GASTROENTEROLOGY • December 2013 EMJ EUROPEAN MEDICAL JOURNAL 74 EFFECTS OF ANTIBIOTIC USE ON THE MICROBIOTA OF THE GUT AND ASSOCIATED ALTERATIONS OF IMMUNITY AND METABOLISM M. Pilar Francino, 1,2 Andrés Moya 1,3 1. Senior Scientist, Joint Research Unit for Genomics and Health, Foundation for the Promotion of Health and Biomedical Research in Valencia (FISABIO-Public Health), Cavanilles Institute of Biodiversity and Evolutionary Biology, University of Valencia, Valencia, Spain 2. Adjunct Assistant Professor, School of Natural Sciences, University of California Merced, CA, USA 3. Senior Scientist, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Spain Disclosure: No potential confict of interest. Received: 30.10.13 Accepted: 20.11.13 Citation: EMJ Gastroenterol. 2013;1:74-80. ABSTRACT The excessively widespread use of antibiotics has created many threats. A well-known problem is the increasing bacterial resistance to antibiotics, which has clearly become a worldwide challenge to the efective control of infections by many pathogens. But, beyond afecting the pathogenic agents for which it is intended, antibiotic treatment also afects the mutualistic communities of microbes that inhabit the human body. As they inhibit susceptible organisms and select for resistant ones, antibiotics can have strong immediate efects on the composition of these communities, such as the proliferation of resistant opportunists that can cause accute disease. Furthermore, antibiotic-induced microbiota alterations are also likely to have more insidious efects on long-term health. In the case of the gut microbiota, this community interacts with many crucial aspects of human biology, including the regulation of immune and metabolic homeostasis, in the gut and beyond. It follows that antibiotic treatments bear the risk of altering these basic equilibria. Here, we review the growing literature on the efects of antibiotic use on gut microbiota composition and function, and their consequences for immunity, metabolism, and health. Keywords: Antibiotics, human microbiome, gut microbiota, pathogenic bacteria, infection, immunity, autoimmunity, immunotolerance, atopy, infammation, metabolism, obesity, metabolic syndrome. INTRODUCTION The gut harbours the most dense and complex microbiota of the human body, which contributes importantly to several basic physiological functions, including nutrition, defence against pathogens, and metabolic and immune homeostasis. Consequently, disturbances in the composition and function of the gut microbiota, i.e. dysbioses, can have severe consequences for health at several diferent levels. 1,2 In particular, evidence is mounting for the involvement of dysbioses in the broad variety of health problems associated to immune and metabolic malfunctions. Antibiotics are one of the main factors causing dysbiosis and therefore play a signifcant role in generating the associated suite of undesirable health efects. In this review, we will frst address the direct efects of antibiotics on the gut microbiota, and we will then discuss how antibiotic-induced dysbioses relate to immune and metabolic health, and the underlying mechanisms likely to be responsible for such relationships. EFFECTS OF ANTIBIOTICS ON THE GUT MICROBIOTA Numerous works employing diferent technologies have explored the efects of antibiotics on the