Background: The gut microbiota of breast-fed infants is dominated by infant-type human-residential bifidobacteria (HRB) that contribute to infant health; thus, it is crucial to develop infant formulas that promote the establishment of a gut microbiota enriched with infant-type HRB, closely resembling that of breastfed infants. Methods: We compared various non-digestible prebiotic oligosaccharides and their combinations using a fecal culture system to explore which candidates could promote the growth of all infant-type HRB and rarely yield non-responders. The analysis included lactulose (LAC), raffinose (RAF), galactooligosaccharides (GOS), and short- and long-chain fructooligosaccharides. Fecal samples were collected from seven infants aged 1.5–10.2 months and cultured with each oligosaccharide individually or their combinations. Results: No single oligosaccharide effectively promoted the growth of all infant-type HRB, although GOS promoted the growth of HRB other than Bifidobacterium longum subsp. longum. Only the LAC/RAF/GOS group evenly and effectively promoted the growth of all infant-type HRB. Accordingly, acetate production was higher in fecal cultures supplemented with GOS or LAC/RAF/GOS than in the other cultures, suggesting that it is a superior combination for all infant-type HRB and rarely yields non-responders. Conclusions: This study can aid in developing infant formulas that help align the gut microbiota of formula-fed infants with that of breastfed infants.

Background/objectives: Human milk oligosaccharides (HMOs) are the third most abundant solid component of human milk. HMOs are selectively utilized by infant-type human-residential bifidobacteria (HRB), resulting in the formation of a gut microbiota dominated by bifidobacteria and the production of health-beneficial metabolites, such as acetate and aromatic lactic acids (ALAs), in breastfed infants. HMOs play key roles in infant health by acting as prebiotics, preventing infections, and regulating the immune system. However, the prevalence of HMO-utilizing bifidobacteria in the gut microbiota of infants and young children varies greatly between countries and regions, with some infants and children containing none. Methods: We used a pH-controlled single-batch fermenter to model the human gut microbiota and evaluated whether HMOs provide infants or young children having or lacking bifidobacteria with HMO-utilizing ability with any physiological benefits. We conducted fecal fermentation with 2’-fucosyllactose (2’-FL), with or without supplementation with a probiotic HRB strain ( Bifidobacterium longum subsp. infantis M-63). Results: 2’-FL alone did not significantly increase the relative abundance of bifidobacteria or the production of acetate and ALAs during fecal fermentation of infants and young children. Conversely, 2’-FL + M-63 significantly increased bifidobacteria and promoted acetate and ALA production in the fecal fermentation of both infants and young children. Conclusion: Health benefits from 2’-FL may be restricted by inter-individual and age-dependent differences in gut microbiota response. Supplementation with a probiotic HRB with high HMO-utilizing ability could overcome this restriction. Our findings provide insights into the development of formulas for infants and young children.