Gut microbiota differs between treatment outcomes early after fecal microbiota transplantation against recurrent Clostridioides difficile infection

Abstarct In fecal microbiota transplantation (FMT) against recurrent Clostridioides difficile infection (CDI), clinical outcomes are usually determined after 8 weeks. We hypothesized that the intestinal microbiota changes earlier than this timepoint, and analyzed fecal samples obtained 1 week after treatment from 64 patients diagnosed with recurrent CDI and included in a randomized clinical trial, where the infection was treated with either vancomycin-preceded FMT (N = 24), vancomycin (N = 16) or fidaxomicin (N = 24). In comparison with non-responders, patients with sustained resolution after FMT had increased microbial alpha diversity, enrichment of Ruminococcaceae and Lachnospiraceae, depletion of Enterobacteriaceae, more pronounced donor microbiota engraftment, and resolution of gut microbiota dysbiosis. We found that a constructed index, based on markers for the identified genera Escherichia and Blautia, successfully predicted clinical outcomes at Week 8, which exemplifies a way to utilize clinically feasible methods to predict treatment failure. Microbiota changes were restricted to patients who received FMT rather than antibiotic monotherapy, indicating that FMT confers treatment response in a different way than antibiotics. We suggest that early identification of microbial community structures after FMT is of clinical value to predict response to the treatment.

Automated summary

This study aimed to explore the relationship between early changes in the intestinal microbiota and clinical outcomes following fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI). The results showed that patients with sustained resolution after FMT had different microbial diversity, abundance, and gut microbiota dysbiosis compared to non-responders. Additionally, a constructed index based on clinically feasible methods successfully predicted treatment failure. It was also found that FMT had a more pronounced impact on the gut microbiota compared to antibiotic monotherapy. Therefore, early identification of microbial community structures after FMT is clinically valuable for predicting treatment response.