AUTHOR=Özcan Ezgi , Sela David A. 

TITLE=Inefficient Metabolism of the Human Milk Oligosaccharides Lacto-N-tetraose and Lacto-N-neotetraose Shifts Bifidobacterium longum subsp. infantis Physiology

JOURNAL=Frontiers in Nutrition

VOLUME=5

YEAR=2018

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2018.00046

DOI=10.3389/fnut.2018.00046

ISSN=2296-861X

ABSTRACT=<p>Human milk contains a high concentration of indigestible oligosaccharides, which likely mediated the coevolution of the nursing infant with its gut microbiome. Specifically, <italic>Bifidobacterium longum</italic> subsp. <italic>infantis</italic> (<italic>B. infantis</italic>) often colonizes the infant gut and utilizes these human milk oligosaccharides (HMOs) to enrich their abundance. In this study, the physiology and mechanisms underlying <italic>B. infantis</italic> utilization of two HMO isomers lacto-<italic>N</italic>-tetraose (LNT) and lacto-<italic>N</italic>-neotetraose (LNnT) was investigated in addition to their carbohydrate constituents. Both LNT and LNnT utilization induced a significant shift in the ratio of secreted acetate to lactate (1.7–2.0) in contrast to the catabolism of their component carbohydrates (~1.5). Inefficient metabolism of LNnT prompts <italic>B. infantis</italic> to shunt carbon toward formic acid and ethanol secretion. The global transcriptome presents genomic features differentially expressed to catabolize these two HMO species that vary by a single glycosidic linkage. Furthermore, a measure of strain-level variation exists between <italic>B. infantis</italic> isolates. Regardless of strain, inefficient HMO metabolism induces the metabolic shift toward formic acid and ethanol production. Furthermore, bifidobacterial metabolites reduced LPS-induced inflammation in a cell culture model. Thus, differential metabolism of milk glycans potentially drives the emergent physiology of host-microbial interactions to impact infant health.</p>