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Background <p>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.</p> Methods <p>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.</p> Results <p>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 <i>Bacteroidetes</i> (e.g., <i>B. ovatus</i>, <i>B. faecis</i>), whereas pre-FMT–enriched biomarkers were largely <i>Firmicutes</i> (e.g., <i>B. obeum</i>) with potential pathobiont roles. The <i>Effect</i> and <i>No effect</i> 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 <i>R. pickettii</i>, with high relative importance for outcome discrimination. However, permutation testing (<i>p</i> = 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Qiulong Yan,
  • Min Li,
  • Guangyang Wang,
  • Aiqin Zhang,
  • Yuming Li,
  • Ruochun Guo,
  • Yue Zhang,
  • Wei Yang,
  • Yidi Zhang,
  • Xiaohua Liu,
  • Xin Li,
  • Ning Zheng,
  • Leyi Wang,
  • Shao Fan,
  • Renzhen Ma,
  • Tong Lu,
  • Shan Zhou,
  • Tianyu Guan,
  • Guorui Xing,
  • Shenghui Li,
  • Liang Wang,
  • Yanxia Li

摘要

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.