Exploring the mycobiota for the treatment of gut-related diseases
Typ
Examensarbete för masterexamen
Program
Biotechnology (MPBIO), MSc
Publicerad
2020
Författare
Clausen Lind, Andrea
Modellbyggare
Tidskriftstitel
ISSN
Volymtitel
Utgivare
Sammanfattning
Our gut harbors trillions of microorganisms that form a bridge between our diet and whole-body metabolism. This collection of microorganisms, referred to as the gut microbiota, can in some cases be perturbed and lead to the onset of disease. Studies exploring the gut microbiota have identified a plethora of bacteria implicated in multiple diseases; however, the fungal component of the microbiome, known as the mycobiome, remains largely unexplored. Similarly, engineered live biotherapeutics designed to target these diseases have mainly been limited to bacterial chassis. This makes the mycobiome a promising target for exploratory and therapeutic efforts in the understanding and management of gut related diseases. Herein, we aimed to engineer the probiotic yeast Saccharomyces boulardii as a live biotherapeutic for treatment of the inborn metabolic disease phenylketonuria by making the yeast consume large amounts of phenylalanine. An improved consumption of phenylalanine was observed in several of the resulting stains compared to control strains, but the overall consumption was still far from what would be required for effective treatment of the disease. As an offshoot of this project, we also aimed to develop and apply an effective platform for analysis of the fungal composition in metagenomic data. This was achieved by modifying an existing fungal metagenomics pipeline and subsequently analyzing the mycobiome of ~1300 fecal samples from patients with Inflammatory Bowel Disease (IBD), obtained from the integrative Human Microbiome Project data set. Several fungi were found to be slightly but significantly enriched in IBD patients compared to healthy controls. Furthermore, some of the identified fungi have been identified in previous studies of the mycobiome in IBD, validating our approach. In summary, this thesis highlights the unexplored potential of the human gut mycobiome across diseases.
Beskrivning
Ämne/nyckelord
Yeast Probiotics , Live biotherapeutics , Phenylketonuria , Mycobiome , Metagenomic analysis , Inflammatory Bowel Disease