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Host-Pathogen-Gut Microbiota Interactions: The Role of Diet, Microbiota Metabolites, and the Aryl Hydrocarbon Receptor in Survival From Sepsis and Surgical Injury /

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Host-Pathogen-Gut Microbiota Interactions: The Role of Diet, Microbiota Metabolites, and the Aryl Hydrocarbon Receptor in Survival From Sepsis and Surgical Injury // Robert Charles Keskey.
作者:	Keskey, Robert Charles,
面頁冊數:	1 electronic resource (205 pages)
附註:	Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
提要註:	Host-microbiota-pathogen interactions play a key role in determining survival from lethal bacterial infection leading to sepsis. Here we demonstrate that western diet, high in fat and low in fiber, increases the risk for pathogen colonization in the gut and results in gut-derived sepsis when mice are exposed to antibiotics, starvation, and surgical injury. The risk of postoperative sepsis in various surgical mouse models can be mitigated through dietary prehabilitation with a diet low in fat and high in fiber. Dietary prehab provides protection, in part, once the functional production of butyrate is restored. Furthermore, pathogen colonization and susceptibility can be mitigated with a diet high in fiber which increases microbiota resiliency by inducing production of the quorum sensing molecule AI-2 which stabilizes Firmicutes in the face of antibiotic exposure. The western diet alterations not only destabilize metabolite production of the gut microbiota, but also increase the presence of antibiotic resistance genes independent of antibiotic exposure conferring resistance to macrolides, fluoroquinolones, and cephalosporins. Gut-derived metabolites such as indoles were found to drive a recovery directed immune response in mice exposed to lethal bacterial peritonitis. During lethal infection, indole metabolites enhanced survival by activating AhR on macrophages which increased bacterial clearance and induce resolution of inflammation. Oral supplementation with tryptophan or direct injection of indole metabolites improved survival in this model. To further implicate the importance of indole activation of AhR, select bacterial pathogens actively inhibited indole activation of AhR via the secretion of small molecules such as enterobactin. Finally, indole metabolites in the gut of septic patients correlated with survival. In conclusion, the structure and function of the gut microbiota is influenced by diet and has major downstream implications on pathogen colonization, virulence expression and survival from a lethal bacterial infection such as murine peritonitis.
Contained By:	Dissertations Abstracts International85-12B.
標題:	Surgery. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31148215
ISBN:	9798382782638

Host-Pathogen-Gut Microbiota Interactions: The Role of Diet, Microbiota Metabolites, and the Aryl Hydrocarbon Receptor in Survival From Sepsis and Surgical Injury /
Keskey, Robert Charles,

Host-Pathogen-Gut Microbiota Interactions: The Role of Diet, Microbiota Metabolites, and the Aryl Hydrocarbon Receptor in Survival From Sepsis and Surgical Injury /Robert Charles Keskey. - 1 electronic resource (205 pages)

Source: Dissertations Abstracts International, Volume: 85-12, Section: B.

Host-microbiota-pathogen interactions play a key role in determining survival from lethal bacterial infection leading to sepsis. Here we demonstrate that western diet, high in fat and low in fiber, increases the risk for pathogen colonization in the gut and results in gut-derived sepsis when mice are exposed to antibiotics, starvation, and surgical injury. The risk of postoperative sepsis in various surgical mouse models can be mitigated through dietary prehabilitation with a diet low in fat and high in fiber. Dietary prehab provides protection, in part, once the functional production of butyrate is restored. Furthermore, pathogen colonization and susceptibility can be mitigated with a diet high in fiber which increases microbiota resiliency by inducing production of the quorum sensing molecule AI-2 which stabilizes Firmicutes in the face of antibiotic exposure. The western diet alterations not only destabilize metabolite production of the gut microbiota, but also increase the presence of antibiotic resistance genes independent of antibiotic exposure conferring resistance to macrolides, fluoroquinolones, and cephalosporins. Gut-derived metabolites such as indoles were found to drive a recovery directed immune response in mice exposed to lethal bacterial peritonitis. During lethal infection, indole metabolites enhanced survival by activating AhR on macrophages which increased bacterial clearance and induce resolution of inflammation. Oral supplementation with tryptophan or direct injection of indole metabolites improved survival in this model. To further implicate the importance of indole activation of AhR, select bacterial pathogens actively inhibited indole activation of AhR via the secretion of small molecules such as enterobactin. Finally, indole metabolites in the gut of septic patients correlated with survival. In conclusion, the structure and function of the gut microbiota is influenced by diet and has major downstream implications on pathogen colonization, virulence expression and survival from a lethal bacterial infection such as murine peritonitis.

English

ISBN: 9798382782638Subjects--Topical Terms:

234377
Surgery.
Subjects--Index Terms:

Aryl hydrocarbon receptor

Host-Pathogen-Gut Microbiota Interactions: The Role of Diet, Microbiota Metabolites, and the Aryl Hydrocarbon Receptor in Survival From Sepsis and Surgical Injury /
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