Interplay between gut microbiota and antibiotics

Abstract

The human body is colonized by a vast number of microorganisms collectively defined as the microbiota. In the gut, the microbiota has important roles in health and disease, and can serve as a host of antibiotic resistance genes. Disturbances in the ecological balance, e.g. by antibiotics, can affect the diversity and dynamics of the microbiota. The extent of the disturbance induced by antibiotics is influenced by, among other factors, the class of antibiotic, the dose, and administration route. One of the most common consequences of excessive antibiotic use is the emergence of antibiotic resistant bacteria and the dissemination of the corresponding resistance genes to other microbial inhabitants of the gut community, in addition to affecting the colonization resistance and promoting the overgrowth of pathogens. These effects are particularly relevant for Intensive Care Unit (ICU) patients, which are frequently exposed to a high risk of hospital-acquired infections associated with antibiotic resistant bacteria.Due to the important roles that members of the gut microbiota play in the host, including their role as potential hubs for the dissemination of antibiotic resistance, recent research has focused on determining the composition and function of gut microorganisms and the antibiotic resistance genes associated with them.The objectives of the research described in this thesis were to study the diversity and dynamics of the gut microbiota and resistome in ICU patients receiving antibiotic prophylactic therapy, and to assess the colonization dynamics with antibiotic resistant bacteria focusing on the commensal microbiota as a reservoir of antibiotic resistance genes by using culture dependent and independent techniques. Furthermore, the genetic background involved in the subsistence phenotype was investigated to disentangle the links between resistance and subsistence.Bacteria harbor antibiotic resistance genes that participate in a range of processes such as resisting the toxic effects of antibiotics, but could also aid in the utilization of antibiotics as sole carbon source, referred to as antibiotic subsistence phenotype.In chapter 2, the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics was investigated.Various gut isolates of Escherichia coli and Cellulosimicrobium spp. displayed the subsistence phenotype, mainly with aminoglycosides. Although no antibiotic degradation could be detected, the number of colony forming units increased during growth in medium with only the antibiotic as a carbon source. By using different approaches to study the aminoglycoside subsistence phenotype, we observed that laboratory strains carrying the aminoglycoside 3'phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides and that glycosylhydrolases seem to be involved in the subsistence phenotype. As the zoo animals for which the subsistence phenotype was investigated also included a number of nonhuman primates, the applicability of Human Intesti...