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Gut Microbiota-Derived Short-Chain Fatty Acids Facilitate Microbiota:Host Cross talk and Modulate Obesity and Hypertension

  • Gut Microbiome and Hypertension (J Ferguson, Section Editor)
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Abstract

Purpose of Review

The purpose of this review is to summarize the evidence supporting a role of short-chain fatty acids (SCFAs) as messengers facilitating cross talk between the host and gut microbiota and discuss the effects of altered SCFA signaling in obesity and hypertension.

Recent Findings

Recent evidence suggests there to be a significant contribution of gut microbiota-derived SCFAs to microbe:host communication and host metabolism. SCFA production within the intestine modulates intestinal pH, microbial composition, and intestinal barrier integrity. SCFA signaling through host receptors, such as PPARγ and GPCRs, modulates host health and disease physiology. Alterations in SCFA signaling and downstream effects on inflammation are implicated in the development of obesity and hypertension.

Summary

SCFAs are crucial components of the holobiont relationship; in the proper environment, they support normal gut, immune, and metabolic function. Dysregulation of microbial SCFA signaling affects downstream host metabolism, with implications in obesity and hypertension.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. van de Guchte M, Blottière HM, Doré J. Humans as holobionts: implications for prevention and therapy. Microbiome. 2018;6:81.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Barone M, Turroni S, Rampelli S, Soverini M, D’Amico F, Biagi E, et al. Gut microbiome response to a modern Paleolithic diet in a Western lifestyle context. Loor JJ, editor. PLoS One. 2019;14:e0220619.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    Article  PubMed  Google Scholar 

  4. Zinöcker M, Lindseth I. The Western diet–microbiome-host interaction and its role in metabolic disease. Nutrients. 2018;10:365.

    Article  PubMed Central  CAS  Google Scholar 

  5. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos NA, Donus C, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity. 2010;18:190–5.

  6. de la Cuesta-Zuluaga J, Mueller N, Álvarez-Quintero R, Velásquez-Mejía E, Sierra J, Corrales-Agudelo V, et al. Higher fecal short-chain fatty acid levels are associated with gut microbiome dysbiosis, obesity, hypertension and cardiometabolic disease risk factors. Nutrients. 2018;11:51.

    Article  PubMed Central  CAS  Google Scholar 

  7. Wolfe BE, Dutton RJ. Fermented foods as experimentally tractable microbial ecosystems. Cell. 2015;161:49–55.

    Article  CAS  PubMed  Google Scholar 

  8. den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013;54:2325–40.

    Article  CAS  Google Scholar 

  9. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1–8.

    Article  CAS  PubMed  Google Scholar 

  10. Rivière A, Selak M, Lantin D, Leroy F, De Vuyst L. Bifidobacteria and butyrate-producing colon bacteria: importance and strategies for their stimulation in the human gut. Front Microbiol [Internet]. 2016 [cited 2020 Sep 4];7. Available from: http://journal.frontiersin.org/Article/10.3389/fmicb.2016.00979/abstract

  11. Belenguer A, Duncan SH, Calder AG, Holtrop G, Louis P, Lobley GE, et al. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl Environ Microbiol. 2006;72:3593–9.

  12. 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;505:559–63.

  13. Wu GD, Compher C, Chen EZ, Smith SA, Shah RD, Bittinger K, et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 2016;65:63–72.

  14. Wu GD, Chen J, Hoffmann C, Bittinger K, Chen Y-Y, Keilbaugh SA, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8.

  15. Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H. Evaluating causality of gut microbiota in obesity and diabetes in humans. Endocr Rev. 2018;39:133–53.

    Article  PubMed  Google Scholar 

  16. Walker AW, Ince J, Duncan SH, Webster LM, Holtrop G, Ze X, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011;5:220–30.

  17. Dominika Ś, Arjan N, Karyn RP, Henryk K. The study on the impact of glycated pea proteins on human intestinal bacteria. Int J Food Microbiol. 2011;145:267–72.

