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Title: Exploring the impact of gastrointestinal parasitic helminths on the human microbiome using advanced biomolecular and bioinformatics technologies
Author: Jenkins, Timothy Patrick
ISNI:       0000 0004 7972 8984
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2019
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Our understanding of the biology of human gastrointestinal (GI) parasitic helminths is greater than ever before. However, so far, the research has focused on gene expression profiling, immune- and protein-protein interactions in host-parasite systems. The importance of parasite microbiota interactions has, so far, been largely overlooked. The microbiome is key to host health and it has been demonstrated that the balance between the gut microbiota and the host is crucial for health maintenance and that a disturbance of this balance can result in a range of diseases. Hence, given that GI nematodes and the gut microbiota share the same ecological niche within the human host, it is plausible that GI helminths and the host microbiota interact, and that this could significantly impact on the health and homeostasis of the parasite-infected hosts. Fortunately, the availability and affordability of next generation sequencing now enables us to investigate such host-parasite-microbiota interactions in depth and at high throughput. Therefore, the aims of this thesis were to explore the impact of such helminth infections in various systems, ranging from natural multi-species infections in a developing country to highly controlled and experimental infections involving a single species of parasitic helminth. This would allow the identification of microbiome changes that are consistent across different settings, as well as help detect alterations that are specific to a certain host-helminth system. Thus, the main aims of the thesis were: (i) to investigate the consequences of natural multi- or mono-species infections by helminth parasites on the composition of the human gut microbiota (Chapters 2 and 3), (ii) to elucidate the longitudinal impact of experimentally controlled monospecies helminth infections on the human gut microbiota (Chapter 4), (iii) and to examine whether an extra-intestinal (EI) helminth infection has an impact on the host microbiome in a murine model of human schistosomiasis (Chapter 5). Overall, I found that GI and EI helminths have a substantial impact on the host gut microbiota, both on individual taxa and on a community level. Many of the observed changes appeared to be specific to the host-helminth system that was being investigated, yet some consistencies emerged. Firstly, low level, long term, and single species infections that were not accompanied by pathology appeared to increase the gut microbial diversity within their host and promote a stable and healthy gut microbial composition (Chapters 3 and 4). Contrarily, acute heavy burden infections, associated with pathology, appeared to have the opposite effect, i.e. reducing the overall diversity of the host's gut microbiome and promoting the proliferation of opportunistic pathogens (Chapters 2 and 5). This suggests that parasitic helminth infections could detrimentally impact the hosts they infect besides the direct pathology they induce, but also adds further weight to the idea of a therapeutic use of helminths in the context of helminth therapy. Indeed, the beneficial effect helminths can have on the host gut microbiota, together with the mounting evidence towards an intrinsic link between autoimmune diseases and the microbiome, might present a mechanism through which helminths could exert a therapeutic effect on patients suffering from such conditions. In, conclusion the present thesis has contributed significantly by providing entirely new insights into the impact of natural and experimental parasitic helminth infections on the human gut microbiome (Chapter 6). The findings provide a sound basis for future fundamental investigations of, for example, the relationship of helminth species, abundance, and host to microbiome changes in the context of infection. However, the results also act as a stepping stone for studies exploring the translational potential of helminth-microbiota interactions, such as the role that helminth induced microbiome modulations play in infection pathology, or whether such changes play a key role in the therapeutic potential of helminth therapy.
Supervisor: Cantacessi, Cinzia Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
Keywords: Microbiome ; Parasite ; Gut ; Helminth ; NGS ; Bacteria ; Bioinformatics