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

Conclusions

This study highlights the great variability in the composition and diversity of gut microbiomes among the six TEDDY study sites. So far, studies examining the association between the gut microbiome and type 1 diabetes autoimmunity have focused on small geographical regions.[2–6] Country- and lifestyle-specific factors are a major player in shaping the composition of the gut community,[7–11] but the extent to which they affect the microbiome of infants at high risk for type 1 diabetes was previously unknown. Our study is the first to investigate the fecal microbial profile of high-risk children across two continents and multiple countries.

Our data suggest that children at high risk for type 1 diabetes have study site–specific patterns of gut colonization showing intercontinental similarities but intracontinental differences. Geographical origin significantly associated with the diversity of bacterial communities and the relative abundance of numerous bacterial genera (Fig. 1A). Low bacterial diversity was characteristic of subjects from Finland and Colorado. Previous studies have reported similar reductions in microbiome diversity in northern European infants compared with infants from southern European countries (Sweden vs. Spain and Finland vs. Germany, respectively).[9,10] While Finland has the highest incidence of type 1 diabetes in children,[17] it remains to be seen whether SDI is associated with disease incidence. Perplexing differences, not explained by clinical characteristics, exist between the neighboring countries Sweden and Finland. Compared with their Swedish neighbors, Finnish subjects had a significantly higher abundance of Bacteroides (P = 0.0508) and Veillonella (P = 0.0160), and a lower abundance of Bifidobacterium (P = 0.0199), Akkermansia (P = 0.0014), and Ruminococcus (P = 0.0248). The fecal profile of Swedish subjects was more similar to those from Washington state (both groups of subjects were dominated by Bifidobacteria at early time points), suggesting a more typical colonization pattern of the infant gut.[18]

Clearly, microbiome diversity varies with geographical location, even in a population of homogenous HLA class II genotypes. Geography represents a culmination of underlying environmental and cultural factors that, on their own, are difficult to account for. The prime source of variability in these data remains unknown because significant differences in microbiome composition exist even after adjusting for numerous early-life and dietary variables. Future studies must carefully consider the impact of geographical location on the microbiome of children who are genetically at higher risk for type 1 diabetes as location may confound analyses of disease-associated microbiome states. Furthermore, whether the microbiome is causative or merely an indicator of underlying type 1 diabetes etiology, these microbiome differences suggest a geographically tailored approach to diagnostics or preventative therapies.

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