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Fusco, W.; Lorenzo, M.B.; Cintoni, M.; Porcari, S.; Rinninella, E.; Kaitsas, F.; Lener, E.; Mele, M.C.; Gasbarrini, A.; Collado, M.C.; et al. Role of Short-Chain Fatty Acids in Human Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/44046 (accessed on 22 April 2024).
Fusco W, Lorenzo MB, Cintoni M, Porcari S, Rinninella E, Kaitsas F, et al. Role of Short-Chain Fatty Acids in Human Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/44046. Accessed April 22, 2024.
Fusco, William, Manuel Bernabeu Lorenzo, Marco Cintoni, Serena Porcari, Emanuele Rinninella, Francesco Kaitsas, Elena Lener, Maria Cristina Mele, Antonio Gasbarrini, Maria Carmen Collado, et al. "Role of Short-Chain Fatty Acids in Human Diseases" Encyclopedia, https://encyclopedia.pub/entry/44046 (accessed April 22, 2024).
Fusco, W., Lorenzo, M.B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M.C., Gasbarrini, A., Collado, M.C., Cammarota, G., & Ianiro, G. (2023, May 09). Role of Short-Chain Fatty Acids in Human Diseases. In Encyclopedia. https://encyclopedia.pub/entry/44046
Fusco, William, et al. "Role of Short-Chain Fatty Acids in Human Diseases." Encyclopedia. Web. 09 May, 2023.
Role of Short-Chain Fatty Acids in Human Diseases
Edit

Short-chain fatty acids (SCFAs) are organic acids whose carbon chain is composed of less than six carbons. Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs play a significant anti-inflammatory role in the regulation of immune function, taking part in the prevention of various inflammatory chronic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa.

short-chain fatty acids butyrate gut microbiota SCFA-producing bacteria gut health prebiotics probiotics diet

1. Introduction

Short-chain fatty acids (SCFAs) are organic acids whose carbon chain is composed of less than six carbons. Among these, acetate (C2), propionate (C3) and butyrate (C4) are the most represented [1]. Acetate contributes to approximately 60% of the total SCFAs while propionate and butyrate comprise 20% each [2]. Additional acids, including lactate isomers, valerate, and branched chain SCFAs such as isobutyrate and iso-valerate, can be found in our gut metabolome (the metabolites of our gut microbiome), but their levels are noticeably lower compared with the main acids [3].
The main functions of SCFAs are carried out with the aid of Free Fatty Acid Receptor 2 (FFAR2) and FFAR3, while FFAR1 and FFAR4 are used by medium- and long-chain fatty acids. FFARs are G-protein-coupled transmembrane receptors located on the surface of many different cells (neurons, colonocytes, pancreatic cells, neutrophils, adipocytes, enteroendocrine cells, etc.) [4]. Acetate, a C2 SCFA, is more effective in the activation of the FFAR2 receptor, while propionate, a C3 SCFA, mainly effects the FFAR3 receptor. These receptors play key roles in various cells. FFAR2 and FFAR3 could mediate both the anti-inflammatory effect of acetate and propionate, and the proinflammatory effect of butyrate on innate immune system cells [5]. Moreover, the action of those two receptors may influence the energy consumption of neurons [6], insulin secretion from Langerhans islets beta cells [7][8] and enteroendocrine function [9][10].
The effects of SCFAs on the human gut are mediated by the presence of SCFA transporters on colonic epithelium. These transporters can be grouped into three main transporter classes: proton-coupled transporters, such as MCT1 and MCT4; sodium-coupled transporters, using the energy of two sodium ions, such as SMCT1; and ATP-dependent transporters, such as ABCG2, also known as breast cancer resistance protein (BCRP) [11].
SCFAs have several beneficial effects on human health, at different levels and on body sites.
