Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

ABSTRACT Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors...

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Autores principales:	Sanjiv K. Hyoju, Alexander Zaborin, Robert Keskey, Anukriti Sharma, Wyatt Arnold, Fons van den Berg, Sangman M. Kim, Neil Gottel, Cindy Bethel, Angella Charnot-Katsikas, Peng Jianxin, Carleen Adriaansens, Emily Papazian, Jack A. Gilbert, Olga Zaborina, John C. Alverdy
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Western diet gut microbiome gut-derived sepsis pathobionts surgery Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/987ac7b19e284871ac3edc524ace133f
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spelling	oai:doaj.org-article:987ac7b19e284871ac3edc524ace133f2021-11-15T16:22:10ZMice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts10.1128/mBio.00903-192150-7511https://doaj.org/article/987ac7b19e284871ac3edc524ace133f2019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00903-19https://doaj.org/toc/2150-7511ABSTRACT Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.Sanjiv K. HyojuAlexander ZaborinRobert KeskeyAnukriti SharmaWyatt ArnoldFons van den BergSangman M. KimNeil GottelCindy BethelAngella Charnot-KatsikasPeng JianxinCarleen AdriaansensEmily PapazianJack A. GilbertOlga ZaborinaJohn C. AlverdyAmerican Society for MicrobiologyarticleWestern dietgut microbiomegut-derived sepsispathobiontssurgeryMicrobiologyQR1-502ENmBio, Vol 10, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Western diet gut microbiome gut-derived sepsis pathobionts surgery Microbiology QR1-502
spellingShingle	Western diet gut microbiome gut-derived sepsis pathobionts surgery Microbiology QR1-502 Sanjiv K. Hyoju Alexander Zaborin Robert Keskey Anukriti Sharma Wyatt Arnold Fons van den Berg Sangman M. Kim Neil Gottel Cindy Bethel Angella Charnot-Katsikas Peng Jianxin Carleen Adriaansens Emily Papazian Jack A. Gilbert Olga Zaborina John C. Alverdy Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
description	ABSTRACT Despite antibiotics and sterile technique, postoperative infections remain a real and present danger to patients. Recent estimates suggest that 50% of the pathogens associated with postoperative infections have become resistant to the standard antibiotics used for prophylaxis. Risk factors identified in such cases include obesity and antibiotic exposure. To study the combined effect of obesity and antibiotic exposure on postoperative infection, mice were allowed to gain weight on an obesogenic Western-type diet (WD), administered antibiotics and then subjected to an otherwise recoverable sterile surgical injury (30% hepatectomy). The feeding of a WD alone resulted in a major imbalance of the cecal microbiota characterized by a decrease in diversity, loss of Bacteroidetes, a bloom in Proteobacteria, and the emergence of antibiotic-resistant organisms among the cecal microbiota. When WD-fed mice were administered antibiotics and subjected to 30% liver resection, lethal sepsis, characterized by multiple-organ damage, developed. Notable was the emergence and systemic dissemination of multidrug-resistant (MDR) pathobionts, including carbapenem-resistant, extended-spectrum β-lactamase-producing Serratia marcescens, which expressed a virulent and immunosuppressive phenotype. Analysis of the distribution of exact sequence variants belonging to the genus Serratia suggested that these strains originated from the cecal mucosa. No mortality or MDR pathogens were observed in identically treated mice fed a standard chow diet. Taken together, these results suggest that consumption of a Western diet and exposure to certain antibiotics may predispose to life-threating postoperative infection associated with MDR organisms present among the gut microbiota. IMPORTANCE Obesity remains a prevalent and independent risk factor for life-threatening infection following major surgery. Here, we demonstrate that when mice are fed an obesogenic Western diet (WD), they become susceptible to lethal sepsis with multiple organ damage after exposure to antibiotics and an otherwise-recoverable surgical injury. Analysis of the gut microbiota in this model demonstrates that WD alone leads to loss of Bacteroidetes, a bloom of Proteobacteria, and evidence of antibiotic resistance development even before antibiotics are administered. After antibiotics and surgery, lethal sepsis with organ damage developed in in mice fed a WD with the appearance of multidrug-resistant pathogens in the liver, spleen, and blood. The importance of these findings lies in exposing how the selective pressures of diet, antibiotic exposure, and surgical injury can converge on the microbiome, resulting in lethal sepsis and organ damage without the introduction of an exogenous pathogen.
format	article
author	Sanjiv K. Hyoju Alexander Zaborin Robert Keskey Anukriti Sharma Wyatt Arnold Fons van den Berg Sangman M. Kim Neil Gottel Cindy Bethel Angella Charnot-Katsikas Peng Jianxin Carleen Adriaansens Emily Papazian Jack A. Gilbert Olga Zaborina John C. Alverdy
author_facet	Sanjiv K. Hyoju Alexander Zaborin Robert Keskey Anukriti Sharma Wyatt Arnold Fons van den Berg Sangman M. Kim Neil Gottel Cindy Bethel Angella Charnot-Katsikas Peng Jianxin Carleen Adriaansens Emily Papazian Jack A. Gilbert Olga Zaborina John C. Alverdy
author_sort	Sanjiv K. Hyoju
title	Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
title_short	Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
title_full	Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
title_fullStr	Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
title_full_unstemmed	Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts
title_sort	mice fed an obesogenic western diet, administered antibiotics, and subjected to a sterile surgical procedure develop lethal septicemia with multidrug-resistant pathobionts
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/987ac7b19e284871ac3edc524ace133f
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Mice Fed an Obesogenic Western Diet, Administered Antibiotics, and Subjected to a Sterile Surgical Procedure Develop Lethal Septicemia with Multidrug-Resistant Pathobionts

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