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The purpose of our experiment was to explore how stochastic inter-individual variation in the mammalian gut microbiome may link to inflammatory bowel disease (IBD) susceptibility, and guide the development of a perinatal preventative probiotic. Dextran sodium sulfate (DSS) was introduced to C57BL/6J mice to induce acute colitis as a model of IBD. Potentially protective bacteria were identified using a discovery-validation cohort approach towards stochastic DSS susceptibility. Lactobacilli (two different cocktails of L. reuteri and L. johnsonii strains) or control media were supplemented by mouth to dams prior to delivery and during lactation (i.e. perinatal probiotic). The pups were evaluated for DSS susceptibility at young adulthood. Fecal Lactobacillus was increased in the DSS-resistant mice in both the discovery and validation cohorts. Maternal supplementation of female offspring with an L. reuteri cocktail (strains 6798-1, 6798-jm, and 6798-cm) induced progressive microbiome separation and protection against colitis by young adulthood. Maternal supplementation of L. reuteri could confer protection against DSS colitis in young adult female mice. This work is the first to exploit stochastic mammalian microbiome variation to guide microbial therapeutic identification. Our findings underscore neonatal microbiome plasticity and set the stage for the potential development of perinatally deliverable protective probiotics against human IBD.

Background & Aims Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI. Methods We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMT at 18 pediatric centers, from February 1, 2004, to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT. Results Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations. Conclusions Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.