First, SCFAs promote the integrity and permeability of the gut barrier in different ways. These molecules, mainly butyrate, increase the concentration of tight junctions, such as claudin-1, zonula occludens-1 and occludin through the upregulation of genes that encode for these proteins [12]. Moreover, butyrate is able to strengthen the mucus layer of the gut epithelium by increasing the expression of Mucin 2 [13]. Butyrate is also involved in the modulation of oxidative stress, as it reduces H2O2-induced DNA damage, restoring the levels of antioxidant glutathione. Additionally, SCFAs can induce both the differentiation and apoptosis of colonic cells, ideally preventing the development of colon cancer, as discussed further in this research [14].
SCFAs also play an important role in the regulation of several physiological pathways within the nervous system. First, SCFAs modulate brain-induced intestinal gluconeogenesis. In particular, when propionate is absorbed and passes through the portal vein, it activates the FFAR3s present on the surface of afferent periportal neurons [15]. SCFAs also regulate the inhibition of histone deacetylase (HDAC), with a potential impact on several neuropsychiatric diseases such as depression, schizophrenia and Alzheimer’s disease [16]. Moreover, SCFAs control systemic and neuroinflammation through the modulation of functions and structures of microglia cells, resulting in the modulation of emotion, cognition and mental disorders. Additionally, high concentrations of SCFAs seem to be related to the major expression of neurotrophic factors [17]; SCFAs may induce the expression of tryptophan 5-hydroxylase 1, an enzyme involved in serotonin biosynthesis [18], and there is also evidence that they may positively affect the brain barrier’s integrity [19][20].
SCFAs, especially acetate, are also involved in the regulation of appetite and human metabolism. In animal models, diets with a high abundance of fermentable carbohydrates, whose catabolism in the colon generates SCFAs, relate to a minor appetite [21]. Moreover, acetate may reduce body weight through the secretion of glucagon-like peptide 1 and peptide YY [22]. SCFAs are also able to modulate both glucose and lipid metabolism. Propionate suppresses hepatic gluconeogenesis [23], while both acetate and butyrate reduce lipogenesis and increase leptin secretion [24][25][26][27]. Furthermore, SCFA administration in animal models seems to reduce liver steatosis [28][29], and vinegar, a food rich in acetate, was demonstrated to be useful in reducing body weight, serum triglycerides and body fat mass [30]. However, most experiences on humans are biased by a small sample size, and more evidence from adequately sized clinical studies is needed to understand the effects of SCFAs on lipidic metabolism [31].
Increasing evidence suggests that SCFAs are able to influence other components of cardiometabolic health. Increased levels of butyrate and propionate are associated with the reduction in blood pressure [32] and plasminogen activator inhibitor-1 (PAI-1) levels, a pro-thrombotic factor [33].
Notably, SCFAs have a relevant impact on both innate and adaptive immunity. Regarding innate immunity, SCFAs can act directly on neutrophils, reducing their production of reactive oxygen species (ROS) and myeloperoxidase (MPO), and can even enhance their apoptosis [34]. They also reduce the chemotaxis of inflammatory cells due to a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM1) and chemokines signals [35][36]. In addition, regarding the T cell lineage, SCFAs can increase the Treg cell number and their activity and inhibit CD4+ [37][38]. Finally, treatment with SCFAs, and especially with butyrate, is able to reduce gut inflammation, reducing the NF-κB signaling pathway and enhancing the expression of anti-inflammatory cytokines such as IL-10 [39].
In gut diseases, both acute and chronic inflammation are relevant. Transient acute inflammation, an essential defense mechanism of the immune system against injurious stimuli, is of particular relevant [40][41]. In this condition, when cells are damaged, instead of directly targeting the injurious stimuli, such as any invading viruses or bacteria, the immune system will use the “self-destroy and rebuild” strategy, targeting the damaged cells. By using a programmed cell death such as pyroptosis [42] and necroptosis [43] to actively destroy the cells, stimuli such as viruses or bacteria are also effectively cleared. On the other hand, chronic inflammation develops when the stimulus cannot be removed and is associated with diseases like IBDs, where SCFAs play a key role [44].

2. SCFAs and IBD

IBD includes chronic inflammatory disorders of the gastrointestinal tract associated with a gut microbiota imbalance. Patients with IBD are known to share, compared with healthy subjects, a reduction in butyrate producers of the Firmicutes phylum, mainly Roseburia spp and Faecalibacterium prausnitzii, and an increase in opportunistic bacteria [45][46].
