Maternal diet structures the breast milk microbiome in association with human milk oligosaccharides and gut-associated bacteria

OBJECTIVE: We have previously shown that a high fat maternal diet (HFD) during gestation and lactation has a long-term impact on the offspring gut microbiome. However, the relative contribution of breast milk is unknown. In this study, we sought to determine mechanisms by which diet may modulate composition of the milk microbiota. Specifically, given the role of human milk oligosaccharides (HMOs) in protection against both dysbiosis and necrotizing enterocolitis, we hypothesized that there may be an interaction between maternal HFD, HMOs, and the breast milk microbiome. STUDY DESIGN: Two dietary treatments were tested in single-blinded cross-over dietary intervention studies of lactating women. The first cohort (n = 7) received a high fat or carbohydrate diet, with a 1-2 week washout period. The second cohort (n = 7) received 60% of their daily caloric intake from either glucose or galactose, with a 1 week washout period. Milk samples collected after each dietary treatment were subjected to 16S metagenomic analysis and HPLC/ MS to profile the microbiome and HMO composition, respectively. RESULTS: High fat versus carbohydrate diet significantly alters the milk microbiome (p = 0.038, Figure A), including significant shifts in several gut-associated taxa (Figure B). High fat diet decreases concentration of sialylated HMOs (p = 0.02, Figure C), and glucose versus galactose diet significantly alters concentration of fucosylated HMOs (p = 0.02, Figure C). Intriguingly, sialylated HMO concentration is significantly correlated with microbiome composition in both dietary cohorts (p = 0.0015, Figure D), suggesting these HMOs play a key role in structuring the milk microbiome. CONCLUSION: Maternal diet significantly alters the milk microbiome, HMO composition, and abundance of gut-associated taxa. These findings suggest that dietary influence on the milk microbiome is mediated in association with an altered proliferation of bacteria due to changes in sialylated HMO concentration. Additionally, we speculate that shifts in the maternal gut microbiome are translated to the milk microbiome via trafficking of enteric bacteria, resulting in the observed shifts in gut-associated taxa in breast milk.( Figure persented).