Application of ‘-omics’ technologies for diagnosis and surveillance of gastrointestinal infections.

Neuert, Saskia (2020) Application of ‘-omics’ technologies for diagnosis and surveillance of gastrointestinal infections. Doctoral thesis, University of East Anglia.

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Abstract

The burden of gastrointestinal infections remains high, even in industrialised countries. Accurate, timely identification of enteropathogens is crucial for targeted treatment and global disease management. Routine diagnostic methods can be time-consuming, often rely on pathogen isolation prior to phenotypic characterisation, and still commonly fail to detect the aetiological agent. This thesis explores the use of ‘-omics’ technologies as an alternative to conventional diagnostic and surveillance approaches.

A supervised learning algorithm using taxonomic and metabolic gut microbiota profiles derived from 16S rRNA gene sequencing and 1H nuclear magnetic resonance spectroscopy of faeces from 41 controls and 246 gastroenteritis patients allowed distinction of bacterial and protozoal infections with a prediction accuracy of 81.61%.

Metagenomic sequencing of twenty Salmonella enterica-positive stool samples confirmed the presence of S. enterica in 70% of samples. Data was compared with whole genome sequences from the corresponding pathogen isolates. Metagenome coverage was insufficient for reconstruction of phylogenies and antimicrobial resistance profiling.

Comparison of antimicrobial resistance profiles inferred from whole genome sequences of 3,941 non-typhoidal S. enterica isolates with the results of phenotypic testing showed that resistance profiles encompassing fifteen antimicrobials were in complete agreement for 97.82% of isolates, with discordant results for only 0.17% of all possible isolate/antimicrobial combinations.

A longitudinal metagenomic study monitoring changes in the gut antimicrobial resistome in 48 travellers visiting regions with high prevalence of resistance revealed that travel led to a 1.27-fold increase in the number of antimicrobial resistance determinants and increased carriage of potentially pathogenic species in the cohort, with some changes persisting up to six months after return.

The results presented in this thesis provide evidence that some ‘–omics’-based approaches are suitable alternatives to traditional methods used for the diagnosis and surveillance of gastrointestinal infections, and that other tools could be of clinical use after further development work.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	20 Oct 2022 10:02
Last Modified:	20 Oct 2022 10:02
URI:	https://ueaeprints.uea.ac.uk/id/eprint/89235
DOI:

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