The TEDDY study – which includes kids in Finland and Sweden – is finding factors that influence type 1 diabetes.
Type 1 diabetes (T1D), which is often diagnosed in childhood, results from a complex interaction of genetic and environmental factors, including the gut microbiome. To identify influencers of T1D development, the Environmental Determinants of Diabetes in the Young (TEDDY) study gathers prospective data on a cohort of children in the United States, Germany, Finland, and Sweden. Now, two TEDDY papers in Nature reveal features of the early gut microbiome in general and in kids with T1D. To identify bacteria in the gut microbiome, researchers analyzed sequence data from 12,005 monthly stool samples from 903 children as they grew from age 3 to 46 months.
Tommi Vatanen, who has a PhD from Aalto University, Finland and is now with the Broad Institute, Boston, led microbiome data analysis on the T1D paper. The size of the study was unique, Vatanen says: “We had about 10 times more samples than other microbiome studies.” He adds that the study data are available on request.
Infants and children, like adults, have individualized gut microbiomes, report the TEDDY scientists. Of many factors they analyzed that influence the bacterial communities in the early gut such as antibiotic use and exposure to pets and siblings, breastfeeding had the strongest effect. “It promoted the presence of Bifidobacterium,” Vatanen says. And other studies suggest these bacteria can be beneficial, such as against diarrhea or constipation.
Much more to learn
Because children varied widely in their microbiome composition, TEDDY researchers found only statistically weak links between specific bacteria and T1D. For a disease this complex, Vatanen says, the microbiome is just one of many influences. Nonetheless, the paper also reports a weak link between not developing T1D during the study period and having a microbiome with bacteria that ferment nondigestible carbohydrates to short-chain fatty acids (SCFAs) such as butyrate and acetate. These data reinforce previous studies from humans and mice showing that SCFAs might protect against T1D development.
Vatanen continues to work on TEDDY, including studying connections between host genotypes and microbiomes. Future studies in TEDDY and other cohorts might explore nonbacterial members of the gut microbiome such as viruses and fungi, and identify microbes that are acquired during birth and the first days of life, Vatanen says. Long-term, he is interested in researching the possible use of fecal microbial transplants to treat disease or help establish a healthy infant microbiome. Microbial transplants can be effective for inflammatory bowel disease and C. difficile infections in adults, he says, and require much more research before use in children. “But at some point,” he says, “we may go in that direction.”
Vatanen R, Franzosa EA, Schwager R, Tripathi S, Arthur TD, Vehik K, Lernmark Å, Hagopian WA, Rewers MJ, She J-X, Toppari J, Ziegler A-G, AkolkarB, Krischer JP, Stewart CJ, Ajami NJ, Petrosino JF, Gevers D, Lähdesmäki H, Vlamakis H, Huttenhower C, Xavier RJ. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018; 562(7728): 589 DOI: 10.1038/s41586-018-0620-