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Current Nutrition Reports

24-04-2024 | Hypertension | REVIEW

Management of Cardiovascular Diseases by Short-Chain Fatty Acid Postbiotics

Authors: Seyed Sadeq Mousavi Ghahfarrokhi, Mohamadsadegh Mohamadzadeh, Nasrin Samadi, Mohammad Reza Fazeli, Sara Khaki, Bahman Khameneh, Ramin Khameneh Bagheri

Published in: Current Nutrition Reports

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Abstract

Purpose of Review

Global health concerns persist in the realm of cardiovascular diseases (CVDs), necessitating innovative strategies for both prevention and treatment. This narrative review aims to explore the potential of short-chain fatty acids (SCFAs)—namely, acetate, propionate, and butyrate—as agents in the realm of postbiotics for the management of CVDs.

Recent Findings

We commence our discussion by elucidating the concept of postbiotics and their pivotal significance in mitigating various aspects of cardiovascular diseases. This review centers on a comprehensive examination of diverse SCFAs and their associated receptors, notably GPR41, GPR43, and GPR109a. In addition, we delve into the intricate cellular and pharmacological mechanisms through which these receptors operate, providing insights into their specific roles in managing cardiovascular conditions such as hypertension, atherosclerosis, heart failure, and stroke.

Summary

The integration of current information in our analysis highlights the potential of both SCFAs and their receptors as a promising path for innovative therapeutic approaches in the field of cardiovascular health. The idea of postbiotics arises as an optimistic and inventive method, presenting new opportunities for preventing and treating cardiovascular diseases.
Literature
1.
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol England. 2014;11:506–14.CrossRef
2.
Cuevas-González PF, Liceaga AM, Aguilar-Toalá JE. Postbiotics and paraprobiotics: from concepts to applications Food Res Int. Food Res Int Canada. 2020;136:109502.CrossRef
3.
Kianmehr S, Jahani M, Moazzen N, Ahanchian H, Khameneh B. The potential of probiotics for treating skin disorders: a concise review. Curr Pharm Biotechnol Netherlands. 2022;23:1851–63.CrossRef
4.
5.
Vinderola G, Sanders ME, Salminen S, Szajewska H. Postbiotics: the concept and their use in healthy populations. Front Nutr. 2022;9:1–7.CrossRef
6.
Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol Springer, US. 2021;18:649–67.CrossRef
7.
Vinderola G, Sanders ME, Salminen S. The concept of postbiotics Foods. 2022;11:1–10.
8.
Zhang M, Liang J, Yang Y, Liang H, Jia H, Li D. Current trends of targeted drug delivery for oral cancer therapy. Front Bioeng Biotechnol. 2020;8:1–11.CrossRef
9.
Shoaib M, Shehzad A, Omar M, Rakha A, Raza H, Sharif HR, et al. Inulin: properties, health benefits and food applications. Carbohydr Polym England. 2016;147:444–54.CrossRef
10.
Ashraf R, Shah NP. Immune system stimulation by probiotic microorganisms. Crit Rev Food Sci Nutr United States. 2014;54:938–56.CrossRef
11.
Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Expert consensus document: the International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–14.PubMedCrossRef
12.
Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol England. 2017;14:491–502.CrossRef
13.
Palaria A, Johnson-Kanda I, O’Sullivan DJ. Effect of a synbiotic yogurt on levels of fecal bifidobacteria, clostridia, andenterobacteria. Appl Environ Microbiol. 2012;78:933–40.PubMedPubMedCentralCrossRef
14.
Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med United States. 2019;25:1096–103.CrossRef
15.
Meier T, Gräfe K, Senn F, Sur P, Stangl GI, Dawczynski C, et al. Cardiovascular mortality attributable to dietary risk factors in 51 countries in the WHO European Region from 1990 to 2016: a systematic analysis of the Global Burden of Disease Study. Eur J Epidemiol. 2019;34:37–55.PubMedCrossRef
16.
Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol United States. 2020;76:2982–3021.CrossRef
17.
Banerjee A. Macroeconomics and cardiovascular risk factors: the same view through a differentlens? Circulation. 2013;217:1451–2.CrossRef
18.
Naseri P, Amiri P, Masihay-Akbar H, Jalali-Farahani S, Khalili D, Azizi F. Long-term incidence of cardiovascular outcomes in the middle-aged and elderly with different patterns of physical activity: Tehran lipid and glucose study. BMC Public Health BMC Public Health. 2020;20:1–10.
19.
Keihanian F, Saeidinia A, Bagheri RK, Johnston TP, Sahebkar A. Curcumin, hemostasis, thrombosis, and coagulation. J Cell Physiol United States. 2018;233:4497–511.CrossRef
20.
Khameneh Bagheri R, Najafi MN, Ahmadi M, Saberi M, Maleki M, Baradaran RV. Investigation of the association between serum uric acid levels and HEART risk score in patients with acute coronary syndrome. Physiol Rep. 2022;10:2–9.CrossRef
21.
Saeidinia A, Keihanian F, Butler AE, Bagheri RK, Atkin SL, Sahebkar A. Curcumin in heart failure: a choice for complementary therapy? Pharmacol Res Netherlands. 2018;131:112–9.
22.
Amini M, Zayeri F, Salehi M. Trend analysis of cardiovascular disease mortality, incidence, and mortality-to-incidence ratio: results from Global Burden of Disease Study 2017. BMC Public Health BMC Public Health. 2021;21:1–12.
