; cold-chain dependency
Bacteriophage therapy	Phages specifically target and lyse pathogenic strains without affecting commensals	Promising; several preclinical and early clinical studies underway. Challenges include phage resistance and regulatory issues	Narrow host range; potential phage resistance; immunogenicity; storage and regulatory hurdles
CRISPR-Cas system	Use of gene-editing tools to selectively target and eliminate resistance genes	Under experiment, promising specificity and minimal off-target effects	Delivery method challenges; early-stage development; ethical and safety concerns

MDRO: Multi-drug resistant organisms; ICU: Intensive care unit; ESBL: Extended spectrum beta-lactamases; CRE: Carbapenem resistant enterobacteriaceae; VRE: Vancomycin resistant enterococcus; ARG: Antibiotic resistant.