In addition to a reduced SCFAs production, the uptake and oxidation of butyrate appears to be inhibited in patients with UC [47]. This leads to a weakening of their anti-inflammatory activity, thus promoting disease progression. More specifically, propionate and butyrate stimulate T-reg proliferation and function through GPR-43 pathways and HDACs’ inhibition [48][49][50]. SCFAs also lead to a downregulation of proinflammatory cytokines levels because of the inhibition of NF-κB and HDCAs activity [51][52][53], and to an increase in the anti-inflammatory ones through GPCRs [36].
Furthermore, acetate controls tissue homeostasis through NLRP-3 activation [54] and butyrate regulates the intestinal barrier, which is known to be impaired in IBD, through increased AREG, IL-22 and claudin-1 production [55][56].

3. SCFAs and Colorectal Cancer (CRC)

CRC is a multifactorial disease and the gut microbiota play an important role in its development [57]. Patients with CRC showed an increase in pathogenic bacteria (e.g., Fusobacterium nucleatum) and a depletion in butyrate producers [52][58][59]. The reduced production of SCFAs leads to a pro-inflammatory environment, which can contribute to the initiation and progression of CRC [60]. In addition, butyrate can change redox state and D-glucose metabolism, enhancing cancer cells’ apoptosis [61], while the inhibition of HDCAs regulates the expression of p21, arresting cell cycle and consequent cancer proliferation [62]. Proliferation is also inhibited by propionate via GPR-43, which is often lost in colon cancer cells [63].

4. SCFAs and Cardiovascular Diseases (CVDs)

There is a large body of evidence suggesting that SCFAs play a role in the pathogenesis of CVDs, a group of disorders that include hypertension and atherosclerosis. A reduction in butyrate producers in the gut microbiota and the deficient intestinal absorption of SCFAs have been observed in patients with hypertension [64][65]. Moreover, SCFAs appear to have a dual effect on the regulation of blood pressure. For example, when binding Olfr-78, acetate and propionate lead to renin release, increasing blood pressure [66]. By contrast, when binding GPR-41, they reduce blood pressure via vasodilatation [67], which is also obtained by the effect of butyrate on afferent vagal terminals [68]. In atherosclerosis, a similar pathway has been noted [69], as SCFAs, mainly butyrate, appear to play a protective role in the regulation of inflammation and stabilization of plaques by downregulating the expression of CCL-2, VCAM-1, and MMP-2, resulting in the lower migration of macrophages, increased collagen deposition and ultimate plaque stability [70].

5. SCFAs and Metabolic Diseases

As anticipated above, SCFAs regulate metabolic pathways and food intake, thereby playing a role in the development of metabolic diseases. Obesity is associated with an imbalance in the gut microbiota, mainly an increased Firmicutes/Bacteroidetes ratio, and an increase in fecal-SCFAs [71][72], although circulating SCFAs are reduced [73]. Type 2 diabetes (T2D) is instead characterized by a decrease in butyrate producers in the gut microbiota [74].
Normally, SCFAs moderate food intake, stimulating the secretion of satiety hormones such as PYY and GLP-1 via GPR-41 and GPR-43 [75][76] and through the inhibition of HDACs [77]. Furthermore, acetate can cross the blood–brain barrier, causing a decreasee in appetite [21]. SCFAs can also improve glucose homeostasis in an AMPK-dependent manner involving PPARγ-regulated effects on gluconeogenesis and lipogenesis [24]. Moreover, propionate enhances glucose-stimulated insulin release via GPR-43 and increases β-cell mass [78]. SCFAs can stimulate adipocyte differentiation [79][80] and decrease lipid plasma levels through the inhibition of lipolysis and stimulation of lipogenesis [81][82][83] and cholesterol plasma levels, enhancing its hepatic uptake [84].
Overall, these mechanistic pathways of SCFAs in different disorders pave the way for the therapeutic use of SCFAs in clinical practice. Table 1.
Table 1. The role of short-chain fatty acids in different disorders.
Disease SCFA Model Function Ref.