23.
24.
Iso H. Cardiovascular disease, a major global burden: Epidemiology of stroke andischemic heart disease in Japan. Glob Heal Med. 2021;3:358–64.CrossRef
25.
Daviglus ML, Talavera GA, Avilés-Santa ML, Allison M, Cai J, Criqui MH, et al. Prevalence of major cardiovascular risk factors and cardiovascular diseases among Hispanic/Latino individuals of diverse backgrounds in the United States. JAMA United States. 2012;308:1775–84.
26.
Münzel T, Hahad O, Sørensen M, Lelieveld J, Duerr GD, Nieuwenhuijsen M, et al. Environmental risk factors and cardiovascular diseases: a comprehensive expert review. Cardiovasc Res. 2022;118:2880–902.PubMedCrossRef
27.
Yusuf S, Reddy S, Ounpuu S, Anand S. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation United States. 2001;104:2746–53.CrossRef
28.
Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update a report from the American Heart Association. Circulation Lippincott Williams and Wilkins. 2020;141:E139–596.
29.
Elstrott B, Khan L, Olson S, Raghunathan V, DeLoughery T, Shatzel JJ. The role of iron repletion in adult iron deficiency anemia and other diseases. Eur J Haematol England. 2020;104:153–61.CrossRef
30.
Samadian F, Dalili N, Jamalian A. Lifestyle modifications to prevent and control hypertension. Iran J Kidney Dis Iran. 2016;10:237–63.
31.
Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, Coker TR, et al. Vitamin, mineral, and multivitamin supplementation to prevent cardiovascular disease and cancer: US Preventive Services Task Force Recommendation Statement. JAMA United States. 2022;327:2326–33.
32.
Wierzejska R. Caffeine—common ingredient in a diet and its influence on human health. Rocz Panstw Zakl Hig Poland. 2012;63:141–7.
33.
McCarty MF. Nutraceutical, dietary, and lifestyle options for prevention and treatment of ventricular hypertrophy and heart failure. Int J Mol Sci. 2021;22:1–47.CrossRef
34.
Romero M, Duarte J. Probiotics and prebiotics in cardiovascular diseases. Nutrients. 2023;15:3–6.CrossRef
35.
Divella R, Daniele A, Savino E, Paradiso A. Anticancer effects of nutraceuticals in the Mediterranean diet: an epigenetic diet model. Cancer Genomics Proteomics Greece. 2020;17:335–50.CrossRef
36.
Tang WHW, Bäckhed F, Landmesser U, Hazen SL. Intestinal microbiota in cardiovascular health and disease: JACC state-of-the-art review. J Am Coll Cardiol United States. 2019;73:2089–105.CrossRef
37.
Tang WHW, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res United States. 2017;120:1183–96.CrossRef
38.
Cheng HM, Koutsidis G, Lodge JK, Ashor A, Siervo M, Lara J. Tomato and lycopene supplementation and cardiovascular risk factors: a systematic review and meta-analysis. Atherosclerosis Ireland. 2017;257:100–8.CrossRef
39.
Pahumunto N, Duangnumsawang Y, Teanpaisan R. Effects of potential probiotics on the expression of cytokines and human β-defensins in human gingival epithelial cells and in vivo efficacy in a dog model. Arch Oral Bio England. 2022;142:105513.CrossRef
40.
Xu T, He X, Chen T. Editorial: The role of probiotics, postbiotics, and microbial metabolites in preventing and treating chronic diseases. Front Cell Infect Microbiol. 2023;13:1–2.CrossRef
41.
Żółkiewicz J, Marzec A, Ruszczyński M, Feleszko W. Postbiotics-a step beyond pre- and probiotics. Nutrients. 2020;12:1–17.CrossRef
42.
Uebanso T, Shimohata T, Mawatari K, Takahashi A. Functional roles of B-vitamins in the gut and gut microbiome Mol Nutr Food Res. Mol Nutr Food Res Germany. 2020;64:e2000426.CrossRef
43.
Mosegaard S, Dipace G, Bross P, Carlsen J, Gregersen N, Olsen RKJ. Riboflavin deficiency—implications for general human health and inborn errors of metabolism. Int J Mol Sci. 2020;21:1–26.CrossRef
44.
Anhê FF, Jensen BAH, Perazza LR, Tchernof A, Schertzer JD, Marette A. Bacterial postbiotics as promising tools to mitigate cardiometabolic diseases. J Lipid Atheroscler. 2021;10:123–9.PubMedPubMedCentralCrossRef
45.
•• Lu Y, Zhang Y, Zhao X, Shang C, Xiang M, Li L, et al. Microbiota-derived short-chain fatty acids: implications for cardiovascular and metabolic disease. Front Cardiovasc Med. 2022;9:1–17. The article explores the potential advantages of short-chain fatty acids (SCFAs) derived from the microbiota in the prevention and treatment of cardiovascular and metabolic diseases. Different strategies for influencing SCFAs, such as dietary adjustments, fecal microbiota transplantation, prebiotics, probiotics, and traditional Chinese medicine, show promise for upcoming therapeutic interventions.CrossRef
46.
Markowiak-Kope P, Slizewska K. The trend in the amount of SCFAs found in feces is more closely related to nutrition, environmental variables, and intestinal microbiome dysbiosis. Nutrients. 2020;12:1–23.
47.
