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Researchers Uncover Infant Gut Microbiome Alterations Linked to Type 1 Diabetes

NEW YORK (GenomeWeb) – Through a longitudinal study, researchers from the US and Finland have identified changes that take place in the gut microbiome as infants develop type 1 diabetes.

The team, led by Ramnik Xavier from the Broad Institute and Massachusetts General Hospital, followed a cohort of 33 infants genetically at risk for type 1 diabetes from birth to age three and regularly characterized their gut microbiomes. As they reported in Cell, Host & Microbe today, the researchers found that while the composition of the gut microbiome varied between infants, it was fairly stable over time within an individual. But infants who progressed to type 1 diabetes experienced a drop in microbial diversity just prior to diagnosis.

"This study is unique because we have taken a cohort of children at high risk of developing type 1 diabetes and then followed what changes in the microbiome tip the balance toward progression to the disease," Xavier said in a statement.

Xavier and his colleagues followed 33 infants from Finland and Estonia at risk of developing the disease as gauged by HLA risk genotyping for about three years. During this time, parents collected the babies' stool samples once a month for analysis.

During the course of the study, 11 infants had positive serum autoantibody results, a first step in the development of type 1 diabetes. Four of those babies went on to develop the disease.

The researchers performed 16S rDNA sequencing on the 989 microbiome samples collected using paired-end, partially overlapping reads on the Illumina MiSeq platform. They further did shotgun metagenomic sequencing on a subset of 19 samples, including all 11 seroconverters. They also performed metabolomic analysis of stool and serum samples from the infants.

Overall, Xavier and his colleagues reported that age seems to be the main factor that drives the composition of the infant gut microbiome, as it accounted for about 18 percent of the variation they observed.

Even as the microbiome becomes more diverse with age, the researchers noted that the relative abundance of metabolic modules within the microbiome stayed about constant over time and between individuals, indicating that the metabolic capability of the microbiome is stable even as the composition shifts.

"Whether the bacterial community is very small, as it is in early infancy, or if it's larger as it is later in life, the community is always serving the same major functions regardless of its composition," added Aleksandar Kostic, a postdoctoral fellow in Xavier's lab. "No matter which species are present, they encode the same major metabolic pathways, indicating that they're doing the same jobs."

The researchers also reported that the composition of the microbiome seemed to stabilize around age three, and that the microbial community the children had at that age retained microbial members acquired after birth.

In infants who developed type 1 diabetes, though, the researchers noticed a 25 percent drop in gut microbiome diversity.

They traced this decline in diversity to an overabundance of groups like Blautia, the Rikenellaceae, and the Ruminococcus and Streptococcus genera, all of which are commensal bacteria that can turn pathogenic. Additionally, other groups like the Lachnospiraceae and Veillonellaceae that usually promote gut health declined in abundance.

This decline in diversity correlated with a shift in the abundance of certain metabolic pathways like sugar transport systems and amino acid biosynthesis pathways. 

Interestingly, Xavier and his colleagues noted that seroconverters seemed to occupy a middle space between infants who developed type 1 diabetes and non-converters, suggesting to the researchers that these shifts are linked to type 1 diabetes disease state and that these changes may be harbingers of the disease's development.