Fecal Microbiota Transplantation Commonly Failed in Children With Co-Morbidities

Abstract

Objectives: Fecal microbiota transplantation (FMT) is arguably the most effective treatment for recurrent Clostridioides difficile infection (rCDI). Clinical reports on pediatric FMT have not systematically evaluated microbiome restoration in patients with co-morbidities. Here, we determined whether FMT recipient age and underlying co-morbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources.

Methods: Eighteen rCDI patients participating in a single-center, open-label prospective cohort study received fecal preparation from a self-designated (single case) or two universal donors. Twelve age-matched healthy children and four pediatric ulcerative colitis (UC) cases from an independent serial FMT trial, but with a shared fecal donor were examined as controls for microbiome restoration using 16S rRNA gene sequencing of longitudinal fecal specimens.

Results: FMT was significantly more effective in rCDI recipients without underlying chronic co-morbidities where fecal microbiome composition in post-transplant responders was restored to levels of healthy children. Microbiome reconstitution was not associated with symptomatic resolution in some rCDI patients who had co-morbidities. Significant elevation in Bacteroidaceae, Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, and Erysipelotrichaceae was consistently observed in pediatric rCDI responders, while Enterobacteriaceae decreased, correlating with augmented complex carbohydrate degradation capacity.

Conclusion: Recipient background disease was a significant risk factor influencing FMT outcomes. Special attention should be taken when considering FMT for pediatric rCDI patients with underlying co-morbidities.

Figure 1.. FMT promotes the reconstitution of microbiome composition and function, and alpha-diversity in rCDI responders.

(A) Shannon index of pediatric CDI and UC patients receiving identical donor material. (B) Beta-diversity analysis of microbiome composition (ASVs) and predicted function (PICRUSt2) using Bray-Curtis dissimilarity metric. Significance denotations: n.s., not significant; *, p < 0.05; ***, p < 0.001.

Figure 2.. Successful microbiome reconstitution is highly conserved but age-dependent in pediatric rCDI recipients.

(A) Hierarchical clustering of family abundance highlights the reconstitution of conserved microbiome (box with dashed line) in pediatric rCDI responders. Notably, CDI-P3 (PreFMT) clustered with healthy controls suggesting potential C. difficile colonization rather than active infection. (B) Responder microbiomes of pediatric rCDI patients were similar to pediatric healthy controls. Bifidobacteriaceae expansion is a pediatric-specific microbiome feature in PostFMT samples when compared to adult donor microbiomes. Significance denotations: *, p < 0.05; **, p < 0.01; ***, p < 0.001.

Figure 3.. Decolonization of Enterobacteriaceae is associated with carbohydrate utilization of healthy dominant commensals engrafted in rCDI responders.

(A) ASV-ASV correlation network analysis highlights the strong negative correlation of four Enterobacteriaceae with healthy microbiota. (B) Four ASVs with diverse genera represented a major contributor of the Enterobacteriaceae abundance in pre-FMT specimens. (C) Enterobacteriaceae is negatively correlated (p < 0.001) with complex carbohydrate degradation of healthy microbiomes.