Early childhood gut microbiomes show strong geographic differences among subjects at high risk for type 1 diabetes

Abstract

Objective: Gut microbiome dysbiosis is associated with numerous diseases, including type 1 diabetes. This pilot study determines how geographical location affects the microbiome of infants at high risk for type 1 diabetes in a population of homogenous HLA class II genotypes.

Research design and methods: High-throughput 16S rRNA sequencing was performed on stool samples collected from 90 high-risk, nonautoimmune infants participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study in the U.S., Germany, Sweden, and Finland.

Results: Study site-specific patterns of gut colonization share characteristics across continents. Finland and Colorado have a significantly lower bacterial diversity, while Sweden and Washington state are dominated by Bifidobacterium in early life. Bacterial community diversity over time is significantly different by geographical location.

Conclusions: The microbiome of high-risk infants is associated with geographical location. Future studies aiming to identify the microbiome disease phenotype need to carefully consider the geographical origin of subjects.

Figure 1

A: A heat map of the relative abundance of the most abundant bacterial genera shows a distinct pattern of development at each study site. 16S rRNA read values were grouped according to age of subject (in months) at the time of sample collection. If a subject had more than one sample within 1 month, the read values were averaged to prevent over-representation of a single individual. Bacterial genera denoted in black font are represented in the top 10 most abundant genera at all sites, and those denoted in blue font represent genera from the 10 most abundant at only some sites. Symbols indicate a statistically significant difference in bacterial abundance by geographical site after adjusting for age at stool collection and other significant covariates, as follows: *P < 0.05, **P < 0.01, ***P < 0.001, +P = 0.053. B: Changes in the SDI of genus-level microbial communities over time differ significantly at each site (P < 10⁻⁵). Diversity remains significantly different after adjusting for mode of delivery and age at first introduction to milk products (P = 0.0045). The left panel depicts a histogram of 10,000 F statistics obtained after randomly permuting the site labels. The blue line indicates the 95% quartile of this F statistic, and the arrow indicates the observed F statistic. The right panel depicts, for every site, a polynomial of degree 3 adjusted to the observed SDI, days after birth.