Nakkarach A, Foo HL, Song AAL, Mutalib NEA, Nitisinprasert S, Withayagiat U. Anti-cancer and anti-inflammatory effects elicited by short chain fatty acids produced by Escherichia coli isolated from healthy human gut microbiota Microb Cell Fact. BioMed Central. 2021;20:1–17. https://​doi.​org/​10.​1186/​s12934-020-01477-z.CrossRef
48.
Angelin J, Kavitha M. Exopolysaccharides from probiotic bacteria and their health potential. Int J Biol Macromol Netherlands. 2020;162:853–65.CrossRef
49.
•• Park M, Joung M, Park JH, Ha SK, Park HY. Role of postbiotics in diet-induced metabolic disorders. Nutrients. 2022;14:1–14. The article explores the potential of postbiotics, which are substances generated or released through the metabolic activities of microorganisms, in the prevention, relief, and treatment of metabolic disorders induced by diet. Postbiotics exhibit diverse positive effects, including anti-obesity, anti-diabetic, and anti-hypertensive properties, offering potential assistance in managing metabolic disorders. Nevertheless, additional research is necessary to ascertain their effectiveness and safety.
50.
Hussain A, Zia KM, Tabasum S, Noreen A, Ali M, Iqbal R, et al. Blends and composites of exopolysaccharides; properties and applications: a review. Int J Biol Macromol Netherlands. 2017;94:10–27.CrossRef
51.
Patel S, Majumder A, Goyal A. Potentials of exopolysaccharides from lactic acid bacteria. Indian J Microbiol. 2012;52:3–12.PubMedCrossRef
52.
Kullisaar T, Zilmer M, Mikelsaar M, Vihalemm T, Annuk H, Kairane C, et al. Two antioxidative lactobacilli strains as promising probiotics. Int J Food Microbiol Netherlands. 2002;72:215–24.CrossRef
53.
Kim HS, Chae HS, Jeong SG, Ham JS, Im SK, Ahn CN, et al. In vitro antioxidative properties of lactobacilli. Asian-Australasian J Anim Sci. 2006;19:262–5.CrossRef
54.
Izuddin WI, Humam AM, Loh TC, Foo HL, Samsudin AA. Dietary postbiotic Lactobacillus plantarum improves serum and ruminal antioxidant activity and upregulates hepatic antioxidant enzymes and ruminal barrier function in post-weaning lambs. Antioxidants. 2020;9:1–13.CrossRef
55.
Chorawala MR, Chauhan S, Patel R, Shah G. Cell wall contents of probiotics (Lactobacillus species) protect against lipopolysaccharide (LPS)-induced murine colitis by limiting immuno-inflammation and oxidative stress. Probiotics Antimicrob Proteins United States. 2021;13:1005–17.CrossRef
56.
Duncker SC, Wang L, Hols P, Bienenstock J. The D-alanine content of lipoteichoic acid is crucial for Lactobacillus plantarum-mediated protection from visceral pain perception in a rat colorectal distension model. Neurogastroenterol Motil England. 2008;20:843–50.CrossRef
57.
Schauber J, Gallo RL. Antimicrobial peptides and the skin immune defense system. J Allergy Clin Immunol United States. 2008;122:261–6.CrossRef
58.
Wang Z, MacLeod DT, Di Nardo A. Commensal bacteria lipoteichoic acid increases skin mast cell antimicrobial activity against vaccinia viruses. J Immunol United States. 2012;189:1551–8.
59.
60.
61.
Morowitz MJ, Carlisle EM, Alverdy JC. Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Clin North Am. 2011;91:771–85.PubMedPubMedCentralCrossRef
62.
63.
Wang Y, Liu Y, Sidhu A, Ma Z, McClain C, Feng W. Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury. Am J Physiol Gastrointest Liver Physiol United States. 2012;303:G32–41.CrossRef
64.
Osman A, El-Gazzar N, Almanaa TN, El-Hadary A, Sitohy M. Lipolytic postbiotic from Lactobacillus paracasei manages metabolic syndrome in Albino Wistar rats. Molecules. 2021;26:1–22.CrossRef
65.
Hsu CN, Hou CY, Hsu WH, Tain YL. Cardiovascular diseases of developmental origins: preventive aspects of gut microbiota-targeted therapy. Nutrients. 2021;13:1–16.CrossRef
66.
Mosca A, Abreu Y, Abreu AT, Gwee KA, Ianiro G, Tack J, Nguyen TVH, et al. The clinical evidence for postbiotics as microbial therapeutics. Gut Microbes. 2022;14:1–14.CrossRef
67.
Peng M, Tabashsum Z, Anderson M, Truong A, Houser AK, Padilla J, et al. Effectiveness of probiotics, prebiotics, and prebiotic-like components in common functional foods. Compr Rev food Sci food Saf United States. 2020;19:1908–33.CrossRef
68.
Marques FZ, Jama HA, Tsyganov K, Gill PA, Rhys-Jones D, Muralitharan RR, et al. Guidelines for transparency on gut microbiome studies in essential and experimental hypertension  Hypertens (Dallas, Tex 1979) United States. 2019;74:1279–93.CrossRef
69.
Gill PA, van Zelm MC, Muir JG, Gibson PR. Short chain fatty acids as potential therapeutic agents in human gastrointestinal and inflammatory disorders. Aliment Pharmacol Ther. 2018;48:15–34.PubMedCrossRef
70.
Tan JK, McKenzie C, Mariño E, Macia L, Mackay CR. Metabolite-sensing G protein-coupled receptors-facilitators of diet-related immune regulation. Annu Rev Immunol United States. 2017;35:371–402.CrossRef
71.
