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Glutamine and intestinal barrier function

Amino Acids volume 47, pages 2143–2154 (2015)Cite this article

Abstract

The intestinal barrier integrity is essential for the absorption of nutrients and health in humans and animals. Dysfunction of the mucosal barrier is associated with increased gut permeability and development of multiple gastrointestinal diseases. Recent studies highlighted a critical role for glutamine, which had been traditionally considered as a nutritionally non-essential amino acid, in activating the mammalian target of rapamycin cell signaling in enterocytes. In addition, glutamine has been reported to enhance intestinal and whole-body growth, to promote enterocyte proliferation and survival, and to regulate intestinal barrier function in injury, infection, weaning stress, and other catabolic conditions. Mechanistically, these effects were mediated by maintaining the intracellular redox status and regulating expression of genes associated with various signaling pathways. Furthermore, glutamine stimulates growth of the small intestinal mucosa in young animals and also enhances ion transport by the gut in neonates and adults. Growing evidence supports the notion that glutamine is a nutritionally essential amino acid for neonates and a conditionally essential amino acid for adults. Thus, as a functional amino acid with multiple key physiological roles, glutamine holds great promise in protecting the gut from atrophy and injury under various stress conditions in mammals and other animals.

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Abbreviations

ASCT2:

Neutral amino acid transporter type 2

ATP:

Adenosine triphosphate

BSO:

Buthionine sulfoximine

DP:

Dipeptidase

EAA:

Essential amino acids

4EBP1:

Eukaryotic translation initiation factor 4E-binding protein-1

eIF4E:

Eukaryotic translation initiation factor 4E

FOXO:

Forkhead box O transcription factor

GA:

GlutaminaseGALT gut-associated lymphatic tissue

GCL:

Glutamate cysteine ligase

GS:

Glutamine synthetase

GSH:

Glutathione

GSS:

Glutathione synthetase

GSSG:

Glutathione disulfide

γ-GT:

γ-Glutamyl transpeptidase

Ig:

Immunoglobulin

IκB:

Inhibitor of NF-κB

α-KG:

α-Ketoglutarate

IUGR:

Intrauterine growth restriction

MAPK:

Mitogen-activated protein kinases

MS:

Methionine sulfoximine

mTOR:

Mammalian target of rapamycin

mTORC:

mTOR complex

NADH:

Reduced form of nicotinamide adenine dinucleotide

NADPH:

Reduced form of nicotinamide adenine dinucleotide phosphate

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

NOS:

NO synthase

p70S6k:

p70 Ribosomal protein S6 kinase

PI3K:

Phosphatidylinositol 3-kinase

PKB/AKT:

Protein kinase B

PPP:

Pentose phosphate pathway

Rheb:

Ras homologue enriched in brain

ROS:

Reactive oxygen species

RTK:

Receptor tyrosine kinase

SNAT2:

Sodium coupled neutral amino acid transporter 2

TCL:

Tricarboxylic acid cycle

TNF-α:

Tumor necrosis factor-alpha

TPN:

Total parenteral nutrition

Trx:

Reduced thioredoxin

TrxSS:

Oxidized thioredoxin

TSC:

Tuberous sclerosis complex

ZO-1:

Zonula occludens protein 1

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Acknowledgments

This work was supported by National Key Basic Research Program (2013CB127302), the Natural Science Foundation of China (31172217, 31272450, 31301979, and 31272451), the Chinese Universities Scientific Fund (2013RC002), the Program for New Century Excellent Talents in University (NCET-12-0522), and the Program for Beijing Municipal Excellent Talents, and Texas A&M AgriLife Research (H-8200).

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, People’s Republic of China

    Bin Wang, Guoyao Wu, Zhaolai Dai, Yuli Sun, Yun Ji, Wei Li, Weiwei Wang, Chuang Liu, Feng Han & Zhenlong Wu

  2. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

  3. Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China

    Zhigang Zhou

Authors
  1. Bin Wang
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  2. Guoyao Wu
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  3. Zhigang Zhou
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  4. Zhaolai Dai
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  5. Yuli Sun
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  6. Yun Ji
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  7. Wei Li
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  8. Weiwei Wang
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  9. Chuang Liu
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  10. Feng Han
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  11. Zhenlong Wu
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Correspondence to Zhenlong Wu.

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Wang, B., Wu, G., Zhou, Z. et al. Glutamine and intestinal barrier function. Amino Acids 47, 2143–2154 (2015). https://doi.org/10.1007/s00726-014-1773-4

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  • DOI: https://doi.org/10.1007/s00726-014-1773-4

Keywords

  • Glutamine
  • Intestinal barrier function
  • Nutrition