Inflammatory bowel disease Acetate Gpr43−/−, Gpr109a−/−, Nlrp3−/− and Nlrp6−/− mice Induces NLRP3 inflammosome activation to maintain tissue homeostasis [47]
  Butyrate Niacr1+/− Apc min/+ and Niacr1−/− Apc min/+ mice Increases colonic DCs and macrophages’ production of IL-10, inducing Treg generation [40]
    Foxp3 ΔCNS1, Foxp3 GFP, Foxp3 Thy1.1 and Gpr109a−/− mice Promotes Treg differentiation through enhancing Foxp3 activity [41]
    GPR109a−/− and WT mice Inhibits AKT and NF-κB p65 signaling pathways in macrophages [44]
    BMDM cells,
C57BL/6 and CX3CR1-GFP/+ mice
Reduces NO, IL-6 and IL-12p40 secretion by macrophages [46]
    GPR43−/−, Prdm1−/− and WT mice Increases AREG expression levels in DCs to promote tissue repair [48]
    Cdx2-IEC monolayer Induces production of claudin-1 to enhance barrier functions [52]
  Propionate Gpr43−/− and Gpr43+/+ mice Promotes Treg differentiation through GPR-43 [42]
  All SCFAs HeLa and HEK293 cell lines Inhibit NF-κB activity through GPR43—βarrestin interactions [43]
    Isolated human neutrophils, monocytes and PBMC Promotes anti-inflammatory effects via the regulation of PGE2, cytokine and chemokine release [34]
    CD4+ T cells and ILCs Induces production of IL-22 to promote barrier functions [49]
Colorectal cancer Butyrate Caco-2 cell line Enhances cancer cells’ apoptosis by alterations in the redox state and D-glucose metabolism [54]
    MCF-7 (T5) and MDA MB 231 cell lines Arrests cancer cells’ proliferation through upregulation of p21 [55]
  Propionate Caco-2, HCT116, HCT8, HT-29, SW620, SW480, CBS, FET and MOSER cell lines Arrests cancer cells’ proliferation through p21 upregulation and decrease in cyclin D3, CDK-1 and CDK-2 [56]
Hypertension Acetate and propionate Olfr78−/− and Gpr41−/− mice Increase blood pressure through Olfr-78 [58]
    Gpr41−/− and WT mice Reduces blood pressure by binding GRP-41 [59]
  Butyrate Vagotomized Sheffield strain male Wistar rats Reduces blood pressure through the regulation of afferent vagal terminals [60]
Atherosclerosis Butyrate ApoE −/− mice Reduces CCL-2, VCAM-1, and MMP-2 production to stabilize atherosclerotic plaques [62]
Obesity Acetate C57BL/6 male mice Decreases appetite through central hypothalamic mechanisms [19]
  Propionate Isolated human colonic cells Reduces food intake through the secretion of PPY and GLP-1 via GPR-41 [68]
  Propionate and butyrate NCI-h716 and HuTu-80 cells Reduce food intake through the secretion of PPY via inhibition of HDACs [69]
Metabolic syndrome Acetate Isolated adipocytes from GPR43 knockout mice Decreases lipid plasma levels through inhibition of lipolysis via GPR-43 [75]
  Propionate Human subjects and in vitro isolated human islets Enhances glucose-stimulated insulin release and increases β-cell mass [70]
    Human adipose tissue culture Decreases lipid plasma levels by stimulating lipogenesis [76]
  Propionate and butyrate Stromal vascular fraction of the porcine subcutaneous fat Stimulates adipocyte differentiation [72]
  All SCFAs PPARγ f/f and PPARγ lox/lox mice Regulate gluconeogenesis and lipogenesis through PPARγ downregulation [22]
    Male Golden hamsters Decrease cholesterol plasma levels by enhancing its hepatic uptake [77]

References

  1. Mortensen, P.B.; Clausen, M.R. Short-chain fatty acids in the human colon: Relation to gastrointestinal health and disease. Scand. J. Gastroenterol. Suppl. 1996, 216, 132–148.
