Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized...

Gut colonization by multidrug-resistant organisms (MDROs) is a risk factor for infection with these pathogens. There are no approved therapeutic interventions to combat it.

To assess the efficacy of fecal microbiota transplant (FMT) in causing MDRO decolonization and decreasing antimicrobial resistance (AMR) genes and its impact on gut microbiome, virome, and mycobiome composition in patients with gastrointestinal (GI) diseases.

This randomized, double-blind, sham-controlled clinical trial was conducted in a gastroenterology ward and intensive care unit at a tertiary care center in India. Participants were patients with GI diseases with persistent MDRO colonization. Patient recruitment occurred from July 2022 to June 2024, with follow-up completed in July 2024. Data were analyzed from October 1, 2024, to April 25, 2025.

FMT via colonoscopy or sham intervention (sigmoidoscopy with saline injection).

Co-primary outcomes were MDRO decolonization rate and decrease in antimicrobial resistance genes (AMR) at 4 weeks after the intervention. Secondary outcomes included changes in stool microbiome (16S ribosomal RNA amplicon sequencing), virome (viruslike particles shotgun sequencing), and mycobiome (ITS2 sequencing); incidence of MDRO infections; and adverse events within 4 weeks.

Of 114 randomized patients (mean [SD] age, 40.6 [12.5] years; 80 [70.2%] male; 52 patients [45.6%] with pancreatitis; 43 patients [37.7%] with cirrhosis; 19 patients [16.7%] with other GI disorders), 58 received FMT and 56 received the sham intervention. Most patients were colonized with carbapenem-resistant Enterobacteriaceae or extended-spectrum β-lactamase-producing Enterobacteriaceae at baseline (55 patients [94.8%] in the FMT group and 56 patients [100%] in the sham group). Five patients (2 in the FMT group, 3 in the sham group) were lost to follow-up. Intention-to-treat analysis showed no significant differences in MDRO decolonization (18 patients [31.0%] in the FMT group vs 17 patients [30.4%] in the sham group; absolute difference, 0.6% [95% CI, -16.2% to 17.6%]; P = .94) or AMR genes (median [IQR], 2.5 [1.2 to 3.0] genes in the FMT group vs 2.0 [1.0 to 3.0] genes in the sham group; P = .68), with comparable adverse events. Among 71 patients who underwent 16S ribosomal RNA gene sequencing at 4 to 6 weeks after the intervention, enrichment of bacteria capable of producing short-chain fatty acids was observed in the FMT group. These microbial alterations were not observed in the sham group. However, viral diversity remained unchanged after FMT. Mycobiome analysis revealed that FMT induced only modest, transient alterations in the gut mycobiome.

This randomized clinical trial found that while a single session of FMT did not significantly enhance MDRO decolonization or decrease AMR genes in patients with GI diseases, it modulated gut microbiome diversity and composition.

Clinical Trials Registry-India Registration No. 2022/07/043847.