Keshaviah PR. The role of acetate in the etiology of symptomatic hypotension. Artif Organs United States. 1982;6:378–87.CrossRef
72.
Hakim RM, Pontzer MA, Tilton D, Lazarus JM, Gottlieb MN. Effects of acetate and bicarbonate dialysate in stable chronic dialysis patients. Kidney Int United States. 1985;28:535–40.CrossRef
73.
Cen J, Sargsyan E, Bergsten P. Fatty acids stimulate insulin secretion from human pancreatic islets at fasting glucose concentrations via mitochondria-dependent and -independent mechanisms. Nutr Metab. 2016;13:1–9. 
74.
Kaye DM, Shihata WA, Jama HA, Tsyganov K, Ziemann M, Kiriazis H, et al. Deficiency of prebiotic fiber and insufficient signaling through gut metabolite-sensing receptors leads to cardiovascular disease. Circulation United States. 2020;141:1393–403.PubMedCrossRef
75.
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 United States. 2017;135:964–77.CrossRef
76.
77.
Poll BG, Xu J, Jun S, Sanchez J, Zaidman NA, He X, et al. Acetate, a short-chain fatty acid, acutely lowers heart rate and cardiac contractility along with blood pressure. J Pharmacol Exp Ther. 2021;377:39–50.PubMedPubMedCentralCrossRef
78.
Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, et al. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol Genomics United States. 2016;48:826–34.CrossRef
79.
Onyszkiewicz M, Gawrys-Kopczynska M, Konopelski P, Aleksandrowicz M, Sawicka A, Koźniewska E, et al. Butyric acid, a gut bacteria metabolite, lowers arterial blood pressure via colon-vagus nerve signaling and GPR41/43 receptors. Pflugers Arch Germany. 2019;471:1441–53.CrossRef
80.
Maeda K, Shinzato T, Nakai S, Takai I, Kobayakawa H. Mechanism of dialysis-induced hypotension. Nagoya J Med Sci. 1992;54:1–10.PubMed
81.
Suokas A, Kupari M, Heikkilä J, Lindros K, Ylikahri R. Acute cardiovascular and metabolic effects of acetate in men. Alcohol Clin Exp Res England. 1988;12:52–8.CrossRef
82.
• Jiang X, Zhang Y, Zhang H, Zhang X, Yin X, Yuan F, et al. Acetate suppresses myocardial contraction via the short-chain fatty acid receptor GPR43. Front Physiol. 2022;13:1–11. This study examines the influence of acetate, a short-chain fatty acid, on myocardial contraction in rat ventricular myocytes. The research reveals that acetate temporarily hinders contraction by interacting with the short-chain fatty acid receptor GPR43 in cardiomyocytes. Various techniques, including echocardiography, Langendorff heart perfusion, and isolated cardiomyocyte measurements, were employed to assess the effects of acetate on cardiac function and calcium handling.CrossRef
83.
Dang G, Wu W, Zhang H, Everaert N. A new paradigm for a new simple chemical: butyrate & immune regulation. Food Funct England. 2021;12:12181–93.CrossRef
84.
Stoeva MK, Garcia-So J, Justice N, Myers J, Tyagi S, Nemchek M, et al. Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease. Gut Microbes. 2021;13:1–28.PubMedCrossRef
85.
Salvi PS, Cowles RA. Butyrate and the intestinal epithelium: modulation of proliferation and inflammation in homeostasis and disease. Cells. 2021;10:1–13.CrossRef
86.
Liu H, Wang J, He T, Becker S, Zhang G, Li D, et al. Butyrate: a double-edged sword for health? Am Soc Nutr. 2018;9:21–9.
87.
Amiri P, Hosseini SA, Ghaffari S, Tutunchi H, Ghaffari S, Mosharkesh E, et al. Role of butyrate, a gut microbiota derived metabolite, in cardiovascular diseases: a comprehensive narrative review. Front Pharmacol. 2022;12:1–12.CrossRef
88.
89.
Kasahara K, Krautkramer KA, Org E, Romano KA, Kerby RL, Vivas EI, et al. Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model. Nat Microbiol England. 2018;3:1461–71.CrossRef
90.
Aguilar EC, da Silva JF, Navia-Pelaez JM, Leonel AJ, Lopes LG, Menezes-Garcia Z, et al. Sodium butyrate modulates adipocyte expansion, adipogenesis, and insulin receptor signaling by upregulation of PPAR-γ in obese Apo E knockout mice. Nutrition United States. 2018;47:75–82.
91.
Du Y, Li X, Su C, Xi M, Zhang X, Jiang Z, et al. Butyrate protects against high-fat diet-induced atherosclerosis via up-regulating ABCA1 expression in apolipoprotein E-deficiency mice. Br J Pharmacol England. 2020;177:1754–72.CrossRef
92.
Wang Y, Xu Y, Yang M, Zhang M, Xiao M, Li X. Butyrate mitigates TNF-α-induced attachment of monocytes to endothelial cells. J Bioenerg Biomembr United States. 2020;52:247–56.CrossRef
93.
Sun M, Wu W, Liu Z, Cong Y. Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. J Gastroenterol Japan. 2017;52:1–8.CrossRef
94.
Ahmed RM, Mohammed AK. Amelioration of hepatotoxicity by sodium butyrate administration in rats. World’s Vet J. 2022;12:323–9.CrossRef
95.
