Fecal microbiota transplantation commonly failed in children with co-morbidities

Authors: KELLERMAYER, RICHARD - Baylor College Of Medicine; WU, QINGLONG - Baylor College Of Medicine; NAGY-SZAKAL, DOROTTYA - Baylor College Of Medicine; QUELIZA, KAREN - Baylor College Of Medicine; IHEKWEAZU, FAITH - Baylor College Of Medicine; BOCCHINI, CLAIRE - Baylor College Of Medicine; MAGEE, ABRIA - Baylor College Of Medicine; OEZGUEN, NUMAN - Texas Children'S Hospital; SPINLER, JENNIFER - Texas Children'S Hospital; HOLLISTER, EMILY - Texas Children'S Hospital; SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC); VERSALOVIC, JAMES - Texas Children'S Hospital; LUNA, RUTH ANN - Baylor College Of Medicine; SAVIDGE, TOR - Baylor College Of Medicine

Submitted to: Journal of Pediatric Gastroenterology and Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/26/2021
Publication Date: 2/1/2022
Citation: Kellermayer, R., Wu, Q., Nagy-Szakal, D., Queliza, K., Ihekweazu, F.D., Bocchini, C.E., Magee, A.R., Oezguen, N., Spinler, J.K., Hollister, E.B., Shulman, R.J., Versalovic, J., Luna, R., Savidge, T.C. 2022. Fecal microbiota transplantation commonly failed in children with co-morbidities. Journal of Pediatric Gastroenterology and Nutrition. 74(2):227-235. https://doi.org/10.1097/MPG.0000000000003336.
DOI: https://doi.org/10.1097/MPG.0000000000003336

Interpretive Summary: Clostridioides difficile infection of the intestine is common and can be associated with serious illness or even death. Recently, it has been shown that in cases where traditional antibiotic treatment fails, transplantation of gut bacteria from healthy individuals to those with the infection can be effective. In this study, we found that children who had other medical problems besides the Clostridioides difficile infection were less likely to respond to the transplantation and be cured of the infection. This study provides fundamental research on gut bacteria and means to create a healthy microbiome.

Technical Abstract: 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 comorbidity influenced clinical outcomes and microbiome restoration when treated from shared fecal donor sources. 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. 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 comorbidities. 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. 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.