| Summary: | Though antibiotics are the mainstay treatment for <i>Clostridioides difficile</i>, a large population of individuals infected will experience recurrence. In turn, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent <i>C. difficile</i> infection (rCDI). Mechanistically, by providing a healthy, diverse flora to the infected individual, FMT “resets” the underlying gut microbiome dysbiosis associated with rCDI. A proposed mechanism through which this occurs is via microbiome metabolites such as short-chain fatty acids (SCFAs); however, this has not been previously studied in pediatric patients. Using mass spectroscopy, we quantified pre- and post-transplant levels of acetate, isovalerate, butyrate, formate, and propionate in pediatric patients diagnosed with rCDI (<i>n</i> = 9). We compared pre- and post-transplant levels within the rCDI cohort at 1, 3, 6, and 12 months post-transplant and correlated these levels with healthy controls (<i>n</i> = 19). We witnessed a significant difference in the combined SCFA levels and the individual levels of acetate, butyrate, isovalerate, and propionate in the pre-treatment rCDI cohort compared to the healthy controls. In addition, there was a significant increase in combined SCFA levels at 12 months post-transplant within the rCDI group compared to that of their pre-transplant levels, and, more specifically, acetate, propionate, and isovalerate increased from pre-transplant to 12 months post-transplant. The longitudinal aspect of this study allowed us to identify mechanisms that contribute to the durability of responses to FMT, as well as characterize the unique patterns of short-chain fatty acid level recovery in rCDI pediatric patients.
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