    Article  CAS  PubMed  Google Scholar 

  18. Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016;529:212–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mayengbam S, Lambert JE, Parnell JA, Tunnicliffe JM, Nicolucci AC, Han J, et al. Impact of dietary fiber supplementation on modulating microbiota–host–metabolic axes in obesity. J Nutr Biochem. 2019;64:228–36.

  20. Reimer RA, Soto-Vaca A, Nicolucci AC, Mayengbam S, Park H, Madsen KL, et al. Effect of chicory inulin-type fructan–containing snack bars on the human gut microbiota in low dietary fiber consumers in a randomized crossover trial. Am J Clin Nutr. 2020;111:1286–96.

  21. Fava F, Gitau R, Griffin BA, Gibson GR, Tuohy KM, Lovegrove JA. The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome ‘at-risk’ population. Int J Obes. 2013;37:216–23.

    Article  CAS  Google Scholar 

  22. Wan Y, Tong W, Zhou R, Li J, Yuan J, Wang F, et al. Habitual animal fat consumption in shaping gut microbiota and microbial metabolites. Food Funct. 2019;10:7973–82.

  23. Singh RK, Chang H-W, Yan D, Lee KM, Ucmak D, Wong K, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017;15:73.

  24. De Filippo C, Cavalieri D, Di Paola M, Ramazzotti M, Poullet JB, Massart S, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci. 2010;107:14691–6.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Saffouri GB, Shields-Cutler RR, Chen J, Yang Y, Lekatz HR, Hale VL, et al. Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders. Nat Commun. 2019;10:2012.

  26. Sasaki K, Sasaki D, Hannya A, Tsubota J, Kondo A. In vitro human colonic microbiota utilises D-β-hydroxybutyrate to increase butyrogenesis. Sci Rep. 2020;10:8516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. ANR MicroObes consortium, ANR MicroObes consortium members, Cotillard A, Kennedy SP, Kong LC, Prifti E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–588.

  28. Balamurugan R, Pugazhendhi S, Balachander GM, Dharmalingam T, Mortimer EK, Gopalsamy GL, et al. Effect of native and acetylated dietary resistant starches on intestinal fermentative capacity of normal and stunted children in Southern India. Int J Environ Res Public Health. 2019;16:3922.

  29. Kovatcheva-Datchary P, Nilsson A, Akrami R, Lee YS, De Vadder F, Arora T, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella. Cell Metab. 2015;22:971–82.

    Article  CAS  PubMed  Google Scholar 

  30. Miller LM, Lampe JW, Newton KM, Gundersen G, Fuller S, Reed SD, et al. Being overweight or obese is associated with harboring a gut microbial community not capable of metabolizing the soy isoflavone daidzein to O- desmethylangolensin in peri- and post-menopausal women. Maturitas. 2017;99:37–42.

    Article  CAS  PubMed  Google Scholar 

  31. Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079–94.

  32. Bennet SMP, Böhn L, Störsrud S, Liljebo T, Collin L, Lindfors P, et al. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut. 2018;67:872–81.

  33. Korpela K, Flint HJ, Johnstone AM, Lappi J, Poutanen K, Dewulf E, et al. Gut microbiota signatures predict host and microbiota responses to dietary interventions in obese individuals. Bereswill S, editor. PLoS One. 2014;9:e90702.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Li Q, Chang Y, Zhang K, Chen H, Tao S, Zhang Z. Implication of the gut microbiome composition of type 2 diabetic patients from northern China. Sci Rep. 2020;10:5450.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Thaiss CA, Itav S, Rothschild D, Meijer MT, Levy M, Moresi C, et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016;540:544–51.