  2. Topping, D.L.; Clifton, P.M. Short-chain fatty acids and human colonic function: Roles of resistant starch and nonstarch polysaccharides. Physiol. Rev. 2001, 81, 1031–1064.
  3. Topping, D.L. Short-chain fatty acids produced by intestinal bacteria. Asia Pac. J. Clin. Nutr. 1996, 5, 15–19.
  4. Kimura, I.; Ichimura, A.; Ohue-Kitano, R.; Igarashi, M. Free Fatty Acid Receptors in Health and Disease. Physiol. Rev. 2020, 100, 171–210.
  5. Bolognini, D.; Tobin, A.B.; Milligan, G.; Moss, C.E. The Pharmacology and Function of Receptors for Short-Chain Fatty Acids. Mol. Pharmacol. 2016, 89, 388–398.
  6. Kimura, I.; Inoue, D.; Maeda, T.; Hara, T.; Ichimura, A.; Miyauchi, S.; Kobayashi, M.; Hirasawa, A.; Tsujimoto, G. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc. Natl. Acad. Sci. USA 2011, 108, 8030–8035.
  7. Priyadarshini, M.; Layden, B.T. FFAR3 modulates insulin secretion and global gene expression in mouse islets. Islets 2015, 7, e1045182.
  8. Priyadarshini, M.; Villa, S.R.; Fuller, M.; Wicksteed, B.; Mackay, C.R.; Alquier, T.; Poitout, V.; Mancebo, H.; Mirmira, R.G.; Gilchrist, A.; et al. An Acetate-Specific GPCR, FFAR2, Regulates Insulin Secretion. Mol. Endocrinol. Baltim. Md. 2015, 29, 1055–1066.
  9. Tolhurst, G.; Heffron, H.; Lam, Y.S.; Parker, H.E.; Habib, A.M.; Diakogiannaki, E.; Cameron, J.; Grosse, J.; Reimann, F.; Gribble, F.M. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes 2012, 61, 364–371.
  10. Akiba, Y.; Inoue, T.; Kaji, I.; Higashiyama, M.; Narimatsu, K.; Iwamoto, K.; Watanabe, M.; Guth, P.H.; Engel, E.; Kuwahara, A.; et al. Short-chain Fatty Acid Sensing in Rat Duodenum. J. Physiol. 2015, 593, 585–599.
  11. Sivaprakasam, S.; Bhutia, Y.D.; Yang, S.; Ganapathy, V. Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis. Compr. Physiol. 2017, 8, 299–314.
  12. Chen, G.; Ran, X.; Li, B.; Li, Y.; He, D.; Huang, B.; Fu, S.; Liu, J.; Wang, W. Sodium Butyrate Inhibits Inflammation and Maintains Epithelium Barrier Integrity in a TNBS-induced Inflammatory Bowel Disease Mice Model. EBioMedicine 2018, 30, 317–325.
  13. Liang, L.; Liu, L.; Zhou, W.; Yang, C.; Mai, G.; Li, H.; Chen, Y. Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/WNT/ERK signaling pathway. Clin. Sci. 2022, 136, 291–307.
  14. Liu, P.; Wang, Y.; Yang, G.; Zhang, Q.; Meng, L.; Xin, Y.; Jiang, X. The role of short-chain fatty acids in intestinal barrier function, inflammation, oxidative stress, and colonic carcinogenesis. Pharmacol. Res. 2021, 165, 105420.
  15. De Vadder, F.; Kovatcheva-Datchary, P.; Goncalves, D.; Vinera, J.; Zitoun, C.; Duchampt, A.; Bäckhed, F.; Mithieux, G. Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits. Cell 2014, 156, 84–96.
  16. Mirzaei, R.; Bouzari, B.; Hosseini-Fard, S.R.; Mazaheri, M.; Ahmadyousefi, Y.; Abdi, M.; Jalalifar, S.; Karimitabar, Z.; Teimoori, A.; Keyvani, H.; et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders. Biomed. Pharmacother. Biomed. Pharmacother. 2021, 139, 111661.
