The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota

Abstract

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and disease.

Keywords: bifidobacteria; gut commensals; gut microbiota; infants; metagenomics; microbiome; microbiota; probiotics; virome.

FIG 1

Microbiota composition across the different infant body sites. A global overview of the relative abundances of key phyla of the infant microbiota composition in different body sites and at different stages of early life is shown. Concentric cake diagrams schematically represent interindividual variability.

FIG 2

General overview of the bioinformatic pipelines for the 16S rRNA gene microbial profiling and shotgun metagenomics. Starting from DNA extraction of a microbial community and subsequent sequencing, the pipeline generates taxonomic profiling of the microbiota and the reconstruction of microbial genomes with corresponding functional analyses of the genes.

FIG 3

Window of opportunity for microbiota modulation from gestation to childhood. The schematic representation shows a list of prenatal, neonatal, and postnatal factors that contribute to the bacterial gut composition in infants.

FIG 4

Colonization routes of maternal microbiomes to the infant. The mother portrayal exhibits the maternal microbiome locations and the related routes that result in the vertical transmission of the microbiota to the infant.

FIG 5

Chemical structures of human milk oligosaccharides and related enzymatic degradation. On the left are listed the bifidobacterial species that encode enzymes for HMO breakdown retrieved into the infant gut, while on the right are reported the products of the enzymatic reactions.

FIG 6

Strain-specific tracing of bifidobacteria from mother to infant. Each panel displays the protocol for shotgun sequencing of the high-abundance bacterial target and their corresponding tracing in mother and infant gut microbiota samples.

FIG 7

Infant health status and microbiota establishment. The schematic representation shows several diseases related to the colonization of bacteria that are claimed to be pathogens.

FIG 8

The infant gut core microbiota. A 16S rRNA gene-based tree involving the infant bacterial core microbiota is displayed. The colors of the branches indicate the six main phylogenetic groups of the infant gut microbiota. An electron microscopic image of the key infant gut bacterial taxon is displayed for each branch of the tree.

FIG 9

Extracellular structures identified among members of the Bifidobacterium genus. The bifidobacterial phylogenetic tree is based on the core gene sequences conserved in each bifidobacterial (sub)species. Colored dots show the presence of the different extracellular structures distributed among the Bifidobacterium genus. The bifidobacterial colors are related to the ecological origin of each bifidobacterial (sub)species.

FIG 10

Contribution of phages to gut microbiota development through human aging. Putative factors influencing the virome biodiversity from infant to adult are schematically represented as factors of the curve's formula. Phage and bacterial loads are schematically represented to express the concept that while the phage load decreases during aging, the gut microbial population increases in complexity and abundance. The number of bacterial or phage particles schematically represents the number of species and complexity of the population.