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Human Gut Microbiome Develops in Three Stages

NEW YORK (GenomeWeb) – The human gut microbiome goes through three stages of development in early life, according to a new study.

An international team of researchers collected and analyzed longitudinal stool microbiome samples collected from more than 900 children living in Europe and the US taking part in The Environmental Determinants of Diabetes in the Young (TEDDY) study. As the researchers reported in Nature yesterday, they found that the gut microbiome passes through three stages of development, marked by increasing bacterial diversity and influenced by breastfeeding.

"We know that the first few years of life are important for microbiome establishment. You are born with very few microbes, and microbial communities assemble on and in your body through those first years of your life," senior author Joseph Petrosino, a professor of molecular virology and microbiology at Baylor College of Medicine, said in a statement. "In this study, we took a closer look … at the establishment of the microbiome over the first few years of life and the early life exposures associated with that sequence of events."

For this study, the researchers examined 16S rRNA gene sequencing or metagenomic sequencing of 12,500 stool samples collected from 903 infants and children between the ages of three months and 46 months. In a clustering analysis, the samples formed 10 groups with differing levels of bacterial richness and diversity.

Using linear mixed-effects modeling of the top phyla and the Shannon diversity index, the researchers uncovered three phases of microbiome progression: a developmental stage lasting from 3 months to 14 months of age, a transitional phase from 15 months to 40 months, and a stable phase after 31 months of age. They noted that, with increasing age, the bacterial diversity of the microbiome expanded.

Bifidobacterium dominated the developmental stage, and later stages became more microbially diverse. At the third stage, gut microbiomes had high diversity and were dominated by genera from the Firmicutes.

Breastfeeding, the researchers found, was significantly associated with the gut microbial profile. It explained 10 percent of the variance in microbial diversity between the ages of 3 months and 18 months, and especially between 3 months and six months. In particular, it was linked to increased levels of Bifidobacterium, species of which are known to exist in breast milk. Bifidobacterium remained high among infants who were breastfed along with receiving formula or solid food.

As breastfeeding stopped among their cohort, the researchers noticed an increase in 100 bacterial species, mostly from the Firmicutes phylum. This, they said, suggests that the stopping of breastfeeding rather than the introduction of solid food spurs the maturation of the gut microbiome.

"Targeting the nutrients in breast milk that encourage the growth of healthy bacteria in the infant gut, or providing probiotic containing Bifidobacterium, represent important avenues for future research aimed at restoring the beneficial properties of being breastfed when breast milk is not available," first author Christopher Stewart from Newcastle University said in a statement.

Other variables also influenced the infants' microbiomes. Infants born vaginally had higher levels of Bacteroides and higher microbial diversity overall, while infants with siblings or pets had microbiomes that matured more quickly.

The TEDDY study from which this cohort hails aims to tease out what causes the development of type 1 diabetes in genetically at-risk children. Here, the researchers noted subtle differences in the abundance of microbial genera between cases with islet auto-immunity (IA) or T1D, or controls. T1D cases, they found, had higher levels of Streptococcus and Lactococcus species.

In a companion study that also appeared in Nature this week, a Broad Institute-led team reported that the microbiomes of control children harbored more genes involved in the fermentation and biosynthesis of short-chain fatty acids. In combination with other studies and a mouse model of T1D, the researchers said this indicates that short-chain fatty acids might be protective against early T1D development.