In a recent study published in Cell, researchers used a multi-omics approach to profile the gut microbiomes and metabolomes of mothers and infants to determine the vertical and horizontal transmission of bacterial species and strains, as well as individual genes and understand the dynamics of the intestine set of microbiome that shape the baby’s development before and after birth.
Study: The mobile genetic elements of the maternal microbiome shape the infant intestinal microbial composition and metabolism. Image credit: Design_Cells/Shutterstock
background
The vertical transmission of gut bacteria from mother to fetus during pregnancy and the horizontal transfer of microbes through breast milk play a vital role in the physical and cognitive development of the infant long after birth. Studies have shown associations between the composition of breast milk gut microbiota and the development of the infant’s immune system, as well as autoimmune conditions and allergies. In addition, allergies and autoimmune disorders have also been linked to exogenous proteins in infant formula.
Metabolites produced by the gut microbiota are also associated with the infant’s cognitive development. However, the development of gut microbiomes and metabolomes in the perinatal stage and their role in child development is still unclear.
About the study
In the present study, researchers used longitudinally collected infant serum samples and fecal samples from 137 mothers and 74 infants, including 70 mother-infant pairs. The samples underwent several analyses, including deep metagenomic sequencing, assays to measure circulating cytokines, markers of intestinal inflammation and intestinal permeability, as well as untargeted profiling of faecal metabolites.
We assessed changes and associations between metabolomic and metagenomic profiles of mothers and infants over time. Two approaches were used to analyze the metabolomic data: reference standards were used to annotate peaks and mass-to-charge relationships were mapped to the human metabolome database to identify metabolomic features of single compounds.
In addition, single nucleotide polymorphism (SNP) haplotypes of dominant strains of bacterial species were analyzed to identify identical strains between mothers and infants. The events that included the appearance of these strains in the infant’s gut microbiome were observed. In addition, we also analyzed the influence of the relative abundance of maternal gut microbial species on the structure of the infant gut microbiome to determine the maternal contribution to the assembly of the infant gut microbiome.
Contig pairs of mothers and infants that had shared gut microbe genes were aligned pairwise to confirm gene transfer between mothers and infants. Shared genes were mapped to databases such as uniprot, the Kyoto Encyclopedia of Genes and Genomes, and Evolutionary Genealogy of Genes: Unsupervised Orthologous Groups (eggNOG) to determine the involvement of genes with mobilome-related functions such as conjugation and horizontal gene transduction. transfer The biological abundance and prevalence of microbial genes were calculated to better understand the relevance of interspecies gene transfer from mother to infant.
Metabolomic profiles of mothers and infants were compared and infant-specific characteristics in metabolomic profiles were investigated to determine longitudinal patterns. In addition, tandem mass spectrometry was used to determine the association between breast milk and the infant metabolome. The effects of diet on infants were investigated by comparing metagenomic and metabolomic profiles and markers of systemic and intestinal inflammation in breast-fed infants with those of infants fed hydrolyzed or regular formula.
results
The results reported the large-scale transfer, from mother to infant, of mobile genetic elements normally associated with genes involved in diet-related adaptations. The diversity of infant metabolomes was lower than that of mothers, but infant metabolomes contained a large number of novel microbe-metabolite associations and unique metabolites not found in maternal metabolomes. One such association that was unique to infant metabolomes was the inverse relationship between Bifidobacterium longum and inosine, which has immunomodulatory and neuroprotective properties.
Markers of inflammation such as cytokine signatures and metabolome profiles of breastfed infants were significantly different compared to infants fed non-extensively hydrolyzed regular formula. Breastfed infants showed increased markers of intestinal inflammation such as beta-defensin 2 and fetal calprotectin, which were inversely correlated with pro-inflammatory markers. Additionally, microbes found in breast milk were positively associated with eicosanoids and other gut inflammatory mediators in infants. Breastfed infants experienced early immune maturation, leading to greater immune tolerance.
Metabolic profiles also revealed changes in faecal bile acids in pregnant women, which correlated with increased taurine conjugation. The gut microbiota showed an increase in Bilophila wadsworthia, a bacterial species that reduces sulfates and degrades taurine.
Conclusions
Overall, the results reported that maternal microbiota and dietary factors influence the co-development of infants’ microbiome and metabolome and affect their neurodevelopment and immune maturation. Furthermore, maternal influences on the gut microbiome and metabolic activities of infants are also exerted through horizontal cross-species gene transfer from mother to infant. Furthermore, the identification of microbe-metabolite interactions unique to infants indicates that microbes play an important role in early development, which needs to be further explored.
Journal reference:
- Vatanen, T., Jabbar, KS, Ruohtula, T., Honkanen, J., Avila-Pacheco, J., Siljander, H., Stražar, M., Oikarinen, S., Hyöty, H., Ilonen, J. , Mitchell, CM, Yassour, M., Virtanen, SM, Clish, CB, Plichta, DR, Vlamakis, H., Knip, M. and Xavier, RJ (2022). The mobile genetic elements of the maternal microbiome shape the baby’s gut. Microbial assembly and metabolism. cell doi: