Can FMT Be Used to Overcome Antibiotic-Resistant Strains?

Speaker: Michael Woodworth, United States

Introduction

In the session, the speaker highlighted the clinical and microbial influence of faecal microbiota transplantation (FMT) in tackling antibiotic-resistant organism (ARO) colonization, particularly in immunocompromised individuals such as kidney transplant recipients. The mechanisms of colonization resistance, microbial metabolite function, and genomic strain dynamics were also discussed.

Key Insights

Mechanisms of Colonization Resistance

• The important role of intestinal microbiota in health maintenance was highlighted, mainly via colonization resistance—involving short-chain fatty acid production, conversion of primary to secondary bile acid microbial metabolites, nutrient competition, and bacteriocin production—which inhibit pathogen growth.

Microbiota Diversity and Resistance

• An observational study involving liver transplant recipients and healthy controls showed that greater intestinal alpha diversity closely correlated with increased levels of short-chain fatty acids and secondary bile acids. Metabolic profiling alone, without sequencing, was found to be effective in predicting microbial diversity and infection risk, which could serve as a promising non-invasive biomarker.

FMT’s Potential for Antibiotic Resistance

• Various studies have demonstrated that FMT can lower antimicrobial resistance genes, reduce colonization of pathogens, and reduce the incidence of Clostridioides difficile infection, including urinary tract and bloodstream infections. Some data has suggested that it also reduces overall death at ninety days.  

The PREMIX trial

• The PREMIX trial, a randomized controlled study, evaluated the impact of FMT in kidney transplant recipients colonized with multidrug-resistant organisms (MDROs). The participants were categorized into either immediate FMT post bowel preparation or delayed FMT following observation.
• The FMT-first group experienced faster MDRO decolonization across extended spectrum β-lactamases (ESBL), vancomycin-resistant Enterococci (VRE), Carbapenem-resistant Enterobacteriaceae (CRE), and multidrug-resistant (MDR) Pseudomonas strains. They also had an 80% overall lower decolonization rate and reduced recurrence of MDRO infections.

Metagenomic and Strain-Level Analysis

• Strain replacement dynamics were observed post-FMT. In one participant, a resistant ESBL E. coli strain was replaced by a more susceptible one after FMT. Genomic and metagenomic analyses revealed both strains were present prior to FMT, suggesting FMT induced selection pressure. This stain-switching occurrence was observed in several participants, including those with Klebsiella pneumonia.  
• The review of the annotated genes indicated differential fitness features such as colicins, fimbrial proteins, membrane transporters, and surface receptors.
• Strain replacement was confirmed through in vitro assays demonstrating competitive inhibition between baseline and replacing E. coli or Klebsiella strains. Not all cases showed inhibition zones, suggesting variation in competitive mechanisms.
• Analysis of metagenomic datasets of healthy individuals validated that strain turnover may be a natural marker of microbial communities.

Clinical Implications

FMT has been demonstrated to be clinically effective and biologically active in modifying microbial colonization patterns, lowering infection recurrence, and enhancing colonization resistance. The detection of microbial and metabolite biomarkers holds promise for non-sequencing-based diagnostics. The in vitro strain competition highlights FMT’s potential in promoting favorable microbial shifts.

FMT for The Treatment of Metabolic Syndrome and Fatty Liver

Speaker: Tiphaine Le Roy, France                              

Introduction

The potential of fecal microbiota transplantation (FMT) for metabolic disorders was discussed, with a focus on basic aspects. The speaker discussed the origins of this link from an early animal study, where germ-free mice were found to have lower fat mass and improved metabolic markers than those raised conventionally. Subsequent work also showed that obese individuals may transfer obesity-related traits, establishing a causal association between gut microbiota and metabolic health.

Evidence for FMT in Adult Metabolic Disorders

Glucose Metabolism and Adiposity

• In adults with metabolic syndrome, lean donor FMT demonstrated improved peripheral insulin sensitivity, but the effects were not sustained beyond 18 weeks and exhibited high variability.
• Studies have also found minimal benefits only when FMT was combined with low-fermentable fiber.
• FMT alone has not shown any consistent effects in improving BMI or adiposity.

Blood Lipids and Cardiovascular Parameters

• Inconsistent results have been noted regarding FMT’s influence on lipid profiles. Few studies have reported modest improvements in cholesterol and triglyceride levels following lean donor FMT, while others found substantial benefits in control groups.
• In a study, microbiota from post-bariatric surgery showed potential but lacked statistical significance. FMT combined with lifestyle changes was found to be effective in improving lipid profiles.

Key Considerations for FMT Efficacy

Donor Microbiota Engraftment Challenges

• In metabolic disorders, long-term restoration of a symbiotic microbial ecosystem is needed, making engraftment more complex than in infectious conditions. Several studies have reported poor engraftment rates due to recipient gut environment, host-secreted immunoglobulins, nutrient influx and availability, metabolic alterations and diet.
• A case was presented where autologous FMT following a green Mediterranean diet aided in sustained weight loss.

Importance of Critical Time Window for FMT Efficacy

• Animal studies have suggested that a time window is critical for the efficacy of FMT. A mouse study demonstrated that germ-free mice colonized with wild mouse microbiota at birth were entirely resistant to diet-induced obesity.
• This benefit of metabolic programming was seen within the first two weeks of life in mice, but not after this period.
• A similar time window in humans is unknown, but this finding emphasized the concept of the Developmental Origins of Health and Disease, which may guide human interventions in the future.

Clinical Implications

FMT’s role in metabolic syndrome and obesity appears to be limited, with minimal benefits on glucose control and lipid profiles. FMT’s efficacy could be improved with co-interventions such as diet and strategic timing.   

ESPID, May 26-30 2025, Bucharest, Romania