Early Childhood Gut Microbiomes Show Strong Geographic Differences Among Subjects at High Risk for Type 1 Diabetes

Kaisa M. Kemppainen; Alexandria N. Ardissone; Austin G. Davis-Richardson; Jennie R. Fagen; Kelsey A. Gano; Luis G. Léon-Novelo; Kendra Vehik; George Casella; Olli Simell; Anette G. Ziegler; Marian J. Rewers; Åke Lernmark; William Hagopian; Jin-Xiong She; Jeffrey P. Krischer; Beena Akolkar; Desmond A. Schatz; Mark A. Atkinson; Eric W. Triplett

Disclosures

Diabetes Care. 2015;38(2):329-332. 

In This Article

Results

Sex (P = 0.0092) and age at first introduction to oats (P = 0.0042), gluten (P = 0.0001), and milk products (P < 0.0001) were the only clinical characteristics significantly different by geographical location. To characterize the development of the gut microbiome over time, 16S rRNA sequencing read values of bacterial genera were grouped according to age of subject (in months) at the time of sample collection (Fig. 1A). Bacteroides was the predominant genera at all sites (average abundance 22.7%, SE 0.7%). The abundance of Bifidobacterium (P = 0.0172), Veillonella (P = 0.0048), Faecalibacterium (P = 0.0122), Streptococcus (P = 0.0003), and Akkermansia (P = 0.0196) was significantly different by geographical location after adjusting for significant clinical and dietary variables. Although Bacteroides abundance was not significantly different (P = 0.0530) by site, Colorado had a significantly higher abundance than all other sites (P = 0.0126), except Finland.

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.

The permutation test of the SDI of bacterial genera identified at each site showed that all sites differ from each other across time (Fig. 1B). Furthermore, the difference remained significant after adjustment for delivery mode and age at first introduction to milk products (P = 0.0045). Colorado and Finland had a significantly lower SDI than all other sites (P = 0.0258). Georgia/Florida and Germany had a more diverse profile, characterized by a relative abundance of Clostridium, Bifidobacterium, and Veillonella of >8.0% each (Fig. 1A). In Sweden and Washington state, the fecal profile was dominated by Bifidobacterium until 8 and 10 months of age, respectively, and the overall abundance was significantly higher than in Colorado and Finland (P = 0.0199).

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