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Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial
Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial

BACKGROUND: Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH).

OBJECTIVE: We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE.

METHODS: AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes.

RESULTS: Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH.

CONCLUSIONS: In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.

Adult, Amino Acids/administration & dosage, Bacterial Translocation, Dietary Supplements, Female, Glutamine/administration & dosage, Humans, Intestinal Diseases/prevention & control, Intestinal Mucosa/pathology, Intestine, Small/metabolism, Leucine/administration & dosage, Male, Mechanistic Target of Rapamycin Complex 1/metabolism, Micronutrients/administration & dosage, Middle Aged, Tryptophan/administration & dosage
0002-9165
1240-1252
Louis-Auguste, John
911ff61c-960f-4432-a28f-d72eab12bd11
Besa, Ellen
e8c57533-2585-4133-bc6f-3f7978ba84cd
Zyambo, Kanekwa
911d093a-cd47-4fe0-807e-29fde79cc73f
Munkombwe, Derick
a160631b-3160-4108-987d-027bd3b6bab5
Banda, Rosemary
b06163c2-524c-46d7-93f3-664eb7242773
Banda, Themba
2f63dce2-f740-4d26-89a2-d20ea3108839
Watson, Alastair
67936648-9486-403c-96b4-95aea4e833b4
Mayneris-Perxachs, Jordi
921cd6b1-1c40-4cb6-9d70-9d3c4f479a78
Swann, Jonathan
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Kelly, Paul
1ea49b1b-f831-425f-816d-ce2dfa663686
Louis-Auguste, John
911ff61c-960f-4432-a28f-d72eab12bd11
Besa, Ellen
e8c57533-2585-4133-bc6f-3f7978ba84cd
Zyambo, Kanekwa
911d093a-cd47-4fe0-807e-29fde79cc73f
Munkombwe, Derick
a160631b-3160-4108-987d-027bd3b6bab5
Banda, Rosemary
b06163c2-524c-46d7-93f3-664eb7242773
Banda, Themba
2f63dce2-f740-4d26-89a2-d20ea3108839
Watson, Alastair
67936648-9486-403c-96b4-95aea4e833b4
Mayneris-Perxachs, Jordi
921cd6b1-1c40-4cb6-9d70-9d3c4f479a78
Swann, Jonathan
7c11a66b-f4b8-4dbf-aa17-ad8b0561b85c
Kelly, Paul
1ea49b1b-f831-425f-816d-ce2dfa663686

Louis-Auguste, John, Besa, Ellen, Zyambo, Kanekwa, Munkombwe, Derick, Banda, Rosemary, Banda, Themba, Watson, Alastair, Mayneris-Perxachs, Jordi, Swann, Jonathan and Kelly, Paul (2019) Tryptophan, glutamine, leucine, and micronutrient supplementation improves environmental enteropathy in Zambian adults: a randomized controlled trial. The American Journal of Clinical Nutrition, 110 (5), 1240-1252. (doi:10.1093/ajcn/nqz189).

Record type: Article

Abstract

BACKGROUND: Environmental enteropathy (EE) refers to villus blunting, reduced absorption, and microbial translocation in children and adults in tropical or deprived residential areas. In previous work we observed an effect of micronutrients on villus height (VH).

OBJECTIVE: We aimed to determine, in a randomized controlled trial, if amino acid (AA) or multiple micronutrient (MM) supplementation can improve intestinal structure or barrier dysfunction in Zambian adults with EE.

METHODS: AA (tryptophan, leucine, and glutamine) and/or MM supplements were given for 16 wk in a 2 × 2 factorial comparison against placebo. Primary outcomes were changes in VH, in vivo small intestinal barrier dysfunction assessed by confocal laser endomicroscopy (CLE), and mechanistic (or mammalian) target of rapamycin complex 1 (MTORC1) nutrient responsiveness in lamina propria CD4+ lymphocytes.

RESULTS: Over 16 wk AA, but not MM, supplementation increased VH by 16% (34.5 μm) compared with placebo (P = 0.04). Fluorescein leak, measured by CLE, improved only in those allocated to both AA and MM supplementation. No effect was seen on MTORC1 activation, but posttreatment MTORC1 and VH were correlated (ρ = 0.51; P = 0.001), and change in MTORC1 was correlated with change in VH in the placebo group (ρ = 0.63; P = 0.03). In secondary analyses no effect was observed on biomarkers of microbial translocation. Metabolomic analyses suggest alterations in a number of microbial- and host-derived metabolites including the leucine metabolite β-hydroxy-β-methylbutyrate, which was increased by AA supplementation and correlated with VH.

CONCLUSIONS: In this phase 2 trial, AA supplementation protected against a decline in VH over the supplementation period, and improved barrier function when combined with micronutrients. Leucine and MTORC1 metabolism may be involved in the mechanism of effect. This trial was registered at www.pactr.org as PACTR201505001104412.

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Accepted/In Press date: 18 July 2019
e-pub ahead of print date: 28 August 2019
Published date: 1 November 2019
Keywords: Adult, Amino Acids/administration & dosage, Bacterial Translocation, Dietary Supplements, Female, Glutamine/administration & dosage, Humans, Intestinal Diseases/prevention & control, Intestinal Mucosa/pathology, Intestine, Small/metabolism, Leucine/administration & dosage, Male, Mechanistic Target of Rapamycin Complex 1/metabolism, Micronutrients/administration & dosage, Middle Aged, Tryptophan/administration & dosage

Identifiers

Local EPrints ID: 440777
URI: http://eprints.soton.ac.uk/id/eprint/440777
ISSN: 0002-9165
PURE UUID: 086f8162-7757-4c57-895b-31cdc3ca0650
ORCID for Jonathan Swann: ORCID iD orcid.org/0000-0002-6485-4529

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Date deposited: 18 May 2020 16:33
Last modified: 23 May 2020 00:47

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Contributors

Author: John Louis-Auguste
Author: Ellen Besa
Author: Kanekwa Zyambo
Author: Derick Munkombwe
Author: Rosemary Banda
Author: Themba Banda
Author: Alastair Watson
Author: Jordi Mayneris-Perxachs
Author: Jonathan Swann ORCID iD
Author: Paul Kelly

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