Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

The human body contains many microbes that play important roles in our health. These microbes begin to live in the intestines, skin, and mouth shortly after birth. They form complex communities called the microbiome, which changes as babies develop. The microbiome works with organs to maintain human health. For example, the lower intestinal tract is home to the most numerous and active microbes in the body. The intestines provide microbes with food and a welcoming environment, and the microbes make products the body needs, influence immune system development, and help maintain a balance of beneficial microbes. Use of antibiotics to treat infections, particularly early in life, disrupts intestinal microbe communities. Recent studies show that such microbiome disturbances may affect how the immune system develops and the rate at which type 1 diabetes develops. Type 1 diabetes is an autoimmune disease in which the immune system destroys cells in the pancreas that produce insulin. Scientists would like to learn more about how use of antibiotics in early life may contribute to the development of this disease. Now, Zhang et al. show that a single course of antibiotics administered early in life accelerates the development of type 1 diabetes in mice prone to develop the disease. In the experiments, a strain of laboratory mice that spontaneously develops type 1 diabetes were either given a single course of antibiotics, three courses of antibiotics, or no antibiotics in their first weeks of life. After one single course, the gut microbiome was different in mice treated with antibiotics compared with mice who were never exposed. The antibiotics also changed the molecules produced by these microbes. These alterations in the microbiome turned on or off certain genes in the intestine, affecting the development of the immune system. Zhang et al. identified some microbes that appear to protect against type 1 diabetes and others that seem to speed it up and how they do so. Antibiotic use in children is very common, so finding ways to reduce its potentially harmful effects on development are critical. The experiments provide one way to study how antibiotics may contribute to autoimmune disease. It also may allow scientists to test ways to reverse harmful change.