Over the past decades, antibiotic-resistant bacteria have become increasingly prevalent, posing a significant threat to public health. Although classic risk factors are well-established, the potential risk associated with proton pump inhibitors has received little attention, despite the long-standing theory that the acidity of the stomach is a first line of defense of the host against enteric bacterial disease. In part I of this thesis we investigate the role of gastric acid suppression as a risk factor for the acquisition of multidrug-resistant micro-organisms, with a focus on (extended spectrum beta-lactamases) ESBL-producing Enterobacterales. In addition, in part II of this thesis, we (1) aimed to determine the risk of infection in patients colonized with multidrug-resistant bacteria and (2) studied the composition of the microbiota and associated metabolome in carriers and non-carriers of ESBL-producing E. coli.