Ranganna K, Mathew OP, Yatsu FM, Yousefipour Z, Hayes BE, Milton SG. Involvement of glutathione/glutathione S-transferase antioxidant system in butyrate-inhibited vascular smooth muscle cell proliferation. FEBS J England. 2007;274:5962–78.CrossRef
96.
Are A, Aronsson L, Wang S, Greicius G, Yuan KL, Gustafsson JÅ, et al. Enterococcus faecalis from newborn babies regulate endogenous PPARγ activity and IL-10 levels in colonic epithelial cells. Proc Natl Acad Sci USA. 2008;105:1943–8.PubMedPubMedCentralCrossRef
97.
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 PPARγ-dependent switch from lipogenesis to fat oxidation. Diabetes United States. 2015;64:2398–408.CrossRef
98.
99.
Xiao Y, Guo Z, Li Z, Ling H, Song C. Role and mechanism of action of butyrate in atherosclerotic diseases: a review. J Appl Microbiol. 2021;131:543–52.PubMedCrossRef
100.
Li G, Yao W, Jiang H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. J Nutr United States. 2014;144:1887–95.
101.
Yan H, Ajuwon KM. Mechanism of butyrate stimulation of triglyceride storage and adipokine expression during adipogenic differentiation of porcine stromovascular cells. PLoS ONE. 2015;10:1–20.CrossRef
102.
Ciura J, Jagodziński PP. Butyrate increases the formation of anti-angiogenic vascular endothelial growth factor variants in human lung microvascular endothelial cells. Mol Biol Rep Netherlands. 2010;37:3729–34.CrossRef
103.
Cookson TA. Bacterial-induced blood pressure reduction: mechanisms for the treatment of hypertension via the gut. Front Cardiovasc Med. 2021;8:1–13.CrossRef
104.
105.
Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science United States. 2013;341:569–73.
106.
Park J-S, Lee E-J, Lee J-C, Kim W-K, Kim H-S. Anti-inflammatory effects of short chain fatty acids in IFN-gamma-stimulated RAW 264.7 murine macrophage cells: involvement of NF-kappaB and ERK signaling pathways. Int Immunopharmacol Netherlands. 2007;7:70–7.CrossRef
107.
Yang T, Magee KL, Colon-Perez LM, Larkin R, Liao Y-S, Balazic E, et al. Impaired butyrate absorption in the proximal colon, low serum butyrate and diminished central effects of butyrate on blood pressure in spontaneously hypertensive rats Acta Physiol (Oxf). Acta Physiol (Oxf) England. 2019;226:e13256.CrossRef
108.
Toral M, Robles-Vera I, de la Visitación N, Romero M, Yang T, Sánchez M, et al. Critical role of the interaction gut microbiota - sympathetic nervous system in the regulation of blood pressure. Front Physiol Switzerland. 2019;10:231.CrossRef
109.
Peng L, Li ZR, Green RS, Holzman IR, Lin J. Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. J Nutr. 2009;139:1619–25.PubMedPubMedCentralCrossRef
110.
Ermer T, Eckardt K-U, Aronson PS, Knauf F. Oxalate, inflammasome, and progression of kidney disease. Curr Opin Nephrol Hypertens England. 2016;25:363–71.CrossRef
111.
Kittanamongkolchai W, Mara KC, Mehta RA, Vaughan LE, Denic A, Knoedler JJ, et al. Risk of hypertension among first-time symptomatic kidney stone formers. Clin J Am Soc Nephrol United States. 2017;12:476–82.CrossRef
112.
Wang L, Zhu Q, Lu A, Liu X, Zhang L, Xu C, et al. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal renin-angiotensin system. J Hypertens Netherlands. 2017;35:1899–908.CrossRef
113.
Hsu C-N, Yu H-R, Lin I-C, Tiao M-M, Huang L-T, Hou C-Y, et al. Sodium butyrate modulates blood pressure and gut microbiota in maternal tryptophan-free diet-induced hypertension rat offspring. J Nutr Biochem. 2022;108:1–9.CrossRef
114.
Ichimura A, Hasegawa S, Kasubuchi M, Kimura I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol. 2014;5:1–6.CrossRef
115.
El-Azzouny M, Evans CR, Treutelaar MK, Kennedy RT, Burant CF. Increased glucose metabolism and glycerolipid formation by fatty acids and GPR40 receptor signaling underlies the fatty acid potentiation of insulin secretion*. J Biol Chem. 2014;289:13575–88.PubMedPubMedCentralCrossRef
116.
Secor JD, Fligor SC, Tsikis ST, Yu LJ, Puder M. Free fatty acid receptors as mediators and therapeutic targets in liver disease. Front Physiol. 2021;12:1–9.CrossRef
117.
•• Grundmann M, Bender E, Schamberger J, Eitner F. Pharmacology of free fatty acid receptors and their allosteric modulators. Int J Mol Sci. 2021;22:1–38. Scientists have identified numerous ligands that target allosteric sites on FFARs, aiming to create drugs for diverse diseases. Allosteric ligands for GPCRs are appealing due to their pharmacological profiles in comparison to orthosteric ligands. Despite this, the utilization of allosteric mechanisms in GPCR biology for medical purposes remains limited, with only a small number of allosteric ligands currently receiving approval. The review delves into the biology of FFARs, the molecular pharmacology of allosteric ligands targeting FFARs, and the opportunities and challenges associated with drug discovery in this context.CrossRef
118.
