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Doctoral Thesis
Exploring the Functional Ecology of the Human Gut Microbiome Using In Vivo and In Vitro Models
Doctor of Philosophy (PhD), Murdoch University
2025
DOI:
https://doi.org/10.60867/00000061
Abstract
The evidence obtained during the last two decades has revealed the crucial role of the gut microbiome in human health. Disruptions in the composition and low diversity of the gut microbial community have been associated with various diseases, including inflammatory bowel conditions, diabetes, cancers and neurological disorders. Two key questions surround this research field: Who are the key microbes involved in these processes? And what are they doing? The microbiome research field has become dominated by nucleic-acid-based approaches that have provided valuable information on the functional potential of gut microbial communities. However, there is still a considerable gap in our understanding of the functional ecology of the gut ecosystem, because these approaches infer its functionality but do not measure it directly. This thesis contributes to filling this gap by exploring the relationship between microbiota composition and metabolic function using different in vivo and in vitro models, including human cohort studies, bioreactors, phenotypic arrays, and faecal cultures. A combination of 16S rRNA amplicon gene sequencing, along with High-Performance Liquid Chromatography Mass Spectrometry (HPLC-MS) and Nuclear Magnetic Resonance (NMR) spectroscopy, was used to characterise the microbiota composition and metabolic profiles of samples obtained from these models, which included human serum, urine, faeces, and faecal culture samples. The main findings of this thesis can be summarised in 3 key points: (i) faecal cultures can uncover features of the gut microbial ecology that are not apparent in the direct analysis of faecal samples. (ii) There is a degree of discrepancy between what would be expected from microbiota composition analyses and the actual metabolic output of the community. In other words, two communities with distinct taxonomic compositions can exhibit similar metabolic profiles and vice versa. (iii) Antimicrobials can induce a phenomenon of metabolic phenoconvergence, in which microbial communities with distinct taxonomic communities are pushed towards similar metabolic outputs. This thesis highlights the potential of integrative approaches using in vitro models, sequencing technologies, and metabolic profiling to provide insights into the functional ecology of the human gut microbiome and its potential impact on the human host.
Details
- Title
- Exploring the Functional Ecology of the Human Gut Microbiome Using In Vivo and In Vitro Models
- Authors/Creators
- David F Garcia Mendez
- Contributors
- Elaine Holmes (Supervisor) - Murdoch University, Centre for Computational and Systems MedicineJaneth Sanabria (Supervisor) - Murdoch UniversityJulien Wist (Supervisor) - Murdoch University, Centre for Computational and Systems Medicine
- Awarding Institution
- Murdoch University; Doctor of Philosophy (PhD)
- Identifiers
- 991005852588507891
- Murdoch Affiliation
- Centre for Computational and Systems Medicine
- Resource Type
- Doctoral Thesis
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