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Gut microbiota shifts likely precede type 1 diabetes onset

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February 5, 2015

Changes in gut microbiota appear to be associated with the onset of type 1 diabetes, according to findings published in Cell, Host & Microbe.

Infants genetically predisposed to the disease showed a drop in microbial diversity, with a disproportionate decline in the number of species that support gut health, in the largest longitudinal study of the microbiome yet, according to researchers.

“This is the first study to show how specific changes in the microbiome are affecting the progression to symptomatic type 1 diabetes,” Jessica Dunne, PhD, director of discovery research at JDRF, which funded the study, told Endocrine Today.

Jessica Dunne

Jessica Dunne

Aleksandar D. Kostic, PhD, from the Broad Institute of MIT and Harvard, with Ramnik Xavier, MD, PhD, and colleagues from Massachusetts General Hospital and the DIABIMMUNE Study Group followed 33 infants, from a larger cohort of Finnish and Estonian children, throughout their first 3 years of life.

The researchers regularly evaluated the composition of the infants’ gut microbiota using stool samples. Modeling trajectories of microbial abundances showed a subset of microbial relationships shared across most infants.

Strain composition varied between individuals but was stable within individuals during the 3 years; metabolic composition and pathway abundance also remained stable with time.

Alex Kostic

Aleksander D. Kostic

“Whether the bacterial community is very small, as it is in early infancy, or if it’s larger, as it is later in life, the community is always serving the same major functions regardless of its composition,” Kostic said in a press release. “No matter which species are present, they encode the same major metabolic pathways, indicating that they’re doing the same jobs.”

The investigators observed a 25% drop in the number of distinct species present in the microbiome 1 year before onset in the few infants who developed type 1 diabetes during this time.

The population shift involved a reduction in bacteria known to help regulate health in the gut and a rise in potentially harmful bacteria known to encourage inflammation.

“Current research data suggest that changes in the gut microbiota precede the development of autoimmunity,” Dunne said.

Ramnik Xavier

Ramnik Xavier

“We know from previous human studies that changes in gut bacterial composition correlate with the development of type 1 diabetes, and that the interaction between bacterial networks may be a contributing factor in why some people at risk for the disease develop it and others don’t,” she added.

Although evidence of increased autoimmune diseases with microbiota transfer has been demonstrated in animal studies, human studies that show associations have been retrospective and, therefore, lacking causality.

“This study is unique because we have taken a cohort of children at high risk of developing type 1 diabetes and then followed what changes in the microbiome tip the balance toward progression to the disease,” Xavier said in the release.

The detection of patterns in microbiome development could have diagnostic or therapeutic implications, according to the researchers.

Learning which species are absent and flourishing in the gastrointestinal tract of children with type 1 diabetes could help in slowing disease progression after onset through microbiome manipulation, Xavier said in the release.

“We’re agnostic at this point about the type of therapy that could potentially be developed,” Dunne said. “It could be a probiotic that helps restore balance to the gut microbiota or a drug that alters pathways that the gut microbiota effects.” – by Allegra Tiver

For more information:

Jessica Dunne, PhD, can be reached at JDRF, 26 Broadway, 14th Floor New York, NY 10004; email: JDunne@jdrf.org

Disclosure: The researchers report no relevant financial disclosures.

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PERSPECTIVE
Ruchi Mathur

Ruchi Mathur

The human being is host to trillions of microorganisms, the majority of which reside in the GI tract. Over the last few years the area of the microbiome and human health and disease has been an area of intense research interest. We know the organisms inhabiting our gut help us (the human host) in many ways: immune response, metabolism, energy harvest, and vitamin production are just a few examples. We also know that these microorganisms interact with each other, and with their human host in very complex ways. 
Kostic and colleagues provide us with the largest longitudinal study to date of the human microbiome. The authors performed microbial analysis on serial stool samples of infants genetically predisposed to develop type 1 diabetes and compared the results to stool samples from infants who did not possess genetic risk. Thirty-three children were followed for the first 3 years of life. Of these, 11 developed antibodies associated with type 1 diabetes, and of these, four developed clinical diabetes during the study period. The authors note that in the infants who develop diabetes, there is 25% drop in the number of distinct microbial species present in their microbiome. In fact, this reduction is seen up to 1 year prior to the development of diabetes.

This manuscript raises an interesting question: What, in fact, constitutes a healthy human GI microbiome? The short answer is: At this time, no one knows. What is known is that two major hallmarks that have been shown to be important in GI microbial “wellness” are redundancy and diversity. In fact, a decrease in both these qualities has been linked to other diseases, such as inflammatory bowel disease, obesity and type 2 diabetes. Based on this current paper, this concept seems to hold true for type 1 diabetes as well.
These data are provocative and interesting, and allow for the possibilities of therapeutic interventions by altering gut flora in a more “beneficial” fashion. While a fascinating concept, we are a long way from developing “designer microbes.” First, we need to get to know our microbes a little better and understand the mechanisms by which they interplay with each other as well as with their human host.


Ruchi Mathur, MD, FRCPC
Associate Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center
Medical Director, Diabetes Outpatient Treatment and Education Center
Assistant Program Director, Clinical and Translational Research Center

Disclosure: Mathur reports no relevant financial disclosures.