Bacteriophages – A key component in shaping a healthy gut microbiome

Research output: Book/ReportPh.D. thesisResearch

During the last decade it has become evident that the gut microbiome (GM) strongly influences human health and disease, since GM imbalances (dysbiosis) have been associated with various diseases like obesity, type-2-diabetes mellitus (T2DM), and recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggest that the viral community of the GM, predominated by bacteriophages (phages), plays a pivotal role in shaping the GM component. Phages are viruses that infect and attack bacteria in a host-specific manner. The bacteria and phages coexists through an arms race where bacteria activate defence systems that the phages seek to circumvent by various strategies. Phages impact on the GM component was emphasised by a recent pilot study that demonstrated how rCDI patients were successfully treated by transferring sterile filtrated faeces (containing phages, but no intact bacterial cells) from a healthy donor. An approach we will refer to as faecal virome transplantation (FVT) which we believe have a therapeutic potential to restore a GM in dysbiosis. During the course of the PhD project we discovered a novel spore forming gut bacterium that represented a novel genus and species. Furthermore, we investigated the co-evolution of the adaptive immune system (CRISPR-Cas) of the prevalent gut bacterium Eggerthella lenta and its antagonist phage, to increase the understanding of the complex interactions between bacteria and phages in the gut. We characterised the bacterial and viral gut community in the same mouse strain from different vendors, since divergences in the GM component potentially yield contradictive results in animal models. We thereby highlighted the importance of considering the impact of the GM composition prior animal studies. Intriguingly, we showed how FVT to dietinduced obese mice could alleviate the symptoms of obesity and T2DM while manipulating the GM component. The FVT treated mice decreased in weight gain compared to non-treated mice and exhibited a completely normalised blood sugar tolerance compared to lean controls. Although the concept of FVT is at its infancy we collected the few published FVT studies in a review manuscript and analysed the available experimental data that might explain the underlying mechanisms of the complex interactions between phages, bacteria, and the host. We hypothesise that the introduction of the viral community by FVT initiates cascading events that shift the GM composition into a more stable state, which ultimately improves the host phenotype.
Original languageEnglish
PublisherDepartment of Food Science, Faculty of Science, University of Copenhagen
Number of pages221
Publication statusPublished - 2020

ID: 244526049