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Discovery and Characterization of Bile Acid and Steroid Metabolism Pathways in Gut-Associated Microbes.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Discovery and Characterization of Bile Acid and Steroid Metabolism Pathways in Gut-Associated Microbes./
Author:	Harris, Spencer C.
Description:	1 online resource (259 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 78-09(E), Section: B.
Contained By:	Dissertation Abstracts International78-09B(E).
Subject:	Microbiology. -
Online resource:	click for full text (PQDT)
ISBN:	9781369745108

Discovery and Characterization of Bile Acid and Steroid Metabolism Pathways in Gut-Associated Microbes.
Harris, Spencer C.

Discovery and Characterization of Bile Acid and Steroid Metabolism Pathways in Gut-Associated Microbes. - 1 online resource (259 pages)

Source: Dissertation Abstracts International, Volume: 78-09(E), Section: B.

Thesis (Ph.D.)--Virginia Commonwealth University, 2017.

Includes bibliographical references

The human gut microbiome is a complex microbial ecosystem residing in the lumen of our gastrointestinal tract. The type and amounts of microbes present in this ecosystem varies based on numerous factors, including host genetics, diet, and environmental factors. The human gut microbiome plays an important role in normal host physiological functions, including providing energy to colonocytes in the form of short-chain fatty acids. However, gut microbial metabolites have also been associated with numerous disease states. Current tools for analyzing the gut microbiome, such as high-throughput sequencing techniques, are limited in their predictive ability. Additionally, "-omic" approaches of studying the complex array of molecules, such as transcriptomics (RNA), proteomics (proteins), and metabolomics (previously identified physiologically active molecules), give important insight as to the levels of these molecules but do not provide adequate explanations for their production in a complex environment. With a better physiological understanding of why specific metabolites are produced by the gut microbiome, more directed therapies could be developed to target their production. Therefore, it is immensely important to study the specific bacteria that reside within the gut microbiome to gain a better understanding of how their metabolic actions might impact the host. Within this framework, this study aimed to better understand the production of secondary bile acid metabolites by bacterial in the gut microbiome. High levels of secondary bile acids are associated with numerous pathophysiological disorders including colon cancer, liver cancer, and cholesterol gallstone disease. In the current study, three bile acid metabolizing strains of bacteria that are known members of the gut microbiome were studied. A novel strain of Eggerthella lenta was identified and characterized, along with the type strain, for its ability to modulate bile acid and steroid metabolism based on the atmospheric gas composition. Additionally, it was shown that the oxidation of hydroxyl groups on primary bile acids by E. lenta C592 inhibited subsequent 7alpha-dehydroxylation by Clostridium scindens . The gene involved in the production of a Delta4,6-reductase enzyme, responsible for catalyzing two of the final reductive steps in the 7alpha-dehydroxylation pathway, was putatively identified and characterized in Clostridium scindens ATCC 35704. Lastly, the transcriptomic profile of Clostridium scindens VPI 12708 in the presence of numerous bile acids and steroid molecules was studied. These studies contribute significantly to the understanding of why specific bile acid metabolites are made by members of the gut microbiome and suggest ways of modulating their production.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781369745108Subjects--Topical Terms:

591510
Microbiology.
Index Terms--Genre/Form:

554714
Electronic books.

Discovery and Characterization of Bile Acid and Steroid Metabolism Pathways in Gut-Associated Microbes.
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504 $a Includes bibliographical references
520 $a The human gut microbiome is a complex microbial ecosystem residing in the lumen of our gastrointestinal tract. The type and amounts of microbes present in this ecosystem varies based on numerous factors, including host genetics, diet, and environmental factors. The human gut microbiome plays an important role in normal host physiological functions, including providing energy to colonocytes in the form of short-chain fatty acids. However, gut microbial metabolites have also been associated with numerous disease states. Current tools for analyzing the gut microbiome, such as high-throughput sequencing techniques, are limited in their predictive ability. Additionally, "-omic" approaches of studying the complex array of molecules, such as transcriptomics (RNA), proteomics (proteins), and metabolomics (previously identified physiologically active molecules), give important insight as to the levels of these molecules but do not provide adequate explanations for their production in a complex environment. With a better physiological understanding of why specific metabolites are produced by the gut microbiome, more directed therapies could be developed to target their production. Therefore, it is immensely important to study the specific bacteria that reside within the gut microbiome to gain a better understanding of how their metabolic actions might impact the host. Within this framework, this study aimed to better understand the production of secondary bile acid metabolites by bacterial in the gut microbiome. High levels of secondary bile acids are associated with numerous pathophysiological disorders including colon cancer, liver cancer, and cholesterol gallstone disease. In the current study, three bile acid metabolizing strains of bacteria that are known members of the gut microbiome were studied. A novel strain of Eggerthella lenta was identified and characterized, along with the type strain, for its ability to modulate bile acid and steroid metabolism based on the atmospheric gas composition. Additionally, it was shown that the oxidation of hydroxyl groups on primary bile acids by E. lenta C592 inhibited subsequent 7alpha-dehydroxylation by Clostridium scindens . The gene involved in the production of a Delta4,6-reductase enzyme, responsible for catalyzing two of the final reductive steps in the 7alpha-dehydroxylation pathway, was putatively identified and characterized in Clostridium scindens ATCC 35704. Lastly, the transcriptomic profile of Clostridium scindens VPI 12708 in the presence of numerous bile acids and steroid molecules was studied. These studies contribute significantly to the understanding of why specific bile acid metabolites are made by members of the gut microbiome and suggest ways of modulating their production.
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