Cross-kingdom microbial associations characterize responsiveness to fecal microbiota transplantation in patients with irritable bowel syndrome.

BACKGROUND

Precise outcome prediction for fecal microbiota transplantation (FMT) in irritable bowel syndrome (IBS) remains a clinical challenge. The roles of the gut virome and its interplay with bacteria in FMT efficacy are particularly underexplored. This secondary analysis aimed to conduct an exploratory, hypothesis-generating investigation into these cross-kingdom dynamics.

METHODS

We conducted a secondary, integrative analysis of a published cohort, performing longitudinal, cross-kingdom metagenomic profiling on 83 samples from 22 IBS patients and healthy donors. We integrative approach combined microbial diversity, species-specific biomarker identification, bacterial-viral associated networks, and exploratory random forest modeling to identify microbial features associated with FMT outcomes.

RESULTS

IBS patients showed higher bacterial and viral alpha diversity than donors. Cross-kingdom profiling identified 223 bacterial and 724 viral biomarkers. Donor-enriched biomarkers were predominantly health-associated Bacteroidetes (e.g., B. ovatus, B. faecis), whereas pre-FMT-enriched biomarkers were largely Firmicutes (e.g., B. obeum) with potential pathobiont roles. The Effect and No effect groups displayed different microbial trajectories. Although both groups shifted toward a donor-like composition initially, only responders maintained a stable donor-like ecology throughout the 12-month follow-up, supported by more resilient bacterial-viral association networks. Exploratory random forest modeling highlighted microbial features, such as R. pickettii, with high relative importance for outcome discrimination. However, permutation testing (p = 0.548-0.616) confirmed that model performance on this small cohort did not exceed chance level, underscoring the risk of overfitting and the exploratory nature of these computational findings.

CONCLUSIONS

This integrative re-analysis provides preliminary evidence that cross-kingdom gut microbiome profiles are strongly associated with FMT outcomes in IBS. Successful outcomes appear linked to sustained donor-like remodeling and stable bacterial-viral networks. Our findings are primarily hypothesis-generating and offer a framework of candidate biomarkers for future validation in larger cohorts. This work underscores the necessity of external validation to develop robust, microbiome-based tools for personalized FMT therapy.