Gut microbiome during infancy may predict future type 1 diabetes
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Key takeaways:
- Children diagnosed with type 1 diabetes have differences in their gut microbiome at age 1 year from those without diabetes.
- Gut microbiome composition during infancy may be used to predict future diabetes risk.
Children who develop type 1 diabetes may have biomarkers present in the gut microbiome as early as age 1 year, according to a study published in Diabetologia.
In a comparison of stool samples collected at age 1 year among a small group of children who developed type 1 diabetes in the future and children who would not develop diabetes, researchers observed differences in microbiome composition. The findings suggest analyzing the gut microbiome may help identify infants who have an elevated risk for developing type 1 diabetes.
“Screening children at birth for genetic risk and monitoring gut health over time would be helpful and allow for dietary or probiotic interventions to improve gut health,” Eric W. Triplett, PhD, professor and chair of the department of microbiology and cell science at the University of Florida, told Healio.
Triplett and colleagues analyzed data from infants participating in the All Babies in Southeast Sweden general population cohort who were born between October 1997 and October 1999. Stool samples were collected from infants’ diapers at about age 1 year. The Swedish National Patient Register and Swedish pediatric diabetes quality register were used to identify 16 participants with stool samples available who were diagnosed with type 1 diabetes as of December 2020 (mean age at diagnosis, 13.3 years). Data from the 16 infants who were diagnosed with diabetes were matched by geographic region, presence of siblings at birth, residence type, duration of breastfeeding and month of stool collection with a group of 32 control infants who did not develop type 1 diabetes.
When the diabetes and control groups’ stool samples were compared, 17 core genera had a positive mean decrease accuracy score that differentiated them between the two groups. Ruminococcus was a key factor for differentiating both diabetes and control participants, though it was more abundant in control infants than those who developed diabetes, the researchers reported. Flavonifractor and UBA1819 were the strongest factors differentiating control infants and both were more abundant in the control group. Alistipes and Fusicatenibacter were the strongest factors differentiating infants in the type 1 diabetes group. Alistipes was more abundant in the control group, whereas Fusicatenibacter had a higher total abundance among controls, but a higher relative abundance among the diabetes group.
Researchers identified 10 amplicon sequence variants that were significant in differentiating youth diagnosed with diabetes and controls. The highest mean decrease accuracy score for both groups was Agathobacter-434, which had a higher total and relative abundance among infants who developed type 1 diabetes. The next highest mean decrease accuracy score among the diabetes group was for Lachnospira-5640, which had a higher total abundance among the control group but a higher relative abundance for the diabetes group. The second-highest mean decrease accuracy score for the control group was for Anaerostipes-747, which had a higher total and relative abundance among the control group.
“Based on work from the All Babies in Southeast Sweden study, led by Johnny Ludvigsson, MD, PhD, of Linköping University, it seems that the stage is set very early in life for type 1 diabetes that can be diagnosed a decade later,” Triplett said. “In the case of this paper, we see specific gut bacteria associated with future type 1 diabetes. Once we learn more, we may be able to make a predictive model based on gut microbiome composition and other factors that would have higher accuracy than the currently available genetic risk scores.”
Triplett noted the study’s cohort was small and future studies need to include a larger general population cohort where stool samples are collected across time. Additionally, he said future studies are needed to examine the functions of the gut bacteria that are associated with future type 1 diabetes.
Perspective
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Approximately 8.75 million people globally live with type 1 diabetes, and while multifactorial, the gut microbiome may be among the contributors to disease development. While gut microbial composition is known to be altered in type 1 diabetes (van Heck JIP, et al. Diabetes Care. 2022;doi:10.2337/dc21-2225), available data also suggest changes in gut populations may occur early in infancy, acting as a catalyst in the development of type 1 diabetes (Mokhtari P, et al. Gut Microbes. 2021;doi:10.1080/19490976.2021.1926841).
Belteky and colleagues explored whether there were differences in the gut microbiome of infants who developed type 1 diabetes in the future vs. matched healthy controls.
The study is based on the All Babies in Southeast Sweden cohort. Of the 167 children within this group with future type 1 diabetes, 16 had stool samples from around 1 year of age available for analysis. Microbial examination using standard methodology revealed differences in the core microbiome between these samples when compared to a control cohort. Using software to predict the functional changes associated with these microbial differences, investigators noted that control infants had higher predicted expression of butyrate production and pyruvate fermentation pathways.
The findings suggest the possibility of a personalized approach. Microbial “fingerprinting” of stool samples to ultimately identify infants at high risk for developing type 1 diabetes. This approach has the potential for then creating a specific microbial intervention for these patients. It’s a fascinating approach to disease prevention and treatment that is early in development.
The potential significance of the findings is tempered by the fact that the cohort is small and geographically specific. Also, little is known about the dietary habits of these infants, which is important given the strong influence of diet on gut microbial composition. The microbiome story will develop as we are able to drill down to the species level and move from predicted functional pathways to true measures of metabolites in order to address cause and effect. Ultimately, the relevance of these data will come by fulfilling Koch’s postulates: Do the microbial changes identified actually cause disease when given to a naive host?
It is important to acknowledge that by enhancing methods for predicting who will develop type 1 diabetes, we can potentially intervene earlier and alter the course of disease, or perhaps thwart it all together. As such, this work is a critical first step.
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