"Antibiotics remain valuable agents to fight infectious disease, but can also affect the normal gastrointestinal tract (GIT) microbiota resulting in detrimental symptoms. Despite the long therapeutic use of antibiotics, it is still unclear which components of the anaerobic gut microbiota are affected causing the development of antibiotic-associated diarrhoea (AAD), one of the most frequent side effects of antibiotic intake. It is also unknown whether the reduced number of commensal bacteria is sufficient to favour pathogen colonization, including by the most pathogenic agent linked to AAD, Clostridium difficile, or whether other conditions in the GIT change to promote pathogen colonization. The objectives of this proposal are (1) to rapidly monitor variations in the structure of the colonic microbial community thus identifying any population shifts due to tetracycline (Tc) therapy in human acne sufferers, (2) to investigate the effect of Tc treatment and other gut parameters on specific gene expression and the colonization ability of C. difficile isolates, and (3) to monitor changes in the occurrence and prevalence of specific tetracycline resistance (TcR) genes following long-term Tc treatment. The combination of the molecular ecology, molecular genetics and transcriptomic approaches that will be applied in this proposal will provide us with a deeper understanding of the role played by the GIT microbiota in human health, including how pathogens may gain control of the GIT ecosystem following antibiotic therapy, and finally of the contribution made by commensal GIT bacteria to the dissemination and emergence of bacterial antibiotic resistance."