  17. Yang, L.L.; Millischer, V.; Rodin, S.; MacFabe, D.F.; Villaescusa, J.C.; Lavebratt, C. Enteric short-chain fatty acids promote proliferation of human neural progenitor cells. J. Neurochem. 2020, 154, 635–646.
  18. Nankova, B.B.; Agarwal, R.; MacFabe, D.F.; La Gamma, E.F. Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission, in PC12 cells—Possible relevance to autism spectrum disorders. PLoS ONE 2014, 9, e103740.
  19. Hoyles, L.; Snelling, T.; Umlai, U.-K.; Nicholson, J.K.; Carding, S.R.; Glen, R.C.; McArthur, S. Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier. Microbiome 2018, 6, 55.
  20. Dalile, B.; Van Oudenhove, L.; Vervliet, B.; Verbeke, K. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 461–478.
  21. Frost, G.; Sleeth, M.L.; Sahuri-Arisoylu, M.; Lizarbe, B.; Cerdan, S.; Brody, L.; Anastasovska, J.; Ghourab, S.; Hankir, M.; Zhang, S.; et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 2014, 5, 3611.
  22. González Hernández, M.A.; Canfora, E.E.; Jocken, J.W.E.; Blaak, E.E. The Short-Chain Fatty Acid Acetate in Body Weight Control and Insulin Sensitivity. Nutrients 2019, 11, 1943.
  23. Yoshida, H.; Ishii, M.; Akagawa, M. Propionate suppresses hepatic gluconeogenesis via GPR43/AMPK signaling pathway. Arch. Biochem. Biophys. 2019, 672, 108057.
  24. den Besten, G.; Bleeker, A.; Gerding, A.; van Eunen, K.; Havinga, R.; van Dijk, T.H.; Oosterveer, M.H.; Jonker, J.W.; Groen, A.K.; Reijngoud, D.-J.; et al. Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPARγ-Dependent Switch From Lipogenesis to Fat Oxidation. Diabetes 2015, 64, 2398–2408.
  25. Weitkunat, K.; Schumann, S.; Nickel, D.; Kappo, K.A.; Petzke, K.J.; Kipp, A.P.; Blaut, M.; Klaus, S. Importance of propionate for the repression of hepatic lipogenesis and improvement of insulin sensitivity in high-fat diet-induced obesity. Mol. Nutr. Food Res. 2016, 60, 2611–2621.
  26. Xiong, Y.; Miyamoto, N.; Shibata, K.; Valasek, M.A.; Motoike, T.; Kedzierski, R.M.; Yanagisawa, M. Short-chain fatty acids stimulate leptin production in adipocytes through the G protein-coupled receptor GPR41. Proc. Natl. Acad. Sci. USA 2004, 101, 1045–1050.
  27. Soliman, M.M.; Ahmed, M.M.; Salah-Eldin, A.-E.; Abdel-Aal, A.A.-A. Butyrate regulates leptin expression through different signaling pathways in adipocytes. J. Vet. Sci. 2011, 12, 319–323.
  28. Deng, M.; Qu, F.; Chen, L.; Liu, C.; Zhang, M.; Ren, F.; Guo, H.; Zhang, H.; Ge, S.; Wu, C.; et al. SCFAs alleviated steatosis and inflammation in mice with NASH induced by MCD. J. Endocrinol. 2020, 245, 425–437.
  29. Shimizu, H.; Masujima, Y.; Ushiroda, C.; Mizushima, R.; Taira, S.; Ohue-Kitano, R.; Kimura, I. Dietary short-chain fatty acid intake improves the hepatic metabolic condition via FFAR3. Sci. Rep. 2019, 9, 16574.
  30. Kondo, T.; Kishi, M.; Fushimi, T.; Ugajin, S.; Kaga, T. Vinegar intake reduces body weight, body fat mass, and serum triglyceride levels in obese Japanese subjects. Biosci. Biotechnol. Biochem. 2009, 73, 1837–1843.
  31. Morrison, D.J.; Preston, T. Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes 2016, 7, 189–200.
  32. Hu, T.; Wu, Q.; Yao, Q.; Jiang, K.; Yu, J.; Tang, Q. Short-chain fatty acid metabolism and multiple effects on cardiovascular diseases. Ageing Res. Rev. 2022, 81, 101706.