  36. •• Deehan EC, Yang C, Perez-Muñoz ME, Nguyen NK, Cheng CC, Triador L, et al. Precision microbiome modulation with discrete dietary fiber structures directs short-chain fatty acid production. Cell Host Microbe. 2020;27:389–404.e6 This study uses specialized structures of resistant starches to precisely, predictably, and dose-dependently modulate human gut microbial composition and metabolites produced, demonstrating a targeted and personalized nutritional approach to altering the gut microbiome.

    Article  CAS  PubMed  Google Scholar 

  37. Blaak EE, Canfora EE, Theis S, Frost G, Groen AK, Mithieux G, et al. Short chain fatty acids in human gut and metabolic health. Benefic Microbes. 2020;11:411–55.

  38. Litvak Y, Byndloss MX, Bäumler AJ. Colonocyte metabolism shapes the gut microbiota. Science. 2018;362:eaat9076.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Schönfeld P, Wojtczak L. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective. J Lipid Res. 2016;57:943–54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Sivaprakasam S, Bhutia YD, Yang S, Ganapathy V. Short-chain fatty acid transporters: role in colonic homeostasis. In: Terjung R, editor. Compr Physiol [Internet]. Hoboken, NJ, USA: John Wiley & Sons, Inc.; 2017 [cited 2020 Aug 27]. p. 299–314. Available from: http://doi.wiley.com/10.1002/cphy.c170014

  41. Villodre Tudela C, Boudry C, Stumpff F, Aschenbach JR, Vahjen W, Zentek J, et al. Down-regulation of monocarboxylate transporter 1 (MCT1) gene expression in the colon of piglets is linked to bacterial protein fermentation and pro-inflammatory cytokine-mediated signalling. Br J Nutr. 2015;113:610–7.

  42. Thibault R, De Coppet P, Daly K, Bourreille A, Cuff M, Bonnet C, et al. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007;133:1916–27.

    Article  CAS  PubMed  Google Scholar 

  43. Ferrer-Picón E, Dotti I, Corraliza AM, Mayorgas A, Esteller M, Perales JC, et al. Intestinal inflammation modulates the epithelial response to butyrate in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2020;26:43–55.

  44. Boets E, Gomand SV, Deroover L, Preston T, Vermeulen K, De Preter V, et al. Systemic availability and metabolism of colonic-derived short-chain fatty acids in healthy subjects: a stable isotope study: short-chain fatty acid systemic availability and metabolism in humans. J Physiol. 2017;595:541–55.

    Article  CAS  PubMed  Google Scholar 

  45. Bloemen JG, Venema K, van de Poll MC, Olde Damink SW, Buurman WA, Dejong CH. Short chain fatty acids exchange across the gut and liver in humans measured at surgery. Clin Nutr. 2009;28:657–61.

    Article  CAS  PubMed  Google Scholar 

  46. van der Beek CM, Bloemen JG, van den Broek MA, Lenaerts K, Venema K, Buurman WA, et al. Hepatic uptake of rectally administered butyrate prevents an increase in systemic butyrate concentrations in humans. J Nutr. 2015;145:2019–24.

  47. Müller M, Hernández MAG, Goossens GH, Reijnders D, Holst JJ, Jocken JWE, et al. Circulating but not faecal short-chain fatty acids are related to insulin sensitivity, lipolysis and GLP-1 concentrations in humans. Sci Rep. 2019;9:12515.

  48. Perry RJ, Peng L, Barry NA, Cline GW, Zhang D, Cardone RL, et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature. 2016;534:213–7.

  49. Burger-van Paassen N, Vincent A, Puiman PJ, van der Sluis M, Bouma J, Boehm G, et al. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection. Biochem J. 2009;420:211–9.

  50. Gaudier E, Jarry A, Blottière HM, de Coppet P, Buisine MP, Aubert JP, et al. Butyrate specifically modulates MUC gene expression in intestinal epithelial goblet cells deprived of glucose. Am J Physiol-Gastrointest Liver Physiol. 2004;287:G1168–74.

