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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 4 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.

Through the years, the individual microbes that reside in the human gastrointestinal (GI) tract have been labeled as pathogens, commensals, uncultivable, or unidentifiable. While exploration of particular species in the discovery and diagnosis of disease remains paramount, it is the landscape of the microbial community that continues to offer greater clues to the role of microbes in human health and quality of life. In contrast to other body systems, the human GI microbiome is ecologically diverse and complex and plays an active role in digestion, metabolism, behavior, heart size, and the development of the mucosal immune system, among other associations (1, 2). The composition of the gut microbiota is influenced by diet, age, host genetics, antibiotic treatment, and the environment (e.g., psychological stress, hygiene, climate, and allergies) (3). The microbial communities found in the gut have also been shown to contribute, both negatively and positively, not only to health issues rooted in the GI tract, but also to those of the respiratory and central nervous systems. An imbalance or shift of the gut microbiome has been linked to the development of a variety of disorders including inflammatory bowel disease (4–6), gastric ulcers and cancer (7–10), autism spectrum disorder (11–15), and obesity and diabetes (16–19). Because of the implications related to these changes and the development of “unhealthy” microbiomes, research is ongoing to continue to refine the definition and composition of a “healthy” gut microbiome.