  33. Mortensen, F.V.; Jørgensen, B.; Christiansen, H.M.; Sloth-Nielsen, J.; Wolff, B.; Hessov, I. Short-chain fatty acid enemas stimulate plasminogen activator inhibitor-1 after abdominal aortic graft surgery: A double-blinded, placebo-controlled study. Thromb. Res. 2000, 98, 361–366.
  34. Maslowski, K.M.; Vieira, A.T.; Ng, A.; Kranich, J.; Sierro, F.; Yu, D.; Schilter, H.C.; Rolph, M.S.; Mackay, F.; Artis, D.; et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 2009, 461, 1282–1286.
  35. Zapolska-Downar, D.; Naruszewicz, M. Propionate reduces the cytokine-induced VCAM-1 and ICAM-1 expression by inhibiting nuclear factor-kappa B (NF-kappaB) activation. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2009, 60, 123–131.
  36. Cox, M.A.; Jackson, J.; Stanton, M.; Rojas-Triana, A.; Bober, L.; Laverty, M.; Yang, X.; Zhu, F.; Liu, J.; Wang, S.; et al. Short-chain fatty acids act as antiinflammatory mediators by regulating prostaglandin E(2) and cytokines. World J. Gastroenterol. 2009, 15, 5549–5557.
  37. Lucas, J.L.; Mirshahpanah, P.; Haas-Stapleton, E.; Asadullah, K.; Zollner, T.M.; Numerof, R.P. Induction of Foxp3+ regulatory T cells with histone deacetylase inhibitors. Cell. Immunol. 2009, 257, 97–104.
  38. n-Butyrate Anergized Effector CD4+ T Cells Independent of Regulatory T cell Generation or Activity—Fontenelle—2012—Scandinavian Journal of Immunology—Wiley Online Library. Available online: https://onlinelibrary.wiley.com/doi/10.1111/j.1365-3083.2012.02740.x (accessed on 9 April 2023).
  39. Silva, Y.P.; Bernardi, A.; Frozza, R.L. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol. 2020, 11, 25.
  40. Medzhitov, R. Inflammation 2010: New adventures of an old flame. Cell 2010, 140, 771–776.
  41. Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2017, 9, 7204–7218.
  42. Kuriakose, T.; Kanneganti, T.-D. Pyroptosis in Antiviral Immunity. Curr. Top. Microbiol. Immunol. 2019, 13, 1–19.
  43. Zhang, G.; Wang, J.; Zhao, Z.; Xin, T.; Fan, X.; Shen, Q.; Raheem, A.; Lee, C.R.; Jiang, H. Regulated necrosis, a proinflammatory cell death, potentially counteracts pathogenic infections. Cell Death Dis. 2022, 13, 637.
  44. Patankar, J.V.; Becker, C. Cell death in the gut epithelium and implications for chronic inflammation. Nat. Rev. Gastroenterol. Hepatol. 2020, 17, 543–556.
  45. Machiels, K.; Joossens, M.; Sabino, J.; De Preter, V.; Arijs, I.; Eeckhaut, V.; Ballet, V.; Claes, K.; Van Immerseel, F.; Verbeke, K.; et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 2014, 63, 1275–1283.
  46. Pascal, V.; Pozuelo, M.; Borruel, N.; Casellas, F.; Campos, D.; Santiago, A.; Martinez, X.; Varela, E.; Sarrabayrouse, G.; Machiels, K.; et al. A microbial signature for Crohn’s disease. Gut 2017, 66, 813–822.
  47. De Preter, V.; Arijs, I.; Windey, K.; Vanhove, W.; Vermeire, S.; Schuit, F.; Rutgeerts, P.; Verbeke, K. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway. Inflamm. Bowel Dis. 2012, 18, 1127–1136.
  48. Singh, N.; Gurav, A.; Sivaprakasam, S.; Brady, E.; Padia, R.; Shi, H.; Thangaraju, M.; Prasad, P.D.; Manicassamy, S.; Munn, D.H.; et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 2014, 40, 128–139.
