Microbiota of infants consuming secretors or non-secretors mothers milk impacts gut and immune system in mice.

Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which in turn changes the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology and gene expression, day 21-old germ-free mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity however, SMM mice had higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there were higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 (ILC2) were increased in MFM mice supplemented with HMOs while in the spleen, they were increased in SMM+HMOs mice. Similarly, serum immunoglobulin A (IgA) was also elevated in MFM+HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data shows that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response and intestinal gene expression in a mouse model. Overall design: To understand the impact of microbiota-derived from infants who were fed by secretor or non-secretor mothers or those consuming infant formula in mice, we transplanted fecal materials from these infants into germ-free mice on day 1 and day 7. One set of mice from each group was also supplemented with pooled Human Milk Oligosaccharides (HMOs), daily for 14 days. Total RNA from the distal small intestine (ileum) and large intestine (colon) were extracted and subjected to mRNA sequencing. Ileum and colon tissues from germ-free mice were included as the control. The following experimental groups were included: Germ -Free Control (GF), Secretor Microbiota (SMM), Non-Secretor Microbiota (NSM), Milk Formula Microbiota (MFM), SMM+HMOs, NSM+HMOs and MFM+HMOs.