Schlatterer K, Peschel A, Kretschmer D. Short-chain fatty acid and FFAR2 activation – a new option for treating infections? Front Cell Infect Microbiol. 2021;11:1–9.CrossRef
119.
Mishra SP, Karunakar P, Taraphder S, Yadav H. Free fatty acid receptors 2 and 3 as microbial metabolite sensors to shape host health: pharmacophysiological view. Biomedicines. 2020;8:1–45.CrossRef
120.
Mohammad S. Role of free fatty acid receptor 2 (FFAR2) in the regulation of metabolic homeostasis. Curr Drug Targets United Arab Emirates. 2015;16:771–5.CrossRef
121.
Iván J, Major E, Sipos A, Kovács K, Horváth D, Tamás I, et al. The short-chain fatty acid propionate inhibits adipogenic differentiation of human chorion-derived mesenchymal stem cells through the free fatty acid receptor 2. Stem Cells Dev. 2017;26:1724–33.PubMedPubMedCentralCrossRef
122.
He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, et al. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism. Int J Mol Sci. 2020;21:1–16.CrossRef
123.
Nooromid M, Chen EB, Xiong L, Shapiro K, Jiang Q, Demsas F, et al. Microbe-derived butyrate and its receptor, free fatty acid receptor 3, but not free fatty acid receptor 2, mitigate neointimal hyperplasia susceptibility after arterial injury. J Am Heart Assoc. 2020;9:1–12.CrossRef
124.
Kennedy RL, Vangaveti V, Jarrod G, Baune BT. Free fatty acid receptors: emerging targets for treatment of diabetes and its complications. Ther Adv Endocrinol Metab. 2010;1:165–75.PubMedPubMedCentralCrossRef
125.
Nøhr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology United States. 2013;154:3552–64.
126.
Priyadarshini M, Layden BT. FFAR3 modulates insulin secretion and global gene expression in mouse islets. Islets United States. 2015;7:e1045182.CrossRef
127.
Zamarbide M, Martinez-Pinilla E, Gil-Bea F, Yanagisawa M, Franco R, Perez-Mediavilla A. Genetic inactivation of free fatty acid receptor 3 impedes behavioral deficits and pathological hallmarks in the APPswe Alzheimer’s disease mouse model. Int J Mol Sci. 2022;23:1–19.
128.
Jadeja RN, Jones MA, Fromal O, Powell FL, Khurana S, Singh N, et al. Loss of GPR109A/HCAR2 induces aging-associated hepatic steatosis. Aging (Albany NY). 2019;11:386–400.
129.
130.
Abdelrahman AA, Powell FL, Jadeja RN, Jones MA, Thounaojam MC, Bartoli M, et al. Expression and activation of the ketone body receptor HCAR2/GPR109A promotes preservation of retinal endothelial cell barrier function  Exp Eye Res England. 2022;221.CrossRef
131.
Yu J, Xiang JY, Xiang H, Xie Q. Cecal butyrate (not propionate) was connected with metabolism-related chemicals of mice, based on the different effects of the two Inonotus obliquus extracts on obesity and their mechanisms. ACS Omega. 2020;5:16690–700.PubMedPubMedCentralCrossRef
132.
Lin HV, Frassetto A, Kowalik EJJ, Nawrocki AR, Lu MM, Kosinski JR, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7:1–9.
133.
Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3–36): secretory controls and physiological roles in eating and glycemia in health, obesity, and after RYGB. Physiol Rev United States. 2017;97:411–63.
134.
Eslick S, Williams EJ, Berthon BS, Wright T, Karihaloo C, Gately M, et al. Weight loss and short-chain fatty acids reduce systemic inflammation in monocytes and adipose tissue macrophages from obese subjects. Nutrients. 2022;14:1–17.
135.
•• van Deuren T, Blaak EE, Canfora EE. Butyrate to combat obesity and obesity-associated metabolic disorders: current status and future implications for therapeutic use. Obes Rev. 2022;23:1–27. Butyrate, a short-chain fatty acid synthesized by gut bacteria, exhibits potential therapeutic benefits for obesity and associated metabolic disorders. Findings from animal studies indicate favorable effects on adipose tissue metabolism, inflammation, insulin sensitivity, and the regulation of body weight. Nevertheless, human research is restricted, and variations among individuals suggest that results might be influenced by personal characteristics. Subsequent research should explore factors affecting treatment outcomes and refine targeted interventions for optimization.
136.
Mayorga-Ramos A, Barba-Ostria C, Simancas-Racines D, Guamán LP. Protective role of butyrate in obesity and diabetes: New insights. Front Nutr. 2022;9:1–9.CrossRef
137.
Zhu W, Peng K, Zhao Y, Xu C, Tao X, Liu Y, et al. Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation. Front Pharmacol. 2022;13:1–13.
138.
Kushwaha V, Rai P, Varshney S, Gupta S, Khandelwal N, Kumar D, et al. Sodium butyrate reduces endoplasmic reticulum stress by modulating CHOP and empowers favorable anti-inflammatory adipose tissue immune-metabolism in HFD fed mice model of obesity. Food Chem Mol Sci. 2022;4:1–11.
139.
Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: a comparative study with metformin. Chem Biol Interact Ireland. 2016;254:124–34.CrossRef
140.
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 β(3)-adrenergic receptor activation in high-fat diet-induced obese mice. Exp Physiol England. 2017;102:273–81.CrossRef
141.
Jia X, Xu W, Zhang L, Li X, Wang R, Wu S. Impact of gut microbiota and microbiota-related metabolites on hyperlipidemia. Front Cell Infect Microbiol. 2021;11:1–14.CrossRef
142.
