Dosing a synbiotic of human milk oligosaccharides and B. infantis leads to reversible engraftment in healthy adult microbiomes without antibiotics.

Predictable and sustainable engraftment of live biotherapeutic products into the human gut microbiome is being explored as a promising way to modulate the human gut microbiome. We utilize a synbiotic approach pairing the infant gut microbe Bifidobacterium longum subspecies infantis (B. infantis) and human milk oligosaccharides (HMO). B. infantis , which is typically absent in adults, engrafts into healthy adult microbiomes in an HMO-dependent manner at a relative abundance of up to 25% of the bacterial population without antibiotic pretreatment or adverse effects. Corresponding changes in metabolites are detected. Germ-free mice transplanted with dysbiotic human microbiomes also successfully engraft with B. infantis in an HMO-dependent manner, and the synbiotic augments butyrate levels both in this in vivo model and in in vitro cocultures of the synbiotic with specific Firmicutes species. Finally, the synbiotic inhibits the growth of enteropathogens in vitro. Our findings point to a potential safe mechanism for ameliorating dysbioses characteristic of numerous human diseases. [Display omitted] • Co-dosing with HMO enables reversible gut engraftment of B. infantis in healthy adults • The synbiotic is safe and does not require the use of antibiotics for gut engraftment • Synbiotic induces butyrate production in mice colonized with dysbiotic human microbiota • In vivo and in vitro models show beneficial impacts on metabolites and enteropathogens Button et al. present proof-of-concept data showing that Bifidobacterium infantis , an infant gut microbe, can be reversibly introduced and maintained in healthy adult guts without prior antibiotic treatment if human milk oligosaccharides are provided. Higher colonization levels are achieved in dysbiotic human-microbiota-associated mice with concomitant butyrate production, suggesting therapeutic potential. [ABSTRACT FROM AUTHOR]