To the Editor The study by Dr Beyerlein and colleagues1 is subject to an important confounder that challenges the validity of the association between infections and T1D. The prior administration of antibiotics has been strongly linked with the development of T1D both in empirical animal studies and in epidemiological studies.2,3 The gut microbiota is thought to be critical to the development of the immune system. Eradication or depletion of the gut fauna adversely affects this process, increasing the risk of autoimmunity possibly by inducing anergy in pathways involved in self-tolerance.2,3 Empirical animal models suggest that antibiotics in childhood, rather than infections, increase the risk of T1D.2,3 The antibiotic model also would explain the precipitous rise in incidence of T1D over the past decades, at a mean annual rate of 3% as reported by the World Health Organization.4 The misuse of antibiotics is an increasing global problem, with antibiotics administered inappropriately in viral infections.5A dose-response correlation is observed, whereby the greater the number of courses of antibiotics the greater the risk of T1D. Empirical and epidemiological studies both point to antimicrobials against gram-positive organisms as those most strongly associated with T1D.2 A definitive interpretation of the study by Beyerlein and colleagues is difficult without adjusting for this confounder.
Uzoigwe OF. Association of Infection in Early Life and Risk of Developing Type 1 Diabetes. JAMA. 2016;316(8):882-883. doi:10.1001/jama.2016.10291