Study: Gut Microbiota of People With T1D Varies Significantly From Healthy Controls

The findings could lead to new insights into how type 1 diabetes develops.

A new report suggests the gut microbiota of patients with type 1 diabetes (T1D) are significantly different from those of healthy controls, a finding that could play an important role in understanding the pathogenesis of the disease.

The study was published in The Journal of the Federation of American Societies for Experimental Biology.

It is not yet clear exactly what factors lead to the development of T1D, but study co-author Kartik Shankar, PhD, of the University of Colorado Anschutz Medical Campus, and colleagues explained that both genetic factors and immune dysfunction are believed to play a role.

In recent years, the scientific community has paid increasing attention to the potential influence of the gut microbiota on immune dysfunction. The microbiota is believed to play a role not only in a person’s risk of developing recurrent infections such as Clostridioides difficile, but also in developing certain types of diseases, such as autoimmune disease.

Shankar and colleagues wanted to see whether there might be a link between the gut microbiome and the risk of developing T1D. They also sought to determine the associations, if any, between gut microbes and clinical and dietary factors in T1D, and to see whether certain features might enable the prediction of T1D.

The investigators recruited 30 adolescents with T1D, along with 35 adolescents without T1D, to serve as healthy controls. The patients each provided stool samples, which then underwent microbial profiling using deep shotgun metagenomic sequencing. The authors analyzed the results to determine the type and abundance of specific bacterial species in the samples, and then conducted correlation analysis and modeling to see whether specific features might be predictive of the disease.

The analysis showed that patients with T1D had greater alpha diversity than healthy adolescents, based on the Simpson Diversity Index. Alpha diversity is a measure of the overall heterogeneity within a sample. Beta diversity, on the other hand, was similar between the 2 cohorts. Beta diversity refers to the diversity between individual samples.

Using linear discriminant analysis effect sizes, the investigators found that there were significant differences in the microbial communities of the 2 groups at different taxonomic levels. Seven taxa were enriched at the species level in patients with T1D, while 3 were enriched in healthy controls.

“Further, 33 out of 400 microbial metabolic pathways were significantly different between the 2 groups,” the authors found. “Importantly, biosynthesis of amino acids, vitamins, enzyme cofactors, and electron carriers were downregulated whereas fermentation pathways were upregulated in adolescents with T1D as compared to healthy adolescents.”

A further analysis suggested that specific bacterial species were linked with glycated hemoglobin levels, skin carotenoids, dietary factors, and physical activity, the investigators said, but they added that “most of the bacterial species associated with these measures were different between the 2 groups.”

Collectively, the authors said the evidence suggests “extensive alteration” in both the composition and the functional capacity of the gut microbiota of people with T1D. They said their findings offer new insights that could help investigators better understand and predict how the disease develops.

Reference:

Pon Velayutham AB, Mokhtari P, Metos JM, Jambal P, Shankar K. Gut microbial and metabolic signatures are altered in adolescents with type 1 diabetes. FASEB J. Published online May 13, 2022. doi:10.1096/fasebj.2022.36.s1.r3170