  51. Hansson GC. Role of mucus layers in gut infection and inflammation. Curr Opin Microbiol. 2012;15:57–62.

    Article  CAS  PubMed  Google Scholar 

  52. Cornick S, Tawiah A, Chadee K. Roles and regulation of the mucus barrier in the gut. Tissue Barriers. 2015;3:e982426.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Kim S, Kim J-H, Park BO, Kwak YS. Perspectives on the therapeutic potential of short-chain fatty acid receptors. BMB Rep. 2014;47:173–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Thangaraju M, Cresci GA, Liu K, Ananth S, Gnanaprakasam JP, Browning DD, et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009;69:2826–32.

  55. Chen X-F, Chen X, Tang X. Short-chain fatty acid, acylation and cardiovascular diseases. Clin Sci. 2020;134:657–76.

    Article  CAS  Google Scholar 

  56. Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MAR. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol. 2016;5:e73.

    Article  CAS  Google Scholar 

  57. •• Kimura I, Miyamoto J, Ohue-Kitano R, Watanabe K, Yamada T, Onuki M, et al. Maternal gut microbiota in pregnancy influences offspring metabolic phenotype in mice. Science. 2020;367:eaaw8429. Describes the multi-generational effects of SCFA signaling on offspring metabolic and neural development.

  58. Wächtershäuser A, Loitsch SM, Stein J. PPAR-γ is selectively upregulated in Caco-2 cells by butyrate. Biochem Biophys Res Commun. 2000;272:380–5.

    Article  PubMed  CAS  Google Scholar 

  59. Alex S, Lange K, Amolo T, Grinstead JS, Haakonsson AK, Szalowska E, et al. Short-chain fatty acids stimulate angiopoietin-like 4 synthesis in human colon adenocarcinoma cells by activating peroxisome proliferator-activated receptor. Mol Cell Biol. 2013;33:1303–16.

  60. Zeitouni NE, Chotikatum S, von Köckritz-Blickwede M, Naim HY. The impact of hypoxia on intestinal epithelial cell functions: consequences for invasion by bacterial pathogens. Mol Cell Pediatr. 2016;3:14.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Bach Knudsen K, Lærke H, Hedemann M, Nielsen T, Ingerslev A, Gundelund Nielsen D, et al. Impact of diet-modulated butyrate production on intestinal barrier function and inflammation. Nutrients. 2018;10:1499.

  62. Kelly CJ, Zheng L, Campbell EL, Saeedi B, Scholz CC, Bayless AJ, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17:662–71.

  63. Shulzhenko N, Morgun A, Hsiao W, Battle M, Yao M, Gavrilova O, et al. Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut. Nat Med. 2011;17:1585–93.

  64. Byndloss MX, Olsan EE, Rivera-Chávez F, Tiffany CR, Cevallos SA, Lokken KL, et al. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science. 2017;357:570–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Schwab M, Reynders V, Loitsch S, Steinhilber D, Stein J, Schröder O. Involvement of different nuclear hormone receptors in butyrate-mediated inhibition of inducible NFκB signalling. Mol Immunol. 2007;44:3625–32.

    Article  CAS  PubMed  Google Scholar 

  66. Lupp C, Robertson ML, Wickham ME, Sekirov I, Champion OL, Gaynor EC, et al. Host-mediated inflammation disrupts the intestinal microbiota and promotes the overgrowth of Enterobacteriaceae. Cell Host Microbe. 2007;2:119–29.

  67. Satokari R. High intake of sugar and the balance between pro- and anti-inflammatory gut bacteria. Nutrients. 2020;12:1348.

    Article  CAS  PubMed Central  Google Scholar 

  68. Rousseaux C, El-Jamal N, Fumery M, Dubuquoy C, Romano O, Chatelain D, et al. The 5-aminosalicylic acid antineoplastic effect in the intestine is mediated by PPARγ. Carcinogenesis. 2013;34:2580–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Peyrin-Biroulet L, Beisner J, Wang G, Nuding S, Oommen ST, Kelly D, et al. Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon. Proc Natl Acad Sci. 2010;107:8772–7.

