Abstracts Category : Other

Metagenomics profiling of the human gut microbiome in the context of faecal microbiota transplantation

by Simone Li

Public interest in faecal microbiota transplantation (FMT), which involves the transfer of a microbial community from healthy donor to patient, has increased greatly in recent years due to demonstrated potential in treating various chronic gastrointestinal disorders. However, the mechanisms underlying the clinical success of the therapy and its overall impact on the gut microbiome are still unclear. Recent developments in metagenomics have enabled better characterisation of gut microbial communities, primarily through DNA sequencing of faecal samples. However, changes in the microbiome of FMT recipients have to date been described at taxonomic resolutions up to species level only, and methodologies to systematically compare metagenomes have not been available. In this thesis, we developed a novel framework for the analysis of temporal metagenomics data at both species and strain level. Using approaches that accounted for putative species and strains (that is, those without characterised genomes), it provided increased resolution into the population structure of gut microbial communities. The detection of signatures based on single-nucleotide variants (SNV) in metagenomes, for example, enabled donor and recipient strain populations to be distinguished from each other, and their fate assessed through the profiling of post-FMT microbiomes. The methodologies were applied to a total of 273 stool metagenomes from healthy individuals and patients who received FMT treatment for metabolic syndrome, Clostridium difficile infection and ulcerative colitis. We demonstrate that donor strains can successfully and durably establish and, in some cases, completely replace native conspecific strains in the recipient. However, rather than one population dominating the other, we observed an extensive coexistence of donor and recipient strains across disease indications and irrespective of clinical outcome. Newly introduced strains were found to colonise more readily than foreign bacterial species, providing rationale for the use of strain-based therapeutics. Additionally, recipients with the same donor displayed varying degrees of microbiota transfer, indicating patterns of potential donor-recipient compatibilities. Our results thus provide ecological and mechanistic insights into FMT, as well as motivation for the development of personalised and more targeted microbiota-directed treatments.Advisors/Committee Members: Bork, Peer, Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany, Wilkins, Marc R, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.