Donor-recipient specificity and age-dependency in fecal microbiota therapy and probiotic resolution of gastrointestinal symptoms

Fecal microbiota transplantation (FMT) has proven to be an effective treatment for recurrent Clostridioides difficile infection (rCDI) in both adult and pediatric patients. However, as microbiome development is a critical factor in children, it remains unclear whether adult fecal donors can provide age-appropriate functional restoration in pediatric patients. To address this issue, we conducted an integrated systems approach and found that concordant donor strain engraftment, along with metabolite restoration, are associated with FMT outcomes in both adult and pediatric rCDI patients. Although functional restoration after FMT is not strain-specific, specialized metabolic functions are retained in pediatric patients when adult fecal donors are used. Furthermore, we demonstrated broad utility of high-resolution variant-calling by linking probiotic-strain engraftment with improved gastrointestinal symptoms in adults with irritable bowel syndrome and in children with autism spectrum disorder. Our findings emphasize the importance of strain-level identification when assessing the efficacy of probiotics and microbiota-based therapeutics.

Automated summary

Fecal microbiota transplantation (FMT) is effective for treating rCDI in both adults and children. It is still uncertain whether adult fecal donors can provide age-appropriate restoration in pediatric patients due to the critical role of microbiome development in children. This study found that concordant donor strain engraftment and metabolite restoration are associated with FMT outcomes in both adult and pediatric rCDI patients. Additionally, high-resolution variant-calling linked probiotic-strain engraftment with improved gastrointestinal symptoms in adults with irritable bowel syndrome and children with autism spectrum disorder. These findings highlight the importance of strain-level identification when assessing the efficacy of probiotics and microbiota-based therapeutics.