  70. Ponferrada Á, Caso JR, Alou L, Colón A, Sevillano D, Moro MA, et al. The role of PPARγ on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction. Gastroenterology. 2007;132:1791–803.

  71. Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiol. 2017;17:120.

  72. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci. 2005;102:11070–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mathur R, Barlow GM. Obesity and the microbiome. Expert Rev Gastroenterol Hepatol. 2015;9:1087–99.

    Article  CAS  PubMed  Google Scholar 

  74. Miranda VPN, dos Santos Amorim PR, Bastos RR, de Faria ER, de Castro Moreira ME, do Carmo Castro Franceschini S, et al. Abundance of gut microbiota, concentration of short-chain fatty acids, and inflammatory markers associated with elevated body fat, overweight, and obesity in female adolescents. Mediat Inflamm. 2019;2019:1–11.

    Article  CAS  Google Scholar 

  75. Crovesy L, Masterson D, Rosado EL. Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr. 2020;74:1251–62.

    Article  PubMed  Google Scholar 

  76. Walters WA, Xu Z, Knight R. Meta-analyses of human gut microbes associated with obesity and IBD. FEBS Lett. 2014;588:4223–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ley RE. Prevotella in the gut: choose carefully. Nat Rev Gastroenterol Hepatol. 2016;13:69–70.

    Article  CAS  PubMed  Google Scholar 

  78. Bäckhed F, Manchester JK, Semenkovich CF, Gordon JI. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci. 2007;104:979–84.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  79. Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science. 2013;341:1241214–4.

  80. Byrne CS, Chambers ES, Morrison DJ, Frost G. The role of short chain fatty acids in appetite regulation and energy homeostasis. Int J Obes. 2015;39:1331–8.

    Article  CAS  Google Scholar 

  81. Arencibia-Albite F. Serious analytical inconsistencies challenge the validity of the energy balance theory. Heliyon. 2020;6:e04204.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Al-Lahham SH, Roelofsen H, Priebe M, Weening D, Dijkstra M, Hoek A, et al. Regulation of adipokine production in human adipose tissue by propionic acid. Eur J Clin Investig. 2010;40:401–7.

    Article  CAS  Google Scholar 

  83. Yao H, Fan C, Fan X, Lu Y, Wang Y, Wang R, et al. Effects of gut microbiota on leptin expression and body weight are lessened by high-fat diet in mice. Br J Nutr. 2020;124:396–406.

  84. Yao H, Fan C, Lu Y, Fan X, Xia L, Li P, et al. Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice. Genes Nutr. 2020;15:12.

  85. Larraufie P, Martin-Gallausiaux C, Lapaque N, Dore J, Gribble FM, Reimann F, et al. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci Rep. 2018;8:74.

  86. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2012;61:364–71.

  87. Fernandes J, Su W, Rahat-Rozenbloom S, Wolever TMS, Comelli EM. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans. Nutr Diabetes. 2014;4:e121–1.

  88. Kim KN, Yao Y, Ju SY. Short chain fatty acids and fecal microbiota abundance in humans with obesity: a systematic review and meta-analysis. Nutrients. 2019;11:2512.

    Article  CAS  PubMed Central  Google Scholar 

  89. Chambers ES, Byrne CS, Aspey K, Chen Y, Khan S, Morrison DJ, et al. Acute oral sodium propionate supplementation raises resting energy expenditure and lipid oxidation in fasted humans. Diabetes Obes Metab. 2018;20:1034–9.

  90. Canfora EE, van der Beek CM, Jocken JWE, Goossens GH, Holst JJ, Olde Damink SWM, et al. Colonic infusions of short-chain fatty acid mixtures promote energy metabolism in overweight/obese men: a randomized crossover trial. Sci Rep. 2017;7:2360.

  91. 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. 2016;130:2073–82.