Oyabambi AO, Olaniyi KS. Sodium butyrate aggravates glucose dysregulation and dyslipidemia in high fat-fed Wistar rats  Metab Open England. 2023;17:100226.CrossRef
143.
Hong J, Jia Y, Pan S, Jia L, Li H, Han Z, et al. Butyrate alleviates high fat diet-induced obesity through activation of adiponectin-mediated pathway and stimulation of mitochondrial function in the skeletal muscle of mice. Oncotarget United States. 2016;7:56071–82.CrossRef
144.
Karoor V, Strassheim D, Sullivan T, Verin A, Umapathy NS, Dempsey EC, et al. The short-chain fatty acid butyrate attenuates pulmonary vascular remodeling and inflammation in hypoxia-induced pulmonary hypertension. Int J Mol Sci. 2021;22:1–19.CrossRef
145.
Panagia M, He H, Baka T, Pimentel DR, Croteau D, Bachschmid MM, et al. Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease. NMR Biomed. 2020;33:1–10.CrossRef
146.
Kirschner SK, Deutz NEP, Rijnaarts I, Smit TJ, Larsen DJ, Engelen MPKJ. Impaired intestinal function is associated with lower muscle and cognitive health and well-being in patients with congestive heart failure. JPEN J Parenter Enteral Nutr United States. 2022;46:660–70.CrossRef
147.
Tilves C, Yeh HC, Maruthur N, Juraschek SP, Miller E, White K, et al. Increases in circulating and fecal butyrate are associated with reduced blood pressure and hypertension: results from the SPIRIT trial. J Am Heart Assoc. 2022;11:1–9.
148.
Dardi P, dos Santos-Eichler RA, de Oliveira S, Vinolo MAR, Câmara NOS, Rossoni LV. Reduced intestinal butyrate availability is associated with the vascular remodeling in resistance arteries of hypertensive rats. Front Physiol. 2022;13:1–12.CrossRef
149.
Zhang L, Deng M, Lu A, Chen Y, Chen Y, Wu C, et al. Sodium butyrate attenuates angiotensin II-induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6-dependent mechanism. J Cell Mol Med. 2019;23:8139–50.PubMedPubMedCentralCrossRef
150.
Robles-Vera I, Toral M, de la Visitación N, Sánchez M, Gómez-Guzmán M, Romero M, et al. Probiotics prevent dysbiosis and the rise in blood pressure in genetic hypertension: role of short-chain fatty acids  Mol Nutr Food Res Germany. 2020;64:e1900616.CrossRef
151.
Wang Y, Xu Y, Yang M, Zhang M, Xiao M, Li X. Butyrate mitigates TNF-α-induced attachment of monocytes to endothelial cells. J Bioenerg Biomembr Journal of Bioenergetics and Biomembranes. 2020;52:247–56.PubMedCrossRef
152.
Marcil V, Delvin E, Seidman E, Poitras L, Zoltowska M, Garofalo C, et al. Modulation of lipid synthesis, apolipoprotein biogenesis, and lipoprotein assembly by butyrate. Am J Physiol - Gastrointest Liver Physiol. 2002;283:340–6.CrossRef
153.
Barcelos RCS, de Mello-Sampayo C, Antoniazzi CTD, Segat HJ, Silva H, Veit JC, et al. Oral supplementation with fish oil reduces dryness and pruritus in the acetone-induced dry skin rat model. J Dermatol Sci Netherlands. 2015;79:298–304.CrossRef
154.
155.
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 United States. 2019;139:1407–21.CrossRef
156.
Osto E. The promise of the gut metabolite propionate for a novel and personalized lipid-lowering treatment. Eur Heart J. 2022;43:534–7.PubMedCrossRef
157.
Pakhomov N, Baugh JA. The role of diet-derived short-chain fatty acids in regulating cardiac pressure overload. Am J Physiol - Hear Circ Physiol. 2021;320:H475–86.CrossRef
158.
Ward NC, Carnagarin R, Nolde JM, Lugo-Gavidia LM, Chan J, Jose A, et al. Circulating short-chain fatty acids in hypertension: a reflection of various hypertensive phenotypes. J Hypertens Netherlands. 2022;40:1589–96.CrossRef
159.
Tain Y, Hou C, Lin S, Tzeng H, Lee W, Wu KLH, et al. Reprogramming effects of postbiotic butyrate and propionate on maternal high fructose diet-induced offspring hypertension. Nurtients. 2023;15:1–15.
160.
Kassan M, Kwon Y, Munkhsaikhan U, Sahyoun AM, Ishrat T, Galán M, et al. Protective role of short-chain fatty acids against Ang-II-induced mitochondrial dysfunction in brain endothelial cells: a potential role of heme oxygenase 2. Antioxidants. 2023;12:1–14.CrossRef
161.
Cismaru CA, Cismaru GL, Burz C, Nutu A, IBN. SARS-CoV-2 – the hidden agonist of the pressor arm of renin- angiotensin system : considerations for statins and propionate derivatives. J Med Radiat Oncol. 2021;1:131–8.
162.
Chinnathambi V, Blesson CS, Vincent KL, Saade GR, Hankins GD, Yallampalli C, et al. Elevated testosterone levels during rat pregnancy cause hypersensitivity to angiotensin II and attenuation of endothelium-dependent vasodilation in uterine arteries. Hypertens (Dallas, Tex 1979) United States; 2014;64:405–14.
