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Published in: Current Nutrition Reports 4/2018

Open Access 01-12-2018 | Cardiovascular Disease (JHY Wu, Section Editor)

Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health

Authors: Edward S. Chambers, Tom Preston, Gary Frost, Douglas J. Morrison

Published in: Current Nutrition Reports | Issue 4/2018

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Abstract

Purpose of this Review

This review assesses the latest evidence linking short-chain fatty acids (SCFA) with host metabolic health and cardiovascular disease (CVD) risk and presents the latest evidence on possible biological mechanisms.

Recent Findings

SCFA have a range of effects locally in the gut and at both splanchnic and peripheral tissues which together appear to induce improved metabolic regulation and have direct and indirect effects on markers of CVD risk.

Summary

SCFA produced primarily from the microbial fermentation of dietary fibre appear to be key mediators of the beneficial effects elicited by the gut microbiome. Not only does dietary fibre fermentation regulate microbial activity in the gut, SCFA also directly modulate host health through a range of tissue-specific mechanisms related to gut barrier function, glucose homeostasis, immunomodulation, appetite regulation and obesity. With the increasing burden of obesity worldwide, the role for gut microbiota-generated SCFA in protecting against the effects of energy dense diets offers an intriguing new avenue for regulating metabolic health and CVD risk.
Literature
4.
go back to reference WHO | Global atlas on cardiovascular disease prevention and control. WHO. 2015. doi:/entity/cardiovascular_diseases/publications/atlas_cvd/en/index.html. WHO | Global atlas on cardiovascular disease prevention and control. WHO. 2015. doi:/entity/cardiovascular_diseases/publications/atlas_cvd/en/index.html.
9.
10.
go back to reference Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc. 2016;5(6). https://doi.org/10.1161/jaha.115.002816. Senthong V, Wang Z, Li XS, Fan Y, Wu Y, Tang WH et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J Am Heart Assoc. 2016;5(6). https://​doi.​org/​10.​1161/​jaha.​115.​002816.
11.
go back to reference Zhu W, Wang Z, Tang WHW, Hazen SL. Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects. Circulation. vol 17. United States2017. p. 1671–1673.CrossRefPubMedPubMedCentral Zhu W, Wang Z, Tang WHW, Hazen SL. Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects. Circulation. vol 17. United States2017. p. 1671–1673.CrossRefPubMedPubMedCentral
12.
go back to reference • Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290(9):5647–60. https://doi.org/10.1074/jbc.M114.618249 The study by Gregory et al (2015) demonstrates that a gut microbiome which produces higher levels of TMAO can be transplanted to replicate atherosclerotic lesions in an antibiotic-treated apolipoprotein e null mouse model. CrossRefPubMed • Gregory JC, Buffa JA, Org E, Wang Z, Levison BS, Zhu W, et al. Transmission of atherosclerosis susceptibility with gut microbial transplantation. J Biol Chem. 2015;290(9):5647–60. https://​doi.​org/​10.​1074/​jbc.​M114.​618249 The study by Gregory et al (2015) demonstrates that a gut microbiome which produces higher levels of TMAO can be transplanted to replicate atherosclerotic lesions in an antibiotic-treated apolipoprotein e null mouse model. CrossRefPubMed
20.
go back to reference •• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63. https://doi.org/10.1038/nature12820 The study by David et al (2014) elegantly demonstrates the rapid change in microbial fermentation patterns and bacterial diversity that are largely driven by dietary inputs reflecting the balance between carbohydrate and protein fermentation by the gut microbiota. CrossRefPubMed •• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559–63. https://​doi.​org/​10.​1038/​nature12820 The study by David et al (2014) elegantly demonstrates the rapid change in microbial fermentation patterns and bacterial diversity that are largely driven by dietary inputs reflecting the balance between carbohydrate and protein fermentation by the gut microbiota. CrossRefPubMed
30.