  92. Canfora EE, Jocken JW, Blaak EE. Short-chain fatty acids in control of body weight and insulin sensitivity. Nat Rev Endocrinol. 2015;11:577–91.

    Article  CAS  PubMed  Google Scholar 

  93. Aleixandre A, Miguel M. Dietary fiber and blood pressure control. Food Funct. 2016;7:1864–71.

    Article  CAS  PubMed  Google Scholar 

  94. 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. 2018;132:701–18.

  95. Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, et al. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome. 2017;5:14.

  96. Gomez-Arango LF, Barrett HL, McIntyre HD, Callaway LK, Morrison M, Dekker NM. Increased systolic and diastolic blood pressure is associated with altered gut microbiota composition and butyrate production in early pregnancy. Hypertension. 2016;68:974–81.

    Article  CAS  PubMed  Google Scholar 

  97. •• Verhaar BJH, Collard D, Prodan A, Levels JHM, Zwinderman AH, Bäckhed F, et al. Associations between gut microbiota, faecal short-chain fatty acids, and blood pressure across ethnic groups: the HELIUS study. Eur Heart J. 2020:ehaa704 This paper demonstrated a population- and ethnic-specific association of the fecal microbiota composition in a direct association with blood pressure as SCFA-producing bacteria and plasma SCFA levels were inversely proportional to blood pressure while fecal SCFA content was positively associated with blood pressure.

  98. • Chang Y, Chen Y, Zhou Q, Wang C, Chen L, Di W, et al. Short-chain fatty acids accompanying changes in the gut microbiome contribute to the development of hypertension in patients with preeclampsia. Clin Sci. 2020;134:289–302 This study observed diminished microbial diversity and richness, reduced butyrate producers and abundance, and prominent intestinal inflammation and permeability in a population of pregnant women diagnosed with preeclampsia.

    Article  CAS  Google Scholar 

  99. Galla S, Chakraborty S, Cheng X, Yeo J, Mell B, Zhang H, et al. Disparate effects of antibiotics on hypertension. Physiol Genomics. 2018;50:837–45.

  100. Jose PA, Raj D. Gut microbiota in hypertension. Curr Opin Nephrol Hypertens. 2015;24:403–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. •• Calderón-Pérez L, Gosalbes MJ, Yuste S, Valls RM, Pedret A, Llauradó E, et al. Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study. Sci Rep. 2020;10:6436 Study characterized the fecal SCFA and microbial profiles which were specific to and regarded as a signature for individuals with HTN prior to drug therapy.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, et al. Role of the gut microbiome in obstructive sleep apnea–induced hypertension. Hypertension. 2016;67:469–74.

  103. Toral M, Robles-Vera I, Visitación N, Romero M, Sánchez M, Gómez-Guzmán M, et al. Role of the immune system in vascular function and blood pressure control induced by faecal microbiota transplantation in rats. Acta Physiol. 2019:e13285.

  104. Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan RM, et al. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics. 2017;49:96–104.

    Article  CAS  PubMed  Google Scholar 

  105. Yan X, Jin J, Su X, Yin X, Gao J, Wang X, et al. Intestinal Flora modulates blood pressure by regulating the synthesis of intestinal-derived corticosterone in high salt-induced hypertension. Circ Res. 2020;126:839–53.

  106. Huart J, Leenders J, Taminiau B, Descy J, Saint-Remy A, Daube G, et al. Gut microbiota and fecal levels of short-chain fatty acids differ upon 24-hour blood pressure levels in men. Hypertension. 2019;74:1005–13.

  107. Chakraborty S, Mandal J, Cheng X, Galla S, Hindupur A, Saha P, et al. Diurnal timing dependent alterations in gut microbial composition are synchronously linked to salt-sensitive hypertension and renal damage. Hypertension. 2020;76:59–72.

