Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis
Mitochondrial dysfunction and immune cell dysfunction are commonplace in sepsis and are associated with increased mortality risk. The short chain fatty acid, butyrate, is known to have anti-inflammatory effects and promote mitochondrial biogenesis. We therefore explored the immunometabolic effects o...
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MDPI AG
2022-12-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/12/2034 |
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| author | Vera B. M. Peters Nishkantha Arulkumaran Miranda J. Melis Charlotte Gaupp Thierry Roger Manu Shankar-Hari Mervyn Singer |
| author_facet | Vera B. M. Peters Nishkantha Arulkumaran Miranda J. Melis Charlotte Gaupp Thierry Roger Manu Shankar-Hari Mervyn Singer |
| author_sort | Vera B. M. Peters |
| collection | DOAJ |
| description | Mitochondrial dysfunction and immune cell dysfunction are commonplace in sepsis and are associated with increased mortality risk. The short chain fatty acid, butyrate, is known to have anti-inflammatory effects and promote mitochondrial biogenesis. We therefore explored the immunometabolic effects of butyrate in an animal model of sepsis. Isolated healthy human volunteer peripheral mononuclear cells were stimulated with LPS in the presence of absence of butyrate, and released cytokines measured. Male Wistar rats housed in metabolic cages received either intravenous butyrate infusion or placebo commencing 6 h following faecal peritonitis induction. At 24 h, splenocytes were isolated for high-resolution respirometry, and measurement of mitochondrial membrane potential (MMP), reactive oxygen species (mtROS), and intracellular cytokines (TNF alpha, IL-10) using flow cytometry. Isolated splenocytes from septic and septic butyrate treated rats were stimulated with LPS for 18 h and the effects of butyrate on cytokine release assessed. Ex vivo, butyrate (1.8 mM) reduced LPS-induced TNF alpha (<i>p</i> = 0.019) and IL-10 (<i>p</i> = 0.001) release by human PBMCs. In septic animals butyrate infusion reduced the respiratory exchange ratio (<i>p</i> < 0.001), consistent with increased fat metabolism. This was associated with a reduction in cardiac output (<i>p</i> = 0.001), and increased lactate (<i>p</i> = 0.031) compared to placebo-treated septic animals (<i>p</i> < 0.05). Butyrate treatment was associated with a reduction in splenocyte basal respiration (<i>p</i> = 0.077), proton leak (<i>p</i> = 0.022), and non-mitochondrial respiration (<i>p</i> = 0.055), and an increase in MMP (<i>p</i> = 0.007) and mtROS (<i>p</i> = 0.027) compared to untreated septic animals. Splenocyte intracellular cytokines were unaffected by butyrate, although LPS-induced IL-10 release was impaired (<i>p</i> = 0.039). In summary, butyrate supplementation exacerbates myocardial and immune cell mitochondrial dysfunction in a rat model of faecal peritonitis. |
| first_indexed | 2024-03-09T16:11:15Z |
| format | Article |
| id | doaj.art-aa72f13338ef45159e0ae8e75a4ed06c |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T16:11:15Z |
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| spelling | doaj.art-aa72f13338ef45159e0ae8e75a4ed06c2023-11-24T16:12:25ZengMDPI AGLife2075-17292022-12-011212203410.3390/life12122034Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal PeritonitisVera B. M. Peters0Nishkantha Arulkumaran1Miranda J. Melis2Charlotte Gaupp3Thierry Roger4Manu Shankar-Hari5Mervyn Singer6Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London WC1E 6BT, UKBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London WC1E 6BT, UKBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London WC1E 6BT, UKBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London WC1E 6BT, UKInfectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, CH-1066 Lausanne, SwitzerlandCentre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4TJ, UKBloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, London WC1E 6BT, UKMitochondrial dysfunction and immune cell dysfunction are commonplace in sepsis and are associated with increased mortality risk. The short chain fatty acid, butyrate, is known to have anti-inflammatory effects and promote mitochondrial biogenesis. We therefore explored the immunometabolic effects of butyrate in an animal model of sepsis. Isolated healthy human volunteer peripheral mononuclear cells were stimulated with LPS in the presence of absence of butyrate, and released cytokines measured. Male Wistar rats housed in metabolic cages received either intravenous butyrate infusion or placebo commencing 6 h following faecal peritonitis induction. At 24 h, splenocytes were isolated for high-resolution respirometry, and measurement of mitochondrial membrane potential (MMP), reactive oxygen species (mtROS), and intracellular cytokines (TNF alpha, IL-10) using flow cytometry. Isolated splenocytes from septic and septic butyrate treated rats were stimulated with LPS for 18 h and the effects of butyrate on cytokine release assessed. Ex vivo, butyrate (1.8 mM) reduced LPS-induced TNF alpha (<i>p</i> = 0.019) and IL-10 (<i>p</i> = 0.001) release by human PBMCs. In septic animals butyrate infusion reduced the respiratory exchange ratio (<i>p</i> < 0.001), consistent with increased fat metabolism. This was associated with a reduction in cardiac output (<i>p</i> = 0.001), and increased lactate (<i>p</i> = 0.031) compared to placebo-treated septic animals (<i>p</i> < 0.05). Butyrate treatment was associated with a reduction in splenocyte basal respiration (<i>p</i> = 0.077), proton leak (<i>p</i> = 0.022), and non-mitochondrial respiration (<i>p</i> = 0.055), and an increase in MMP (<i>p</i> = 0.007) and mtROS (<i>p</i> = 0.027) compared to untreated septic animals. Splenocyte intracellular cytokines were unaffected by butyrate, although LPS-induced IL-10 release was impaired (<i>p</i> = 0.039). In summary, butyrate supplementation exacerbates myocardial and immune cell mitochondrial dysfunction in a rat model of faecal peritonitis.https://www.mdpi.com/2075-1729/12/12/2034sepsisbutyratenutritionfatty acidsimmunitymitochondria |
| spellingShingle | Vera B. M. Peters Nishkantha Arulkumaran Miranda J. Melis Charlotte Gaupp Thierry Roger Manu Shankar-Hari Mervyn Singer Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis Life sepsis butyrate nutrition fatty acids immunity mitochondria |
| title | Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis |
| title_full | Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis |
| title_fullStr | Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis |
| title_full_unstemmed | Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis |
| title_short | Butyrate Supplementation Exacerbates Myocardial and Immune Cell Mitochondrial Dysfunction in a Rat Model of Faecal Peritonitis |
| title_sort | butyrate supplementation exacerbates myocardial and immune cell mitochondrial dysfunction in a rat model of faecal peritonitis |
| topic | sepsis butyrate nutrition fatty acids immunity mitochondria |
| url | https://www.mdpi.com/2075-1729/12/12/2034 |
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