A single session of FMT did not significantly enhance MDRO decolonization or decrease AMR genes in patients with GI diseases, though it modulated gut microbiome diversity and composition.
Key Findings
Results
FMT did not significantly improve MDRO decolonization rates compared to sham intervention at 4 weeks.
Decolonization occurred in 18 patients (31.0%) in the FMT group versus 17 patients (30.4%) in the sham group
Absolute difference was 0.6% (95% CI, -16.2% to 17.6%); P = .94
Analysis was intention-to-treat with 114 randomized patients
Five patients (2 FMT, 3 sham) were lost to follow-up
Results
FMT did not significantly reduce antimicrobial resistance (AMR) gene burden compared to sham at 4 weeks.
Median (IQR) AMR genes were 2.5 (1.2 to 3.0) in the FMT group versus 2.0 (1.0 to 3.0) in the sham group
P = .68, indicating no statistically significant difference
Reduction in AMR genes was a co-primary outcome alongside MDRO decolonization rate
Methods
The study population was predominantly colonized with carbapenem-resistant Enterobacteriaceae (CRE) or extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) at baseline.
55 patients (94.8%) in the FMT group and 56 patients (100%) in the sham group had CRE or ESBL-producing Enterobacteriaceae
Mean (SD) age was 40.6 (12.5) years; 80 (70.2%) were male
52 patients (45.6%) had pancreatitis, 43 (37.7%) had cirrhosis, and 19 (16.7%) had other GI disorders
Recruitment occurred from July 2022 to June 2024 at a tertiary care center in India
Results
FMT resulted in enrichment of short-chain fatty acid (SCFA)-producing bacteria in the gut microbiome, an effect not observed in the sham group.
Among 71 patients who underwent 16S ribosomal RNA gene sequencing at 4 to 6 weeks after 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
FMT modulated gut microbiome diversity and composition despite failing to achieve decolonization
Results
FMT induced only modest, transient alterations in the gut mycobiome.
Mycobiome analysis used ITS2 sequencing
Alterations in fungal composition following FMT were described as 'modest' and 'transient'
This contrasts with the more durable bacterial microbiome changes observed
Results
Viral diversity in the gut remained unchanged after FMT.
Virome analysis was conducted using virus-like particles shotgun sequencing
Viral diversity remained unchanged after FMT
Virome composition was a secondary outcome of the study
Results
Adverse events were comparable between the FMT and sham intervention groups.
No significant difference in adverse events was reported between the two groups within 4 weeks
FMT was delivered via colonoscopy; sham intervention was delivered via sigmoidoscopy with saline injection
Adverse events and incidence of MDRO infections were prespecified secondary outcomes
What This Means
This research suggests that a single session of fecal microbiota transplant (FMT) — a procedure where stool from a healthy donor is transferred into a patient's gut — did not help patients with gastrointestinal diseases get rid of dangerous drug-resistant bacteria (called multidrug-resistant organisms, or MDROs) any better than a fake procedure using saline. The trial enrolled 114 patients in India, most of whom had pancreatitis or cirrhosis, and about a third of patients in both the FMT and sham groups cleared their drug-resistant bacteria after four weeks, with no meaningful difference between them. The genetic markers of antibiotic resistance in the gut were also similarly unchanged in both groups.
Despite failing to clear the drug-resistant bacteria, FMT did produce some changes in the gut's microbial ecosystem. Patients who received FMT showed increases in bacteria that produce short-chain fatty acids, which are generally considered beneficial for gut health. However, the fungal community (mycobiome) showed only small and temporary changes after FMT, and the viral community (virome) was essentially unaffected. Safety was comparable between the two groups.
This research suggests that while FMT can shift the overall bacterial landscape of the gut, a single colonoscopy-based FMT session is not sufficient to reliably eliminate drug-resistant bacteria in hospitalized patients with serious gastrointestinal diseases. This is an important finding given the growing global problem of antibiotic resistance and the lack of approved treatments for gut colonization by these dangerous organisms. Future research may need to explore repeated FMT sessions, different delivery methods, or different patient populations to determine whether FMT could play a role in combating antibiotic-resistant gut colonization.