Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice

Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We i...

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Main Authors: Arista Nienaber, Jeannine Baumgartner, Robin C. Dolman, Mumin Ozturk, Lizelle Zandberg, Frank E. A. Hayford, Frank Brombacher, Renee Blaauw, Suraj P. Parihar, Cornelius M. Smuts, Linda Malan
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/12/9/2897
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author Arista Nienaber
Jeannine Baumgartner
Robin C. Dolman
Mumin Ozturk
Lizelle Zandberg
Frank E. A. Hayford
Frank Brombacher
Renee Blaauw
Suraj P. Parihar
Cornelius M. Smuts
Linda Malan
author_facet Arista Nienaber
Jeannine Baumgartner
Robin C. Dolman
Mumin Ozturk
Lizelle Zandberg
Frank E. A. Hayford
Frank Brombacher
Renee Blaauw
Suraj P. Parihar
Cornelius M. Smuts
Linda Malan
author_sort Arista Nienaber
collection DOAJ
description Progressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in <i>Mycobacterium tuberculosis</i>-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.
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spelling doaj.art-dc01abf9aa0e4ce996e14d067fb651e62023-11-20T14:41:08ZengMDPI AGNutrients2072-66432020-09-01129289710.3390/nu12092897Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected MiceArista Nienaber0Jeannine Baumgartner1Robin C. Dolman2Mumin Ozturk3Lizelle Zandberg4Frank E. A. Hayford5Frank Brombacher6Renee Blaauw7Suraj P. Parihar8Cornelius M. Smuts9Linda Malan10Centre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town-Component, University of Cape Town, Cape Town 7925, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town-Component, University of Cape Town, Cape Town 7925, South AfricaDivision of Human Nutrition, Stellenbosch University, Tygerberg, Cape Town 7505, South AfricaInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town-Component, University of Cape Town, Cape Town 7925, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaCentre of Excellence for Nutrition, North-West University, Potchefstroom 2531, South AfricaProgressive inflammation and anemia are common in tuberculosis (TB) and linked to poor clinical outcomes. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have inflammation-resolving properties, whereas iron supplementation in TB may have limited efficacy and enhance bacterial growth. We investigated effects of iron and EPA/DHA supplementation, alone and in combination, on inflammation, anemia, iron status markers and clinical outcomes in <i>Mycobacterium tuberculosis</i>-infected C3HeB/FeJ mice. One week post-infection, mice received the AIN-93 diet without (control) or with supplemental iron (Fe), EPA/DHA, or Fe+EPA/DHA for 3 weeks. Mice supplemented with Fe or EPA/DHA had lower soluble transferrin receptor, ferritin and hepcidin than controls, but these effects were attenuated in Fe+EPA/DHA mice. EPA/DHA increased inflammation-resolving lipid mediators and lowered lung IL-1α, IFN-γ, plasma IL-1β, and TNF-α. Fe lowered lung IL-1α, IL-1β, plasma IL-1β, TNF-α, and IL-6. However, the cytokine-lowering effects in the lungs were attenuated with Fe+EPA/DHA. Mice supplemented with EPA/DHA had lower lung bacterial loads than controls, but this effect was attenuated in Fe+EPA/DHA mice. Thus, individually, post-infection EPA/DHA and iron supplementation lowered systemic and lung inflammation and mitigated anemia of infection in TB, but not when combined. EPA/DHA also enhanced bactericidal effects and could support inflammation resolution and management of anemia.https://www.mdpi.com/2072-6643/12/9/2897anemia of infectiondocosahexaenoic acideicosapentaenoic acidinflammationirontuberculosis
spellingShingle Arista Nienaber
Jeannine Baumgartner
Robin C. Dolman
Mumin Ozturk
Lizelle Zandberg
Frank E. A. Hayford
Frank Brombacher
Renee Blaauw
Suraj P. Parihar
Cornelius M. Smuts
Linda Malan
Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
Nutrients
anemia of infection
docosahexaenoic acid
eicosapentaenoic acid
inflammation
iron
tuberculosis
title Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
title_full Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
title_fullStr Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
title_full_unstemmed Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
title_short Omega-3 Fatty Acid and Iron Supplementation Alone, but Not in Combination, Lower Inflammation and Anemia of Infection in <i>Mycobacterium tuberculosis</i>-Infected Mice
title_sort omega 3 fatty acid and iron supplementation alone but not in combination lower inflammation and anemia of infection in i mycobacterium tuberculosis i infected mice
topic anemia of infection
docosahexaenoic acid
eicosapentaenoic acid
inflammation
iron
tuberculosis
url https://www.mdpi.com/2072-6643/12/9/2897
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