Maternal high-fat diet during lactation reduces sialylated milk oligosaccharides and shapes early-life microbiota in rat offspring†

Abstract

Human milk oligosaccharides (HMOs) promote the development of the infant gut microbiota, notably through the growth of beneficial bacteria. However, the interaction between maternal diet, HMOs and the offspring's gut microbiota remains incompletely understood. We hypothesize that a high-fat (HF) diet influences the composition of HMOs and shapes gut microbiota in offspring. In lactating rat mothers fed with a HF or a low-fat (LF) diet, we measured at mid-lactation, the levels of milk sialylated oligosaccharides (SL-MOs) and the expression of enzymes for synthesizing SL-MOs in the mammary gland. In rat pups from LF or HF mothers, we analysed the caecal microbiota and measured levels of faecal short-chain fatty acids (SCFAs). In addition, in humans, we quantified 24 HMOs in the colostrum of lean and obese mothers. In rat mothers, HF feeding significantly reduced the breast milk 6′SL level but not the 3′SL one and increased the gene-expression level of the St3Gal1 enzyme in the mammary gland. In HF rat pups, the caecal microbiota was drastically modified with increases in α- and β-diversities as well as in the abundance of Parabacteroides and Lachnospiraceae. Levels of faecal SCFAs including acetate, butyrate, isobutyrate, valerate and isovalerate were also increased in HF pups. In humans, maternal obesity only slightly increased DFLNHa concentration in the colostrum. In conclusion, our data suggest that a hyperlipidic diet during lactation may reduce the level of sialylated oligosaccharides in breast milk and alter the abundance of several groups of bacteria in the infant's gut. We also demonstrated that, in humans, obesity did not highly affect levels of HMOs in the colostrum reinforcing previous findings suggesting that being overweight does not influence drastically the HMO profile in breast milk.