Piglet cardiopulmonary bypass induces intestinal dysbiosis and barrier dysfunction associated with systemic inflammation

Author:

Salomon Jeffrey D.12ORCID,Qiu Haowen3,Feng Dan4,Owens Jacob1,Khailova Ludmila5,Osorio Lujan Suzanne5,Iguidbashian John5,Chhonker Yashpal S.6,Murry Daryl J.6,Riethoven Jean-Jack3,Lindsey Merry L.78,Singh Amar B.89,Davidson Jesse A.5

Affiliation:

1. University of Nebraska Medical Center 1 Department of Pediatrics , , Omaha, NE 68102 , USA

2. University of Nebraska Medical Center 2 Department of Cellular & Integrative Physiology , , Omaha, NE 68102 , USA

3. Center for Biotechnology, University of Nebraska Lincoln 3 , Lincoln, NE 68588 , USA

4. University of Nebraska Medical Center 4 Department of Hematology/Oncology , , Omaha, NE 68102 , USA

5. University of Colorado 5 Department of Pediatrics , , Aurora, CO 80045 , USA

6. University of Nebraska Medical Center College of Pharmacy 6 Department of Pharmacy Practice , , Omaha, NE 68102 , USA

7. School of Graduate Studies and Research, Meharry Medical College 7 , Nashville, TN 37208 , USA

8. Research Service, Nebraska-Western Iowa Health Care System 8 , Omaha, NE 68105 , USA

9. University of Nebraska Medical Center 9 Department of Biochemistry & Molecular Biology , , Omaha, NE 68102 , USA

Abstract

ABSTRACT The intestinal microbiome is essential to human health and homeostasis, and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery post-operatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB is necessary. We used a piglet model of CPB with two groups, CPB (n=5) and a control group with mechanical ventilation (n=7), to evaluate changes to the microbiome, intestinal barrier dysfunction and intestinal metabolites with inflammation after CPB. We identified significant changes to the microbiome, barrier dysfunction, intestinal short-chain fatty acids and eicosanoids, and elevated cytokines in the CPB/deep hypothermic circulatory arrest group compared to the control group at just 4 h after intervention. This piglet model of CPB replicates known human changes to intestinal flora and metabolite profiles, and can be used to evaluate gut interventions aimed at reducing downstream inflammation after cardiac surgery with CPB.

Funder

National Institutes of Health

U.S. Department of Defense

American Heart Association

Biomedical Laboratory Research and Development, VA Office of Research and Development

University of Nebraska Medical Center

Publisher

The Company of Biologists

Subject

General Biochemistry, Genetics and Molecular Biology,Immunology and Microbiology (miscellaneous),Medicine (miscellaneous),Neuroscience (miscellaneous)

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