163.
Muralitharan RR, Marques FZ. Diet-related gut microbial metabolites and sensing in hypertension. J Hum Hypertens. 2021;35:162–9.CrossRef
164.
• Haghikia A, Zimmermann F, Schumann P, Jasina A, Roessler J, Schmidt D, et al. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism. Eur Heart J. 2022;43:518–33. The research investigates how propionic acid (PA), a byproduct originating from the gut microbiota, influences the metabolism of cholesterol in the intestines and the development of atherosclerosis. Furthermore, it assesses how PA affects the levels of factors related to glucose metabolism and lipid regulation in the plasma. The findings reveal that PA diminishes atherosclerosis through immune-dependent control of intestinal cholesterol metabolism, leading to a reduction in cholesteryl esters. Moreover, a clinical trial illustrates the impact of PA on LDL and overall cholesterol levels in individuals dealing with hypercholesterolemia.PubMedCrossRef
165.
Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol England. 2017;19:29–41.CrossRef
166.
Yi C, Sun W, Ding L, Yan M, Sun C, Qiu C, et al. Short-chain fatty acids weaken ox-LDL-induced cell inflammatory injury by inhibiting the NLRP3/caspase-1 pathway and affecting cellular metabolism in THP-1 cells. Molecules. 2022;27:1–15.CrossRef
167.
Hou Y-F, Shan C, Zhuang S-Y, Zhuang Q-Q, Ghosh A, Zhu K-C, et al. Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson’s disease  Microbiome England. 2021;9:34.CrossRef
168.
169.
Ang Z, Ding JL. GPR41 and GPR43 in obesity and inflammation - protective or causative? Front Immunol. 2016;7:1–5.CrossRef
170.
Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki S-I, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol an Off J Polish Physiol Soc Poland. 2008;59(Suppl 2):251–62.
171.
Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun. 2013;4:1–12.
172.
Bellahcene M, O’Dowd JF, Wargent ET, Zaibi MS, Hislop DC, Ngala RA, et al. Male mice that lack the G-protein-coupled receptor GPR41 have low energy expenditure and increased body fat content. Br J Nutr. 2013;109:1755–64.PubMedCrossRef
173.
Carbone AM, Borges JI, Suster MS, Sizova A, Cora N, Desimine VL, et al. Regulator of G-protein signaling-4 attenuates cardiac adverse remodeling and neuronal norepinephrine release-promoting free fatty acid receptor FFAR3 signaling. Int J Mol Sci. 2022;23:1–13.
174.
175.
Park BO, Kim SH, Kim JH, Kim SY, Park BC, Han SB, et al. The short-chain fatty acid receptor gpr43 modulates yap/taz via rhoa. Mol Cells. 2021;44:458–67.PubMedPubMedCentralCrossRef
176.
Nakajima A, Nakatani A, Hasegawa S, Irie J, Ozawa K, Tsujimoto G, et al. The short chain fatty acid receptor GPR43 regulates inflammatory signals in adipose tissue M2-type macrophages. PLoS ONE. 2017;12:1–18.CrossRef
177.
Bros M, Haas K, Moll L, Grabbe S. RhoA as a key regulator of innate and adaptive immunity. Cells. 2019;8:1–30.
178.
Mosaddad SA, Salari Y, Amookhteh S, Soufdoost RS, Seifalian A, Bonakdar S, et al. Response to mechanical cues by interplay of YAP/TAZ transcription factors and key mechanical checkpoints of the cell: a comprehensive review. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol Germany. 2021;55:33–60.CrossRef
179.
Yoo H, Singh A, Li H, Strat AN, Bagué T, Ganapathy PS, et al. Simvastatin attenuates glucocorticoid-induced human trabecular meshwork cell dysfunction via YAP/TAZ inactivation. Curr Eye Res England. 2023;48:736–49.CrossRef
180.
Kobayashi M, Mikami D, Kimura H, Kamiyama K, Morikawa Y, Yokoi S, et al. Short-chain fatty acids, GPR41 and GPR43 ligands, inhibit TNF-α-induced MCP-1 expression by modulating p38 and JNK signaling pathways in human renal cortical epithelial cells. Biochem Biophys Res Commun United States. 2017;486:499–505.CrossRef
181.
Luo QJ, Sun MX, Guo YW, Tan SW, Wu XY, Abassa KK, et al. Sodium butyrate protects against lipopolysaccharide-induced liver injury partially via the GPR43/β-arrestin-2/NF-κB network. Gastroenterol Rep. 2021;9:154–65.CrossRef
182.
Chen L, Yuan J, Li H, Ding Y, Yang X, Yuan Z, et al. Trans-cinnamaldehyde attenuates renal ischemia/reperfusion injury through suppressing inflammation via JNK/p38 MAPK signaling pathway. Int Immunopharmacol Netherlands. 2023;118:110088.CrossRef
183.
Metadata
Title
Management of Cardiovascular Diseases by Short-Chain Fatty Acid Postbiotics
Authors
Seyed Sadeq Mousavi Ghahfarrokhi
Mohamadsadegh Mohamadzadeh
Nasrin Samadi
Mohammad Reza Fazeli
Sara Khaki
Bahman Khameneh
Ramin Khameneh Bagheri
Publication date
24-04-2024
Publisher
Springer US
Published in
Current Nutrition Reports
Electronic ISSN: 2161-3311
DOI
https://doi.org/10.1007/s13668-024-00531-1

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