go back to reference Roshanravan N, Mahdavi R, Alizadeh E, Jafarabadi MA, Hedayati M, Ghavami A, et al. Effect of butyrate and inulin supplementation on glycemic status, lipid profile and glucagon-like peptide 1 level in patients with type 2 diabetes: a randomized double-blind. Placebo-Controlled Trial Horm Metab Res. 2017;49(11):886–91. https://doi.org/10.1055/s-0043-119089.CrossRefPubMed Roshanravan N, Mahdavi R, Alizadeh E, Jafarabadi MA, Hedayati M, Ghavami A, et al. Effect of butyrate and inulin supplementation on glycemic status, lipid profile and glucagon-like peptide 1 level in patients with type 2 diabetes: a randomized double-blind. Placebo-Controlled Trial Horm Metab Res. 2017;49(11):886–91. https://​doi.​org/​10.​1055/​s-0043-119089.CrossRefPubMed
35.
go back to reference • van der Beek CM, Canfora EE, Lenaerts K, Troost FJ, Olde Damink SWM, Holst JJ, et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016;130(22):2073–82. https://doi.org/10.1042/cs20160263 The study by van der Beek (2016) highlights the importance of regional SCFA producton in the gut and that studies using oral versus regional delivery of SCFA need to be interpreted with caution due to the regional and tissue-specific nature of SCFA physiology.CrossRef • van der Beek CM, Canfora EE, Lenaerts K, Troost FJ, Olde Damink SWM, Holst JJ, et al. Distal, not proximal, colonic acetate infusions promote fat oxidation and improve metabolic markers in overweight/obese men. Clin Sci (Lond). 2016;130(22):2073–82. https://​doi.​org/​10.​1042/​cs20160263 The study by van der Beek (2016) highlights the importance of regional SCFA producton in the gut and that studies using oral versus regional delivery of SCFA need to be interpreted with caution due to the regional and tissue-specific nature of SCFA physiology.CrossRef
39.
40.
go back to reference Chambers ES, Byrne CS, Rugyendo A, Morrison DJ, Preston T, Tedford MC, et al. The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes Obes Metab. 2018. https://doi.org/10.1111/dom.13500. Chambers ES, Byrne CS, Rugyendo A, Morrison DJ, Preston T, Tedford MC, et al. The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease. Diabetes Obes Metab. 2018. https://​doi.​org/​10.​1111/​dom.​13500.
48.
go back to reference Reimer RA, Willis HJ, Tunnicliffe JM, Park H, Madsen KL, Soto-Vaca A. Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: a randomized controlled trial. Mol Nutr Food Res. 2017;61(11). https://doi.org/10.1002/mnfr.201700484.CrossRef Reimer RA, Willis HJ, Tunnicliffe JM, Park H, Madsen KL, Soto-Vaca A. Inulin-type fructans and whey protein both modulate appetite but only fructans alter gut microbiota in adults with overweight/obesity: a randomized controlled trial. Mol Nutr Food Res. 2017;61(11). https://​doi.​org/​10.​1002/​mnfr.​201700484.CrossRef
52.
go back to reference Gonzalez A, Krieg R, Massey HD, Carl D, Ghosh S, Gehr TWB, et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant. 2018. https://doi.org/10.1093/ndt/gfy238. Gonzalez A, Krieg R, Massey HD, Carl D, Ghosh S, Gehr TWB, et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant. 2018. https://​doi.​org/​10.​1093/​ndt/​gfy238.
56.
go back to reference Han X, Song H, Wang Y, Sheng Y, Chen J. Sodium butyrate protects the intestinal barrier function in peritonitic mice. Int J Clin Exp Med. 2015;8(3):4000–7.PubMedPubMedCentral Han X, Song H, Wang Y, Sheng Y, Chen J. Sodium butyrate protects the intestinal barrier function in peritonitic mice. Int J Clin Exp Med. 2015;8(3):4000–7.PubMedPubMedCentral
57.
go back to reference Yang F, Wang LK, Li X, Wang LW, Han XQ, Gong ZJ. Sodium butyrate protects against toxin-induced acute liver failure in rats. Hepatobiliary Pancreat Dis Int. 2014;13(3):309–15.CrossRefPubMed Yang F, Wang LK, Li X, Wang LW, Han XQ, Gong ZJ. Sodium butyrate protects against toxin-induced acute liver failure in rats. Hepatobiliary Pancreat Dis Int. 2014;13(3):309–15.CrossRefPubMed
60.
go back to reference • Kim S, Goel R, Kumar A, Qi Y, Lobaton G, Hosaka K, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132(6):701–18. https://doi.org/10.1042/cs20180087 The study by Kim et al (2018) is noteworthy because of the observed association between a range of markers for gut barrier function and blood pressure. Although a causal relationship has not been established in humans, animal model data suggests a key role for the SCFA butyrate.CrossRef • Kim S, Goel R, Kumar A, Qi Y, Lobaton G, Hosaka K, et al. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure. Clin Sci (Lond). 2018;132(6):701–18. https://​doi.​org/​10.​1042/​cs20180087 The study by Kim et al (2018) is noteworthy because of the observed association between a range of markers for gut barrier function and blood pressure. Although a causal relationship has not been established in humans, animal model data suggests a key role for the SCFA butyrate.CrossRef
