The role of the gut microbiome in multidrug-resistant organism colonization and infection

Colonization of the gastrointestinal tract by multidrug-resistant organisms (MDROs) is a precursor to endogenous infection and onward transmission. The gut microbiome provides colonization resistance (CR)-the ability to prevent or limit the establishment of pathogens, including MDROs-through nutrient and niche competition, production of inhibitory metabolites, and immune modulation. However, its integrity is threatened by antibiotics, adverse diet, and healthcare exposures.

To describe mechanistic, epidemiological, and interventional evidence on the role of the gut microbiome in MDRO colonization and infection, and to highlight implications for clinical practice, policy, and research.

PubMed/MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from 1 January 2000 to 30 September 2025, supplemented by hand-searching of key international guidelines (EUCIC/ESCMID, WHO, CDC/ECDC, NICE/UKHSA) and reference lists.

CR is shaped by microbial and host factors, including metabolic interactions, immune responses, and environmental exposures. Antimicrobials, nonantimicrobial drugs, diet, travel, and healthcare contact can disrupt the microbiota, predisposing to MDRO acquisition and infection. Observational data link gut microbial composition to risk of colonization and infection outcomes, but predictive models are imperfect. Interventions to preserve or restore CR-such as diet-based strategies, probiotics, and faecal microbiota transplant-show promise but require robust and repeated, context-specific evaluation.

Protecting the microbiome must be a clinical and policy priority. Short-course, microbiome-sparing antimicrobial regimens, microbiome-aware diagnostics, and public health measures that support microbiome resilience could reduce MDRO burden and infections. Rigorous trials of microbiota-based therapies and integration of microbiome stewardship into antimicrobial resistance strategies are essential for translating mechanistic insights into patient benefit.