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Bacterial nutrient foraging in a mouse model of enteral nutrient deprivation: insight into the gut origin of sepsis.

Authors :
Ralls MW
Demehri FR
Feng Y
Raskind S
Ruan C
Schintlmeister A
Loy A
Hanson B
Berry D
Burant CF
Teitelbaum DH
Source :
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2016 Oct 01; Vol. 311 (4), pp. G734-G743. Date of Electronic Publication: 2016 Sep 01.
Publication Year :
2016

Abstract

Total parenteral nutrition (TPN) leads to a shift in small intestinal microbiota with a characteristic dominance of Proteobacteria This study examined how metabolomic changes within the small bowel support an altered microbial community in enterally deprived mice. C57BL/6 mice were given TPN or enteral chow. Metabolomic analysis of jejunal contents was performed by liquid chromatography/mass spectrometry (LC/MS). In some experiments, leucine in TPN was partly substituted with [ <superscript>13</superscript> C]leucine. Additionally, jejunal contents from TPN-dependent and enterally fed mice were gavaged into germ-free mice to reveal whether the TPN phenotype was transferrable. Small bowel contents of TPN mice maintained an amino acid composition similar to that of the TPN solution. Mass spectrometry analysis of small bowel contents of TPN-dependent mice showed increased concentration of <superscript>13</superscript> C compared with fed mice receiving saline enriched with [ <superscript>13</superscript> C]leucine. [ <superscript>13</superscript> C]leucine added to the serosal side of Ussing chambers showed rapid permeation across TPN-dependent jejunum, suggesting increased transmucosal passage. Single-cell analysis by fluorescence in situ hybridization (FISH)-NanoSIMS demonstrated uptake of [ <superscript>13</superscript> C]leucine by TPN-associated bacteria, with preferential uptake by Enterobacteriaceae Gavage of small bowel effluent from TPN mice into germ-free, fed mice resulted in a trend toward the proinflammatory TPN phenotype with loss of epithelial barrier function. TPN dependence leads to increased permeation of TPN-derived nutrients into the small intestinal lumen, where they are predominately utilized by Enterobacteriaceae The altered metabolomic composition of the intestinal lumen during TPN promotes dysbiosis.<br /> (Copyright © 2016 the American Physiological Society.)

Details

Language :
English
ISSN :
1522-1547
Volume :
311
Issue :
4
Database :
MEDLINE
Journal :
American journal of physiology. Gastrointestinal and liver physiology
Publication Type :
Academic Journal
Accession number :
27586649
Full Text :
https://doi.org/10.1152/ajpgi.00088.2016