The preterm gut microbiome in health and disease – metagenomic approaches for microbial diagnostics

Alcon, Cristina (2019) The preterm gut microbiome in health and disease – metagenomic approaches for microbial diagnostics. Doctoral thesis, University of East Anglia.

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Premature infants, born before 37 weeks of gestation, represent an important patient group at risk of developing numerous diseases such as necrotising enterocolitis and bacterial sepsis. This risk is correlated with changes in the preterm gut microbiome, which is influenced by multiple post-natal factors including gut immaturity, C-section delivery, exposure to antibiotics and difficulties in establishing breastfeeding. To reduce the risk of disease development in premature infants and reduce colonisation of bacterial pathogens, oral supplementation with beneficial bacteria including Lactobacillus and Bifidobacterium is used.

Before widespread uptake of this intervention, there is a pressing need to understand the impact of post-natal factors and how probiotic supplementation may modulate the preterm microbiome. In this thesis, I comprehensively examined the bacterial colonisation patterns of the preterm microbiome in health and disease using next-generation sequencing approaches. I also evaluated if probiotic supplementation can modify the gut microbiome in premature infants.

Short- and long-read metagenomics sequencing was used, complemented with culturing and phenotypic testing. A 16S rRNA microbiome profiling pipeline was optimised to characterise faecal samples from premature infants with and without probiotic supplementation. The methods developed provided the foundation for a large-scale clinical study (BAMBI) which sought to explore the impact of probiotic supplementation on the preterm gut microbiome in 233 infants. A subset of these faecal samples (96 samples) were examined using shotgun metagenomics to study the gut bacterial reservoir of antibiotic resistance genes (the ‘resistome’) after antibiotic treatment and to elucidate whether probiotic supplementation impacts the prevalence of AMR genes. Finally, MinION Nanopore sequencing was used to rapidly profile faecal samples from critically ill premature infants.

Overall, this multidisciplinary work provides novel insights into the preterm gut microbiome in health and disease, emphasises the protective role of probiotic supplementation when administered to premature infants, and evaluates whether rapid sequencing approaches can be applied for prompt microbial diagnostics.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Chris White
Date Deposited: 08 Feb 2021 15:23
Last Modified: 08 Feb 2021 15:23

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