The infant gut microbiome and resistome in health and disease

Abstract

In this thesis, we describe the development of the infant gut microbiome and resistome, identify important environmental and nutritional drivers of this development and study the gut microbiome and microbial networks in relation to health and disease. We have shown that mode of delivery impacts the composition of the gut microbiome, with infants born by caesarean section carrying a higher abundance of potential pathogens such as Klebsiella and Enterococcus species in their gut. Interestingly, we could associate an increased abundance of these gut bacteria at one week of life with a higher susceptibility to respiratory tract infections in the first year of life. Next, we have established that even a short course of early-life broad-spectrum antibiotics has long-term effects on the developing infant gut microbiome, especially selecting for potential pathogenic bacteria and increasing the abundance of antimicrobial resistance genes for a prolonged period of time. In case of suspected early-life infection, we strongly advise treatment with the antibiotic combination consisting of penicillin + gentamicin, as this has the least detrimental impact on microbiome and resistome development, when compared to the commonly used combinations co-amoxiclav + gentamicin or amoxicillin + cefotaxime. Finally, we modelled microbial networks across body sites, spanning the gut and respiratory tract, and found that infants with less robust networks had a higher susceptibility to respiratory tract infections. Altogether, the results of this thesis provide insights into multiple environmental drivers of the infant gut microbiome and resistome development and how these relate to health later in life.