The Human Gut Microbiome in the Context of Disease and Disruption

Rowan-Nash, Aislinn Danielle

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Year:: 2019
Contributor:: Rowan-Nash, Aislinn Danielle (creator); de Graffenried, Christopher (Reader); Vaishnava, Shipra (Reader); Weinreich, Daniel (Reader); Bucci, Vanni (Reader); Belenky, Peter (Advisor); Brown University. Biology and Medicine: Pathobiology (sponsor)
Genre:: theses
Subject:: microbiome; 16S rRNA Amplicon Sequencing; major depressive disorder; urogenital schistosomiasis; advanced dementia; shotgun metagenomics; antimicrobial resistance; gut microbiome
Extent:: xx, 238 p.

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Abstract:: In recent years, it has become increasingly appreciated that the human microbiome plays an important role in health and disease. Optimally, the gut microbiota contributes to digestion, immune regulation, and general gastrointestinal health. When dysregulated or disrupted, however, the gut microbiota has been implicated in a number of disease states, including infectious disease, autoimmune disorders, and even mental health conditions. We have examined the composition and predicted function of the gut microbiota associated with several disease states and potential microbiome disruptions in human subjects. First, we found that the gut microbiome was significantly different between Nigerian adolescents infected with the bloodstream helminth Schistosoma haematobium and their uninfected peers, with signatures of potential gastrointestinal dysbiosis associated with infection despite the parasite’s location in the vasculature of the urogenital system. Second, we found differences in the gut microbiota of young adults with major depressive disorder (MDD), particularly a reduction in the relative abundance of the genus Faecalibacterium and an increase in the abundance of the genus Flavonifractor in subjects with MDD. As Faecalibacterium has been associated with anti-inflammatory effects and Flavonifractor has been previously associated with a number of inflammatory and psychiatric disorders, this may support research suggesting that MDD is associated with chronic low-grade inflammation. Finally, we found that the gut microbiota of institutionalized elderly patients with advanced dementia was temporally unstable and not significantly impacted by administration of the fluoroquinolone levofloxacin. However, we did find that the level of antibiotic resistance genes (ARGs) in the samples could be predicted by the relative abundance of the three potential pathogens Escherichia coli, Proteus mirabilis, and Enterococcus faecalis, and metagenomic assembly and binning revealed that these species tended to have higher levels of ARGs than other abundant microbiota members. Together, these studies highlight the important role of the gut microbiota as potential contributors to or markers of non-gastrointestinal diseases and as reservoirs of ARGs in the human host.
Notes:: Thesis (Ph. D.)--Brown University, 2019

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Rights: In Copyright
Restrictions on Use: Collection is open for research.

Citation

Rowan-Nash, Aislinn Danielle, "The Human Gut Microbiome in the Context of Disease and Disruption" (2019). Pathobiology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:1129453/

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Pathobiology Theses and Dissertations

Theses and Dissertations for the Pathobiology department.
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