62.
68.
go back to reference • Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013;110(11):4410–5. https://doi.org/10.1073/pnas.1215927110 The study by Pluznick et al (2013) demonstrated the complex biological regulation of blood pressure through the counter-acting role of SCFA on the receptors Olfr78 and FFAR 3 expressed in renal juxtaglomerular cells and smooth muscle cells in blood vessels. CrossRefPubMedPubMedCentral • Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci U S A. 2013;110(11):4410–5. https://​doi.​org/​10.​1073/​pnas.​1215927110 The study by Pluznick et al (2013) demonstrated the complex biological regulation of blood pressure through the counter-acting role of SCFA on the receptors Olfr78 and FFAR 3 expressed in renal juxtaglomerular cells and smooth muscle cells in blood vessels. CrossRefPubMedPubMedCentral
72.
go back to reference • Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018;359(6382):1376–83. https://doi.org/10.1126/science.aar3318 The study by Thaiss et al (2018) demonstrates the complex system and reciprocol relationships between gut microbial acitivty, SCFA and glucose homeostasis which in turn impacts upon gut barrier function. CrossRefPubMed • Thaiss CA, Levy M, Grosheva I, Zheng D, Soffer E, Blacher E, et al. Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection. Science. 2018;359(6382):1376–83. https://​doi.​org/​10.​1126/​science.​aar3318 The study by Thaiss et al (2018) demonstrates the complex system and reciprocol relationships between gut microbial acitivty, SCFA and glucose homeostasis which in turn impacts upon gut barrier function. CrossRefPubMed
79.
go back to reference den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64(7):2398–408. https://doi.org/10.2337/db14-1213.CrossRef den Besten G, Bleeker A, Gerding A, van Eunen K, Havinga R, van Dijk TH, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARgamma-dependent switch from lipogenesis to fat oxidation. Diabetes. 2015;64(7):2398–408. https://​doi.​org/​10.​2337/​db14-1213.CrossRef
82.
go back to reference Jia Y, Hong J, Li H, Hu Y, Jia L, Cai D, et al. Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation-associated beta3 -adrenergic receptor activation in high-fat diet-induced obese mice. Exp Physiol. 2017;102(2):273–81. https://doi.org/10.1113/ep086114.CrossRefPubMed Jia Y, Hong J, Li H, Hu Y, Jia L, Cai D, et al. Butyrate stimulates adipose lipolysis and mitochondrial oxidative phosphorylation through histone hyperacetylation-associated beta3 -adrenergic receptor activation in high-fat diet-induced obese mice. Exp Physiol. 2017;102(2):273–81. https://​doi.​org/​10.​1113/​ep086114.CrossRefPubMed
88.
go back to reference • Marino E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18(5):552–62. https://doi.org/10.1038/ni.3713 The study by Marino et al (2017) demonstrates the importance of regional modulation of SCFA production in the gut on conditioning immune cell response in a non-obese diabetic mouse strain to protect against diabetes. CrossRefPubMed • Marino E, Richards JL, McLeod KH, Stanley D, Yap YA, Knight J, et al. Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes. Nat Immunol. 2017;18(5):552–62. https://​doi.​org/​10.​1038/​ni.​3713 The study by Marino et al (2017) demonstrates the importance of regional modulation of SCFA production in the gut on conditioning immune cell response in a non-obese diabetic mouse strain to protect against diabetes. CrossRefPubMed
Metadata
Title
Role of Gut Microbiota-Generated Short-Chain Fatty Acids in Metabolic and Cardiovascular Health
Authors
Edward S. Chambers
Tom Preston
Gary Frost
Douglas J. Morrison
Publication date
01-12-2018
Publisher
Springer US
Published in
Current Nutrition Reports / Issue 4/2018
Electronic ISSN: 2161-3311
DOI
https://doi.org/10.1007/s13668-018-0248-8

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