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• 41. [Article] Investigating the Role of Immunity and Other Selective Pressures on the Assembly of the Gut Microbiota in Zebrafish and Humans

  Over the past few decades, it has become increasingly apparent that host-associated microbial communities play an integral role in the development, physiology, and health of their host organisms. All hosts ...

  Citation × Citation Citation Abstract Copy Title: Investigating the Role of Immunity and Other Selective Pressures on the Assembly of the Gut Microbiota in Zebrafish and Humans Author: Stagaman, Keaton Year: 2016 Over the past few decades, it has become increasingly apparent that host-associated microbial communities play an integral role in the development, physiology, and health of their host organisms. All hosts have evolved mechanisms to filter the microbial taxa that comprise their resident intestinal microbial community, or gut microbiota. Utilizing the zebrafish as a model host organism, we documented the development of the gut microbiota through time, and found a significant shift in the composition of the gut microbiota after the onset of adaptive immunity. This led us to hypothesize that adaptive immunity is an important determinant of gut microbiota composition. We tested this hypothesis using wild type and rag1-/- zebrafish, which lack a functional adaptive immune system. Additionally we tested the robustness of the effects of adaptive immunity to dispersal of microbes between immune-compromised and immune-competent genotypes. We found that adaptive immunity had less of an effect on the composition of the gut microbiota than we expected, although there were intriguing differences in the nature of selection imposed when adaptive immunity was present than when it was absent. Because “westernization”, or market-integration, has been associated with significant changes in the human microbiota and certain health risks, we used similar analyses to those we applied to the zebrafish system to determine whether market-integration alters the filtering effects of inflammation and intestinal helminth parasites on the intestinal microbial community. We found that market-integration increased inter-subject dissimilarity and reduced inter-subject dispersal. Even small changes in the inflammation marker, CRP, were associated with differences in the gut microbiota, but these effects were reduced in the presence of helminth infection, which has been hypothesized to affect the microbiota by reducing inflammation. In total, this dissertation provides evidence for the nature and importance of host filters of the gut microbiota across two vertebrate species, as well as providing a framework for future studies of the effects of such filters on the assembly of the gut microbiota. This dissertation includes previously published, and unpublished, co-authored material. Title: Investigating the Role of Immunity and Other Selective Pressures on the Assembly of the Gut Microbiota in Zebrafish and Humans Author: Stagaman, Keaton Year: 2016 Over the past few decades, it has become increasingly apparent that host-associated microbial communities play an integral role in the development, physiology, and health of their host organisms. All hosts have evolved mechanisms to filter the microbial taxa that comprise their resident intestinal microbial community, or gut microbiota. Utilizing the zebrafish as a model host organism, we documented the development of the gut microbiota through time, and found a significant shift in the composition of the gut microbiota after the onset of adaptive immunity. This led us to hypothesize that adaptive immunity is an important determinant of gut microbiota composition. We tested this hypothesis using wild type and rag1-/- zebrafish, which lack a functional adaptive immune system. Additionally we tested the robustness of the effects of adaptive immunity to dispersal of microbes between immune-compromised and immune-competent genotypes. We found that adaptive immunity had less of an effect on the composition of the gut microbiota than we expected, although there were intriguing differences in the nature of selection imposed when adaptive immunity was present than when it was absent. Because “westernization”, or market-integration, has been associated with significant changes in the human microbiota and certain health risks, we used similar analyses to those we applied to the zebrafish system to determine whether market-integration alters the filtering effects of inflammation and intestinal helminth parasites on the intestinal microbial community. We found that market-integration increased inter-subject dissimilarity and reduced inter-subject dispersal. Even small changes in the inflammation marker, CRP, were associated with differences in the gut microbiota, but these effects were reduced in the presence of helminth infection, which has been hypothesized to affect the microbiota by reducing inflammation. In total, this dissertation provides evidence for the nature and importance of host filters of the gut microbiota across two vertebrate species, as well as providing a framework for future studies of the effects of such filters on the assembly of the gut microbiota. This dissertation includes previously published, and unpublished, co-authored material. Close