Previous research has suggested the gut microbiota’s role in the risk of developing metabolic and immune-related disorders later in life. However, no studies have characterized the early-life gut microbiome longitudinally in large populations. Three recent studies shed light on how early-life gut microbiota composition might help identify which children are at risk of developing obesity and type 1 diabetes later in childhood.

The first prospective cohort study, led by Dr. Merete Eggesbø from the Norwegian Institute of Public Health (Oslo, Norway), concludes that gut microbiome composition at 2 years of age can predict obesity at age 12, suggesting the gut microbiome may play an early role in promoting obesity.

The researchers examined the association between gut microbiota composition on six occasions during the first two years of life and body mass index (BMI)—using BMI z-scores as measures of relative weight adjusted for child age and sex—at age 12 in a birth cohort of 165 Norwegian children (from the NoMIC cohort) and their mothers.

Gut microbiota composition at days 10 and 2 years of age was associated with childhood BMI at age 12. Specifically, the gut microbiota taxa at 2 years of age explained 53% of the variation in childhood BMI. It was also found that BMI-associated taxa in children correlated with maternal taxa relating to excess maternal weight and obesity and excessive gestational weight gain.

The other two studies (here; here) have explored whether the gut microbiome in early life could be a predictive trigger of type 1 diabetes (T1D). With this goal in mind, longitudinal stool samples were collected from the largest microbiome study in children to date, which is part of the The Environmental Determinants of Type 1 Diabetes in the Young (TEDDY) study. The children under study included seroconverters, those diagnosed with T1D and controls.

In the first study, the researchers analyzed 16S ribosomal ribonucleic acid sequencing information in 12,500 stool samples from 905 children between 3 and 46 months of age.

The researchers detected that temporal development of the gut microbiome followed three distinct phases: one of development, which ran from 3 to 14 months; another one of transition, from 15 to 30 months; and that of progressive stabilization, from 31 months onwards. However, it cannot be inferred that gut microbiota maturation ends at 2.5 years of age. Previous data has shown that the gut microbiota is not established at 5 years of age and its maturation process becomes apparent even up to 20 years of age, experiencing another shift at 70 years into the elderly type.

Regarding maternal and postnatal influences on the developing gut microbiome, it was observed that, in the first phase, breastfeeding was associated with higher levels of bifidobacteria and that microbiota diversity increased when children began to incorporate solid foods. They also observed that children who had been born vaginally had a temporary increase in Bacteroides, which in turn was associated with greater gut diversity and maturation.

In the second study, the researchers focused on metagenomic sequencing data from 783 children over the first five years of life.

The gut microbiome of children who did not develop T1D later in childhood contained more genes related to fermentation and short-chain fatty acid production, whose protective role in metabolic conditions have been shown previously. Apart from considering intra-individual specific functions, the researchers found that a range of 20 microbial metabolic enzymes changed consistently over the first year of life. The lactate dehydrogenase enzyme decreased, whereas the transketolase enzyme, which is involved in the metabolism of fiber, increased.

In contrast, children who developed T1D had a gut microbiota rich in Bacteroides species with depleted levels of SCFA-producing bacteria.

On the whole, these findings provide preliminary evidence that the early-life gut microbiome may help identify children who are at risk of obesity and of developing islet autoimmunity or T1D later in life, which may subsequently facilitate early prevention efforts, especially through diet.

 

References:

Stanislawski MA, Dabelea D, Wagner BD, et al. Gut microbiota in the first 2 years of life and the association with body mass index at age 12 in a Norwegian birth cohort. mBio. 2018; 9:e01751-18. doi: 10.1128/mBio.01751-18.

Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018; 562:583-8. doi: 10.1038/s41586-018-0617-x.

Vatanen T, Franzosa EA, Schwager R, et al. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018; 562:589-94. doi: 10.1038/s41586-018-0620-2.