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Antibiotics, diabetes and the microbiome
The gut microbiome, comprised of millions of bacteria, has become an area of key interest in recent years due to its role in everything from basic health to gastrointestinal disorders. One of the latest disease areas the microbiome has been explored in is diabetes, specifically type 1 diabetes. In a study led by a team from NYU Langone Medical Center, researchers found that, at least in mice, antibiotics can alter the microbiome to the point that it can increase the risk for type 1 diabetes. The work was published in Nature Microbiology in an article titled “Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.”
As noted in the abstract of that paper, “The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease.” Type 1 diabetes is typified by the immune system attacking the islet cells in the pancreas that produce insulin, which in turn results in the body's inability to control and maintain normal blood glucose levels. It is thought that microbiomes play a role in teaching young immune systems to be less sensitive and therefore less inclined to attack themselves, and antibiotics could interrupt that.
And “early-life antibiotic use” isn't minimal these days; according to an NYU Langone Medical Center press release, an average American child gets 10 courses of antibiotics by the age of 10.
The mice used in this work were non-obese diabetic (NOD) mice, which are more prone to developing type 1 diabetes. The mice were exposed to either continuous low doses of antibiotics or pulsed antibiotic therapy (PAT), which is similar to the doses often used to treat infections in children.
What they found was that male NOD mice that underwent PAT had more than twice the incidence of type 1 diabetes—53 percent—as control NOD mice that did not receive antibiotics (26 percent). Interestingly, PAT didn't significantly increase disease risk in female mice in one set of experiments, but did increase risk in a second set.
“This latest study result is compelling, linking the effects of use of antibiotics in mice to type 1 diabetes,” says Jessica Dunne, director of discovery research at the Juvenile Diabetes Research Foundation. “This is the first study of its kind suggesting that antibiotic use can alter the microbiota and have lasting effects on immunological and metabolic development, resulting in autoimmunity. We’re eager to see how these findings may impact the discovery of type 1 diabetes preventive treatments in the future and continued research in the area of vaccines.”
In addition, samples of gut bacteria were collected from the mice and analyzed genomically and statistically. Three-week-old males that underwent PAT saw almost a complete loss in their intestines of certain bacteria that previous studies have tagged as playing a role in training the immune system. At all times in every sample, bacterial species diversity in the microbiomes of PAT-treated animals was lower than in the control mice, with differing composition as well. PAT mice were also found to have lower proportions of the regulatory T cells that restrain immune reactions.
When the team tried transferring gut bacteria from antibiotic-treated (perturbed) mice to germ-free mice—which lack their own microbiomes, they found that the perturbed microbial population was capable of altering the recipient’s immune system.
“PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression” as well, according to the abstract, which went on to state that “These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.”
According to the American Diabetes Association, 29.1 million people had diabetes in 2012 in the U.S. alone, and some 1.25 million children and adults in the country have type 1 diabetes.
This work was funded by the Juvenile Diabetes Research Foundation, the Diane Belfer Program for Human Microbial Ecology, the Howard Hughes Medical Institute, the Defendi Fellowship, the Knapp Family, the Ziff Family and C&D Funds. It was also partially supported by Cancer Center Support Grant P30CA016087 from the Laura and Isaac Perlmutter Cancer Center at NYU Langone.