  108. Mashaqi S, Gozal D. Obstructive sleep apnea and systemic hypertension: gut dysbiosis as the mediator? J Clin Sleep Med. 2019;15:1517–27.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Liu J, Li T, Wu H, Shi H, Bai J, Zhao W, et al. Lactobacillus rhamnosus GG strain mitigated the development of obstructive sleep apnea-induced hypertension in a high salt diet via regulating TMAO level and CD4+ T cell induced-type I inflammation. Biomed Pharmacother. 2019;112:108580.

  110. Ganesh BP, Nelson JW, Eskew JR, Ganesan A, Ajami NJ, Petrosino JF, et al. Prebiotics, probiotics, and acetate supplementation prevent hypertension in a model of obstructive sleep apnea. Hypertension. 2018;72:1141–50.

  111. Dave LA, Hayes M, Montoya CA, Rutherfurd SM, Moughan PJ. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides. Peptides. 2016;76:30–44.

    Article  CAS  PubMed  Google Scholar 

  112. Richards EM, Pepine CJ, Raizada MK, Kim S. The gut, its microbiome, and hypertension. Curr Hypertens Rep. 2017;19:36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. 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. 2013;110:4410–5.

  114. Miyamoto J, Kasubuchi M, Nakajima A, Irie J, Itoh H, Kimura I. The role of short-chain fatty acid on blood pressure regulation. Curr Opin Nephrol Hypertens. 2016;25:379–83.

    Article  CAS  PubMed  Google Scholar 

  115. Bartolomaeus H, Balogh A, Yakoub M, Homann S, Markó L, Höges S, et al. Short-chain fatty acid propionate protects from hypertensive cardiovascular damage. Circulation. 2019;139:1407–21.

  116. Felizardo RJF, Watanabe IKM, Dardi P, Rossoni LV, Câmara NOS. The interplay among gut microbiota, hypertension and kidney diseases: the role of short-chain fatty acids. Pharmacol Res. 2019;141:366–77.

    Article  CAS  PubMed  Google Scholar 

  117. Marques FZ, Nelson E, Chu P-Y, Horlock D, Fiedler A, Ziemann M, et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation. 2017;135:964–77.

  118. Hsu C-N, Lin Y-J, Hou C-Y, Tain Y-L. Maternal administration of probiotic or prebiotic prevents male adult rat offspring against developmental programming of hypertension induced by high fructose consumption in pregnancy and lactation. Nutrients. 2018;10:1229.

    Article  PubMed Central  CAS  Google Scholar 

  119. Hsu C-N, Hou C-Y, Chan JYH, Lee C-T, Tain Y-L. Hypertension programmed by perinatal high-fat diet: effect of maternal gut microbiota-targeted therapy. Nutrients. 2019;11:2908.

    Article  PubMed Central  Google Scholar 

  120. Na L, Chu X, Jiang S, Li C, Li G, He Y, et al. Vinegar decreases blood pressure by down-regulating AT1R expression via the AMPK/PGC-1α/PPARγ pathway in spontaneously hypertensive rats. Eur J Nutr. 2016;55:1245–53.

  121. Hsu C, Chang-Chien G, Lin S, Hou C, Tain Y. Targeting on gut microbial metabolite trimethylamine-N-oxide and short-chain fatty acid to prevent maternal high-fructose-diet-induced developmental programming of hypertension in adult male offspring. Mol Nutr Food Res. 2019;63:1900073.

    Article  CAS  Google Scholar 

  122. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. Moran MA, editor. mBio. 2014;5:e00889–14.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank Katie Meyer for her review and suggestions for the manuscript.

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This work was supported by funding from the Layton Family Fund, and by R01DK117144.

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Overby, H.B., Ferguson, J.F. Gut Microbiota-Derived Short-Chain Fatty Acids Facilitate Microbiota:Host Cross talk and Modulate Obesity and Hypertension. Curr Hypertens Rep 23, 8 (2021). https://doi.org/10.1007/s11906-020-01125-2

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