The Impact of Age on Microbiome Diversity and Engraftment of Fecal Microbiota Spores, Live (FMS) in Patients With Recurrent Clostridioides difficile Infection

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Conference Proceeding

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American Journal of Gastroenterology


Introduction: Patients (pts) .65 yr of age have a higher risk of recurrent Clostridioides difficile infection (rCDI) than younger pts, possibly due to poor microbiome resilience after antibiotic discontinuation. In a post hoc analysis of 2 Phase 3 trials in adults with rCDI (ECOSPOR III and ECOSPOR IV), we analyzed effects of age on compositional/functional microbiome changes after treatment with fecal microbiota spores, live (FMS; formerly SER-109), an FDA-approved, oral, microbiota-based therapeutic comprised of Firmicutes spores given after standard-of-care antibiotics. Methods: Stool samples were obtained from pts with rCDI following symptom resolution after antibiotics at baseline (pre-dose) and Week 1 post-treatment in the randomized, controlled ECOSPOR III trial and open-label ECOSPOR IV trial. Microbiome profiles were generated from whole metagenomic sequencing data using MetaPhlAn2. Microbiome diversity was reported with Shannon diversity, and engraftment was defined as newly appearing dose species from baseline (before FMS). Concentrations of secondary bile acid (2°BA), which inhibit vegetative C. difficile bacterial growth, were measured via targeted LC–MS panel. Subgroup differences (age, , 65 vs $65 yr) were analyzed with linear mixed models. Data from the placebo arm are included in the figures as a reference, but not included in the statistical models. Results: A total of 362 baseline and 249 Week 1 stool samples were available for analysis. . At baseline, Shannon diversity was not significantly different between age groups and increased at Week 1; similar increases in diversity were observed (Figure 1A). Engraftment magnitude after FMS was comparable between subgroups (Figure 1B). Baseline 2°BA concentrations were comparably low in age groups in ECOSPOR III; 2°BA concentrations were significantly lower in ECOSPOR IV in those $65 yr (Figure 1C). Concentrations of 2°BA were comparable between subgroups 1 week after FMS. Consistent with these compositional/metabolic changes, of 349 FMS-treated pts in ECOSPOR III or ECOSPOR IV, rCDI rates at Week 8 were low in both age groups (, 65 yr, 4.2% [95% CI, 1.7-8.5]; $65 yr, 14.2% [95% CI, 9.5- 20.1]), while placebo rates in ECOSPOR III were 30.8% and 46.3% in pts , 65 and $65 yr, respectively. Conclusion: Pts in both age groups responded similarly, suggesting treatment with the oral microbiome therapeutic, FMS, may be beneficial in early restoration of microbiome diversity/function, regardless of age.





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American College of Gastroenterology Annual Scientific Meeting, October 20-25, 2023, Vancouver, Canada

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