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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE260491 | GEO | 2024/03/12

REPOSITORIES: GEO

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Project description:Dr. Lebrilla's lab is working on another set of transcriptomics experiments which will measure whether HMO (human milk oligosacharides) elicit a differential response on Caco2 in the presence of B.infantis. They wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which they have initiated a collaboration with the CFG Core H (David Smith). The influence, signaling and adhesion between Bifidobacterium infantis, a probiotic microorganism abundant in infant feces, and Caco2 epithelial cells. Our hypothesis is that HMOs act as signaling molecules for both Caco2 cells and B. infantis to indicate the presence in the gut, of a nutrient niche adapted for the nourishment and recruitment of HMO-consuming probiotic microorganism. HMOs therefore could play a role in the expression and binding to GBPs both on epithelial cells and in probiotic gut microorganisms. Preliminary transcriptomics data analysis obtained by using the Illumina Human Ref-8 Expression Bead Chip, has revealed that co-incubation of Caco2 cells with HMO upregulates genes belonging to chemokines, adhesion molecules, growth factors and glycan degradation, thus indicating that HMOs are actively recognized by these cells. We are working on another set of transcriptomics experiments which will measure whether HMO elicit a differential response on Caco2 in the presence of B.infantis. We wish to supplement the data obtained with the Illumina platform with glycan-related expression data obtained with the Gene-chips to achieve a more complete understanding on how Caco2 cells respond to the presence of HMOs and B.infantis. The transcriptomics data is being complemented by qPCR based bacterial-epithelial cells binding assays, and glycan arrays assays for which we have initiated a collaboration with the CFG Core H (David Smith). We are requesting the analysis of 16 RNA samples from Caco2 cells on the Glyco-gene chips, for testing respectively 4 independent biological replicates for each of the 4 different co-incubation conditions. RNA preparations from Caco2 cells were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.

Project description:On going efforts are directed at understanding the mutualism between the gut microbiota and the host in breast-fed versus formula-fed infants. Due to the lack of tissue biopsies, no investigators have performed a global transcriptional (gene expression) analysis of the developing human intestine in healthy infants. As a result, the crosstalk between the microbiome and the host transcriptome in the developing mucosal-commensal environment has not been determined. In this study, we examined the host intestinal mRNA gene expression and microbial DNA profiles in full term 3 month-old infants exclusively formula fed (FF) (n=6) or breast fed (BF) (n=6) from birth to 3 months. Host mRNA microarray measurements were performed using isolated intact sloughed epithelial cells in stool samples collected at 3 months. Microbial composition from the same stool samples was assessed by metagenomic pyrosequencing. Both the host mRNA expression and bacterial microbiome phylogenetic profiles provided strong feature sets that clearly classified the two groups of babies (FF and BF). To determine the relationship between host epithelial cell gene expression and the bacterial colony profiles, the host transcriptome and functionally profiled microbiome data were analyzed in a multivariate manner. From a functional perspective, analysis of the gut microbiota's metagenome revealed that characteristics associated with virulence differed between the FF and BF babies. Using canonical correlation analysis, evidence of multivariate structure relating eleven host immunity / mucosal defense-related genes and microbiome virulence characteristics was observed. These results, for the first time, provide insight into the integrated responses of the host and microbiome to dietary substrates in the early neonatal period. Our data suggest that systems biology and computational modeling approaches that integrate “-omic” information from the host and the microbiome can identify important mechanistic pathways of intestinal development affecting the gut microbiome in the first few months of life. KEYWORDS: infant, breast-feeding, infant formula, exfoliated cells, transcriptome, metagenome, multivariate analysis, canonical correlation analysis 12 samples, 2 groups

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

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