Impact of antibiotics on the gut and milk microbiome

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Patangia, Dhrati
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University College Cork
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While antibiotics are lifesaving, they come at the cost of antimicrobial resistance (AMR) and collateral damage to microbiome. Using single-sample and longitudinal study designs, this thesis aimed to study antibiotic resistance genes (ARGs) spread using shotgun metagenomics sequencing. ARGs developed in animals can enter humans through the food chain. We examined the effect of single antibiotic use on microbiome and resistome in milk from dairy cows longitudinally. The microbial diversity increased from colostrum to later time-points in the antibiotic groups which was not prominent in the no-ab group. Further, microbial composition in all groups was different, leading to distinct clustering of no- antibiotic from antibiotic groups. All groups had a wide resistome profile, with antibiotic groups showing higher ARG abundance. Also, high abundance of mastitic pathogens was absent in the no-ab group. The results show that prophylactic antibiotics during DCT is not essential. We next longitudinally studied microbiome and resistome in infants divided into three groups [CSab (C-section/antibiotic), CSnoab (C-section/antibiotic naive) and VDnoab (Vaginal delivered/antibiotic naive)] based on delivery mode and antibiotic use during early life. CSab group showed low initial microbial diversity, which increased gradually and slowly. CSab group demonstrated significant associations to antibiotic classes corresponding to the antibiotic administered to infants in this group. Taxa belonging to Gammaproteobacteria were dominant carriers of ARGs, most being non persisters. The results show that early antibiotic exposure can have immediate and long-term effects on the infant microbiome. Next, publicly available shotgun-sequencing data was downloaded, analysed, resulting in a catalogue of early-life gut genomes of infants below three years of age which was used to study the global resistome. Gram-negative bacteria such as Escherichia, Enterobacter, Citrobacter, Klebsiella had highest ARG abundance with Glycopeptides, fluoroquinolone, macrolides, tetracyclines being most abundant classes. High abundance of ARGs was positively related to the socioeconomic status and healthcare access index of a country. These results confirm infant gut microbiota as ARG reservoir. Lastly, the gut microbial and resistome profile of adult cystic fibrosis (CF) patients was studied due to their chronic antibiotic use. The CF group had a microbial composition significantly distinct from controls with higher abundance of ARGs and virulence factors. CF group showed strong association to antibiotic classes administered to individuals in this group. Our results demonstrate the need to investigate the resistome and functional profile in this patient group; as antibiotic overuse can lead to MDR, aggravating the health status. This thesis sheds light on the microbial and resistome profile in previously unexplored manners and provides a baseline for researchers and policy makers to design pre-emptive and proactive measures to maximise health restoration and minimise ARG development.
Resistome , Infant gut resistome , Bovine milk resistome , Shotgun metagenomics sequencing , Microbiome
Patangia, D. 2023. Impact of antibiotics on the gut and milk microbiome. PhD Thesis, University College Cork.