Comparing milk oligosaccharides across various mammal species and assessing their impacts on intestinal health

Milk oligosaccharides (MOs), the third most abundant solid component of breast
milk, are of great importance for infant growth. To date, knowledge on MOs profiles
in different mammalian species is limited. MOs can alleviate colonic inflammation
by shaping the composition of the gut microbiota. However, it remains unclear
whether the gut microbiota mediates the protective activity of MOs and whether the
beneficial effects change with different types of MOs.
To understand these questions, first, an LC-ESI-MS/MS method was developed to
simultaneously analyze 11 MOs in milk samples from human, dairy cow, sheep, mare,
camel, yak and buffalo. The results showed that human milk presented an abundance
of MOs 7.6 to 15.8 times higher than in the milk of other animals. Fucosylated neutral
forms were dominant. Dairy cow, camel, yak, sheep, buffalo and mare milks were
similar in their MOs profiles and rich in sialylated forms. Compared to other animals,
the composition of MOs in sheep is more similar to that of human milk. Moreover,
heat treatment at 65 °C for 30 min had no effect on the concentration or distribution
of MOs, whereas heat treatment at 135 °C for 60 s induced a decrease in their
concentration and distribution.
Then the beneficial functions of 2′-fucosyllactose (2′-FL), the predominant MO in
human breast milk, were assessed for alleviating colon inflammation, and the roles of
gut microbiota in this process were further explored. The obtained results showed that
2'-FL improved colitis symptoms in a gut microbiota-mediated manner by reshaping
the composition of gut microbiota, as well as a reorganization of mucin-utilizing
bacteria. The underlying protective mechanism was associated with promoting an
increase in goblet cell number and MUC2 secretion. Additionally, 2'-FL exerted antiinflammatory effects by targeting the TLR4/MyD88/NF-κB-related inflammatory
pathway.
Finally, to further compare the effect of individual MOs on enhancing mucin
expression, the effects of 2'-FL (a representative fucosylated neutral MO), 3'-
sialyllactose (3'-SL, a representative sialylated MO), galacto-oligosaccharide (GOS,
commonly added into infant formula) and lactose (Lac, their structure core) on
promoting MUC2 secretion in goblet cell models under homeostasis and
inflammatory state were assessed. The results showed that 2′-FL and GOS, but not 3′-
SL and Lac, were able to increase the mRNA expression of MUC2, TFF3 and CHST5
only in inflammatory conditions. Furthermore, 2′-FL was able to exert its function in
goblet cells via several processes, such as promoting mucin secretion through NLRP6
and suppressing the TLR4 related inflammatory pathway. Together, these results provide new insights into the functions of MOs from different species and could potentially help to better utilize them in infant formula.