A unique blend of five human milk oligosaccharides supports recovery of infant microbiome composition and function after ex vivo antibiotic use

Human milk oligosaccharides (HMOs) are the third most abundant solid component of human breast milk, with well-established prebiotic and immunomodulatory functions. HMOs serve as selective substrates to support the growth of beneficial microbes in the developing gastrointestinal tract. At the same time individual HMOs have been shown to also exert selection against pathogens via direct anti-adhesive mechanisms. A longstanding hypothesis has held that HMOs act in concert and with other bioactive components of milk, and that this complex matrix of milk components collectively accounts for both the benefits to microbiome development and reduced risk of infectious disease associated with breastfeeding. The prebiotic activity of a diverse blend of fucosylated, acetylated, and sialylated HMOs was examined using microbiota cultured in an <i>ex vivo</i> model of the infant gastrointestinal tract before, during and after the supplementation of common childhood antibiotics. The anti-adhesive activity of this blend against infant-prevalent bacterial pathogens was tested using <i>in vitro</i> cultured intestinal epithelial cells. Taken together, this data suggests that a blend of 5 specific HMOs acts through multiple selection mechanisms to shape the development of the microbiota and interrupt opportunistic microbial pathogenesis.