PMID- 27586649 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20230728 IS - 1522-1547 (Electronic) IS - 0193-1857 (Print) IS - 0193-1857 (Linking) VI - 311 IP - 4 DP - 2016 Oct 1 TI - Bacterial nutrient foraging in a mouse model of enteral nutrient deprivation: insight into the gut origin of sepsis. PG - G734-G743 LID - 10.1152/ajpgi.00088.2016 [doi] AB - 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 [(13)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 (13)C compared with fed mice receiving saline enriched with [(13)C]leucine. [(13)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 [(13)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. CI - Copyright (c) 2016 the American Physiological Society. FAU - Ralls, Matthew W AU - Ralls MW AD - Department of Surgery, Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan; mralls@med.umich.edu. FAU - Demehri, Farokh R AU - Demehri FR AD - Department of Surgery, Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan. FAU - Feng, Yongjia AU - Feng Y AD - Department of Surgery, Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan. FAU - Raskind, Sasha AU - Raskind S AD - Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, Michigan. FAU - Ruan, Chunhai AU - Ruan C AD - Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, Michigan. FAU - Schintlmeister, Arno AU - Schintlmeister A AD - Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry Meets Microbiology, University of Vienna, Vienna, Austria. AD - Large-Instrument Facility for Advanced Isotope Research, University of Vienna, Vienna, Austria; and. FAU - Loy, Alexander AU - Loy A AD - Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry Meets Microbiology, University of Vienna, Vienna, Austria. FAU - Hanson, Buck AU - Hanson B AD - Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry Meets Microbiology, University of Vienna, Vienna, Austria. FAU - Berry, David AU - Berry D AD - Division of Microbial Ecology, Department of Microbiology and Ecosystem Science, Research Network Chemistry Meets Microbiology, University of Vienna, Vienna, Austria. FAU - Burant, Charles F AU - Burant CF AD - Michigan Regional Comprehensive Metabolomics Resource Core, University of Michigan, Ann Arbor, Michigan. AD - Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan. FAU - Teitelbaum, Daniel H AU - Teitelbaum DH AD - Department of Surgery, Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan. LA - eng GR - P30 DK089503/DK/NIDDK NIH HHS/United States GR - R01 AI044076/AI/NIAID NIH HHS/United States GR - U24 DK097153/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160901 PL - United States TA - Am J Physiol Gastrointest Liver Physiol JT - American journal of physiology. Gastrointestinal and liver physiology JID - 100901227 SB - IM MH - Animals MH - Disease Models, Animal MH - Gastrointestinal Microbiome/*physiology MH - Intestinal Mucosa/*metabolism/microbiology MH - Jejunum/*metabolism/microbiology MH - Male MH - Metabolome MH - Mice MH - Mice, Inbred C57BL MH - *Parenteral Nutrition, Total MH - Sepsis/*metabolism/microbiology PMC - PMC5142194 OTO - NOTNLM OT - NanoSIMS OT - epithelial barrier function OT - metabolome OT - microbiota OT - nutrient foraging OT - total parenteral nutrition EDAT- 2016/09/03 06:00 MHDA- 2017/06/27 06:00 PMCR- 2017/10/01 CRDT- 2016/09/03 06:00 PHST- 2016/02/29 00:00 [received] PHST- 2016/08/22 00:00 [accepted] PHST- 2016/09/03 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] PHST- 2016/09/03 06:00 [entrez] PHST- 2017/10/01 00:00 [pmc-release] AID - ajpgi.00088.2016 [pii] AID - GI-00088-2016 [pii] AID - 10.1152/ajpgi.00088.2016 [doi] PST - ppublish SO - Am J Physiol Gastrointest Liver Physiol. 2016 Oct 1;311(4):G734-G743. doi: 10.1152/ajpgi.00088.2016. Epub 2016 Sep 1.