Beneficial effect of long-chain n-3 polyunsaturated fatty acid supplementation on tuberculosis in mice

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 170; p. 102304
• Main Authors: Nienaber, Arista, Ozturk, Mumin, Dolman, Robin C, Zandberg, Lizelle, Hayford, Frank EA, Brombacher, Frank, Blaauw, Renee, Smuts, Cornelius M, Parihar, Suraj P, Malan, Linda
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-07-2021
• Subjects: Animals; Body Weight - drug effects; Dietary Supplements; Disease Models, Animal; Docosahexaenoic acid; Docosahexaenoic Acids - pharmacology; Eicosapentaenoic acid; Eicosapentaenoic Acid - pharmacology; Fatty Acids - blood; Fatty Acids, Omega-3 - pharmacology; Inflammation; Low n-3 fatty acid status; Lung - drug effects; Lung - immunology; Lung - pathology; Mice; N-3 essential fatty acids; Tuberculosis; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - pathology; N-3 essential fatty acids; Inflammation; Tuberculosis; Low n-3 fatty acid status; Docosahexaenoic acid; Eicosapentaenoic acid
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2021.102304

•EPA/DHA enhance bactericidal effects in TB.•EPA/DHA promotes lung inflammation resolution and improved weight gain in TB.•Immune cell and lung EPA/DHA composition inversely correlate with pro-inflammatory lung cytokine levels.
Intakes of the omega-3 essential fatty acids (n-3 EFAs) are low in the general adult population, with high n-6/n-3 polyunsaturated fatty acid (PUFA) ratios and the accompanying suboptimal n-3 PUFA status. Eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) have antibacterial and inflammation-resolving effects in tuberculosis (TB). However, whether switching to a diet with optimum n-3 EFA intake after the infection has comparable benefits has not been investigated. We aimed to compare the effects of a diet with sufficient n-3 EFA content in an acceptable n-6/n-3 PUFA ratio for rodents ((n-3)eFAS group) with those on the same diet supplemented with EPA and DHA (EPA/DHA group) in Mycobacterium tuberculosis (Mtb)-infected C3HeB/FeJ mice with a low n-3 PUFA status. Mice were conditioned on an n-3 PUFA-deficient diet with a high n-6/n-3 PUFA ratio for 6 weeks before Mtb infection and randomized to either (n-3)eFAS or EPA/DHA diets 1 week post-infection for 3 weeks. At endpoint, EPA and DHA compositions were higher and arachidonic acid, osbond acid, and total n-6 LCPUFAs lower in all lipid pools measured in the EPA/DHA group (all P < 0.001). Percentage body weight gain was higher (P = 0.017) and lung bacterial load lower (P < 0.001) in the EPA/DHA group. Additionally, the EPA/DHA group had a more pro-resolving lung lipid mediator profile and lower lung in IL-1α and IL-1β concentrations (P = 0.023, P = 0.049). Inverse correlations were found between the lung and peripheral blood mononuclear cell EPA and DHA and selected pro-inflammatory cytokines. These are the first findings that indicate that EPA/DHA supplementation provides benefits superior to a diet with sufficient n-3 EFAs concerning bacterial killing, weight gain and lung inflammation resolution in Mtb-infected mice with a low n-3 PUFA status. Therefore, EPA and DHA may be worth considering as adjunct TB treatment.