STUDENT TRAVEL AWARD RECIPIENT: Maternal FUT2 Polymorphisms Influence the Gut Microbial Communities of Breastfed Infants

Z. T. Lewis1,4, S. G. Totten2,4, J. Smilowitz3,4, D. G. Lemay5, K. M.
Kalanetra1,4, M. Ryazantseva1,4, J. B. German3,4, C. B. Lebrilla2,4, D. A. Mills1,3,4*

1Department of Viticulture and Enology, UC Davis, 2Department of Chemistry, UC Davis, 3Department of Food Science and Technology, UC Davis, 4Foods For Health Institute, UC Davis, 5Genome Center, UC Davis

Humans possess many enzymes responsible for the glycosylation of various substrates, and individuals vary in their functional repertoire of these glycosyl transferases. Inactive alleles of the fucosyltransferase 2 gene (FUT2; termed “secretor” due to its role in the expression of ABO blood types in secretions) are common in many populations. Several health-related effects of expressing only glycoforms lacking in 2’ fucosylation (as non-secretors do) have been shown, although the mechanism for these effects is not always clear. Select members of the genus Bifidobacterium (common infant gut commensals) are known to be able to consume 2’ fucosylated glycans, such as the oligosaccharides found in the breast milk of a secretor mother. These oligosaccharides are generally indigestible by the infant, and appear to have prebiotic action. Our hypothesis is that non-secretor mothers will enrich a different set of microbiota than secretor mothers by applying selective pressure to possess a consumption-enabling fucosidase. We sought to determine if infants fed by non-secretor mothers are under-colonized in bifidobacteria due to their lack of 2’ fucosylated glycans. We examined the fecal communities of a cohort of exclusively breast-fed infants using next-generation sequencing, Bifidobacterium-specific qPCR and a bifidobacteria-focused terminal restriction fragment length polymorphism analysis. Metadata collected included the mothers’ secretor genotype determined via FUT2 gene analysis and secretor phenotype determined by mass spectrometry on breast-milk samples. The microbiota data indicated that, on average, bifidobacteria are established in infants fed by secretor mothers earlier and more often than infants fed by non-secretor mothers. Moreover, infants lacking high levels of bifidobacteria in their feces were colonized by Escherichia and Streptococcus, bacterial genera considered less desirable than bifidobacteria. In secretor-fed infants percentages of the Bifidobacterium longum group were most strongly correlated with percentages of order Bifidobacteriales. However, in non-secretor-fed infants Bifidobacterium breve held this distinction, and the B. longum group was anti-correlated with levels of Bifidobacteriales. This data suggests that in our set of developed-nation-born babies, those fed by a non-secretor mother were at a disadvantage in the establishment of a healthy, bifidobacterialladen, microbiota early in life. This may possibly be due to difficulties in being seeded with a species of bifidobacteria with metabolic abilities appropriate for the type of milk being consumed. This work provides mechanistic insight into how milk components enrich specific beneficial bacterial populations in infants and reveals translational clues for glycan-based enrichment of bifidobacterial populations in at risk populations—such as premature infants.

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