Changes in fecal microbiota after therapeutic exposure to amoxicillin-clavulanic acid in veal calves receiving multiple antibiotics

Amoxicillin-clavulanic acid (AMC) is an important antibiotic in human and veterinary medicine. However, it can select antibiotic-resistant bacteria in the gut microbiota and alter its composition. In calves, AMC can be used to treat complicated infections. The impact of AMC on the calves' gut is unknown; thus, we analyzed the effect of a five-day AMC treatment in veal calves suffering from omphalitis. AMC-treated calves (<i>n</i> = 15) and a control untreated group (<i>n</i> = 15) were enrolled from two farms. Stools were collected before AMC administration (D0), one day (D6), one month (D35), and two months (D55) after AMC withdrawal. The effect of AMC treatment on gut microbiota composition and resistance gene selection was analyzed by full-length 16S rRNA operon sequencing and qPCR, respectively. Selection of Extended-Spectrum Cephalosporin-Resistant (ESC-R) <i>Escherichia coli</i> in calf's fecal samples and dissemination in the farms' environment were analyzed by cultivation and genome sequencing of isolates. After AMC treatment, alpha-diversity decreased in AMC-treated calves along with a decrease of the relative abundance of bacterial families beneficial for host health (Lachnospiraceae) and an increase of Pseudomonadota, grouping opportunistic pathogens. ESC-R <i>E. coli</i> carriage dynamics were different between calves sampled from each farm and seemed independent from AMC treatment. Besides, calves received other antibiotics that could have an impact on resistance selection. Certain clones of ESC-R <i>E. coli</i> demonstrated a widespread dissemination in the farm, both in calves hosted in distant zones and in their environment. To decrease the antibiotic resistance burden, it is essential to use antibiotics judiciously, alongside improving hygienic practices in farms.<b>IMPORTANCE</b>Antibiotic therapies can select resistant bacteria in the gut of treated hosts and deplete bacteria that are beneficial to the host health. Antibiotic-resistant bacteria selected in the gut of food-producing animals, like veal calves, are excreted and can then disseminate among animals, to the environment (through manure or water contamination) and to farmers who may further disseminate these organisms to other people in contact. Antibiotic resistance genes can disseminate among clones present in the gut of both animal and human hosts by horizontal gene transfer. Studying the impact of antibiotic therapies on the gut microbiota has One Health relevance. Thus, we aimed to (i) analyze the impact of AMC treatment on the selection of resistant bacteria in the calf gut and its composition and (ii) analyze the dissemination resistance in farms in order to advise on potential strategies to counteract further spread of these microorganisms.