Amino acid-based formula feeding is associated with increased risk of Clostridioides difficile-associated disease in children younger than two years.

Infants and toddlers were previously considered to be exempt from Clostridioides difficile-associated disease (CDAD). However, recent studies reported that Clostridioides difficile (C. difficile) infection can cause severe gastrointestinal symptoms within this age group, yet the influential risk factors related to CDAD in infants remain unknown. Here, we investigated 27 CDAD cases in infants and toddlers under two and found that the amino acid-based formula (AAF) feeding is a notable risk factor closely associated with the development of CDAD in infants. Infants fed with AAF exhibit reduced levels of Bifidobacteria, which were reported to compete with C. difficile, in their fecal microbiomes. Lastly, we found that mice transplanted with feces from AAF-fed infant donors, compared with those from normal formula (NF)-fed donors, were more susceptible to CDAD. These findings shed light on the understanding of variables influencing infant CDAD and offer valuable insights for its prevention.