Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids
Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diab...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/6014631 |
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| _version_ | 1832565181450813440 |
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| author | Ekta Lachmandas Corina N. A. M. van den Heuvel Michelle S. M. A. Damen Maartje C. P. Cleophas Mihai G. Netea Reinout van Crevel |
| author_facet | Ekta Lachmandas Corina N. A. M. van den Heuvel Michelle S. M. A. Damen Maartje C. P. Cleophas Mihai G. Netea Reinout van Crevel |
| author_sort | Ekta Lachmandas |
| collection | DOAJ |
| description | Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate’s well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis. |
| format | Article |
| id | doaj-art-975ad265140f493393de877701c0b023 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-975ad265140f493393de877701c0b0232025-02-03T01:09:07ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/60146316014631Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty AcidsEkta Lachmandas0Corina N. A. M. van den Heuvel1Michelle S. M. A. Damen2Maartje C. P. Cleophas3Mihai G. Netea4Reinout van Crevel5Department of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsDepartment of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsDepartment of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsDepartment of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsDepartment of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsDepartment of Internal Medicine and Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Internal Postal Code 463, P.O. Box 9101, 6500 HB Nijmegen, NetherlandsType 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate’s well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis.http://dx.doi.org/10.1155/2016/6014631 |
| spellingShingle | Ekta Lachmandas Corina N. A. M. van den Heuvel Michelle S. M. A. Damen Maartje C. P. Cleophas Mihai G. Netea Reinout van Crevel Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids Journal of Diabetes Research |
| title | Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids |
| title_full | Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids |
| title_fullStr | Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids |
| title_full_unstemmed | Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids |
| title_short | Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids |
| title_sort | diabetes mellitus and increased tuberculosis susceptibility the role of short chain fatty acids |
| url | http://dx.doi.org/10.1155/2016/6014631 |
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