Precision modulation of dysbiotic adult microbiomes with a human-milk-derived synbiotic reshapes gut microbial composition and metabolites

Manipulation of the gut microbiome using live biotherapeutic products shows promise for clinical applications but remains challenging to achieve. Here, we induced dysbiosis in 56 healthy volunteers using antibiotics to test a synbiotic comprising the infant gut microbe, Bifidobacterium longum subspecies infantis (B. infantis), and human milk oligosaccharides (HMOs). B. infantis engrafted in 76% of subjects in an HMO-dependent manner, reaching a relative abundance of up to 81%. Changes in microbiome composition and gut metabolites reflect altered recovery of engrafted subjects compared with controls. Engraftment associates with increases in lactate-consuming Veillonella, faster acetate recovery, and changes in indolelactate and p-cresol sulfate, metabolites that impact host inflammatory status. Furthermore, Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts lactate produced by B. infantis to propionate, an important mediator of host physiology. These results suggest that the synbiotic reproducibly and predictably modulates recovery of a dysbiotic microbiome. [Display omitted] •B. infantis engrafts into an antibiotic-perturbed adult human gut microbiome•HMOs support engraftment of B. infantis in adults at up to 81% relative abundance•Microbiome structure and gut metabolite levels were altered in engrafted adults•B. infantis cross-fed Veillonella in adult patients, mouse models, and in vitro Button et al. demonstrate precision microbiome engineering through human-milk-oligosaccharide-fed Bifidobacterium longum subspecies infantis in adult, antibiotic-perturbed gut microbiomes. Engraftment in adult subjects leads to reproducible changes in the microbiome, including cross-feeding of propionate-producing Veillonella spp. Reproducible positive impacts on an array of microbial metabolites point to therapeutic potential.