  49. Arpaia, N.; Campbell, C.; Fan, X.; Dikiy, S.; van der Veeken, J.; deRoos, P.; Liu, H.; Cross, J.R.; Pfeffer, K.; Coffer, P.J.; et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature 2013, 504, 451–455.
  50. Smith, P.M.; Howitt, M.R.; Panikov, N.; Michaud, M.; Gallini, C.A.; Bohlooly-Y, M.; Glickman, J.N.; Garrett, W.S. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science 2013, 341, 569–573.
  51. Lee, S.U.; In, H.J.; Kwon, M.S.; Park, B.; Jo, M.; Kim, M.-O.; Cho, S.; Lee, S.; Lee, H.-J.; Kwak, Y.S.; et al. β-Arrestin 2 mediates G protein-coupled receptor 43 signals to nuclear factor-κB. Biol. Pharm. Bull. 2013, 36, 1754–1759.
  52. Chen, W.; Liu, F.; Ling, Z.; Tong, X.; Xiang, C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS ONE 2012, 7, e39743.
  53. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252.
  54. Macia, L.; Tan, J.; Vieira, A.T.; Leach, K.; Stanley, D.; Luong, S.; Maruya, M.; Ian McKenzie, C.; Hijikata, A.; Wong, C.; et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nat. Commun. 2015, 6, 6734.
  55. Xiu, W.; Chen, Q.; Wang, Z.; Wang, J.; Zhou, Z. Microbiota-derived short chain fatty acid promotion of Amphiregulin expression by dendritic cells is regulated by GPR43 and Blimp-1. Biochem. Biophys. Res. Commun. 2020, 533, 282–288.
  56. Yang, W.; Yu, T.; Huang, X.; Bilotta, A.J.; Xu, L.; Lu, Y.; Sun, J.; Pan, F.; Zhou, J.; Zhang, W.; et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat. Commun. 2020, 11, 4457.
  57. Wong, S.H.; Yu, J. Gut microbiota in colorectal cancer: Mechanisms of action and clinical applications. Nat. Rev. Gastroenterol. Hepatol. 2019, 16, 690–704.
  58. Castellarin, M.; Warren, R.L.; Freeman, J.D.; Dreolini, L.; Krzywinski, M.; Strauss, J.; Barnes, R.; Watson, P.; Allen-Vercoe, E.; Moore, R.A.; et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012, 22, 299–306.
  59. Wang, T.; Cai, G.; Qiu, Y.; Fei, N.; Zhang, M.; Pang, X.; Jia, W.; Cai, S.; Zhao, L. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012, 6, 320–329.
  60. Meira, L.B.; Bugni, J.M.; Green, S.L.; Lee, C.-W.; Pang, B.; Borenshtein, D.; Rickman, B.H.; Rogers, A.B.; Moroski-Erkul, C.A.; McFaline, J.L.; et al. DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J. Clin. Investig. 2008, 118, 2516–2525.
  61. Matthews, G.M.; Howarth, G.S.; Butler, R.N. Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism. Chemotherapy 2012, 58, 102–109.
  62. Davie, J.R. Inhibition of histone deacetylase activity by butyrate. J. Nutr. 2003, 133, 2485S–2493S.
  63. Tang, Y.; Chen, Y.; Jiang, H.; Robbins, G.T.; Nie, D. G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int. J. Cancer 2011, 128, 847–856.
  64. Yan, Q.; Gu, Y.; Li, X.; Yang, W.; Jia, L.; Chen, C.; Han, X.; Huang, Y.; Zhao, L.; Li, P.; et al. Alterations of the Gut Microbiome in Hypertension. Front. Cell. Infect. Microbiol. 2017, 7, 381.
  65. Yang, T.; Magee, K.L.; Colon-Perez, L.M.; Larkin, R.; Liao, Y.-S.; Balazic, E.; Cowart, J.R.; Arocha, R.; Redler, T.; Febo, M.; 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. 2019, 226, e13256.
  66. Pluznick, J.L.; Protzko, R.J.; Gevorgyan, H.; Peterlin, Z.; Sipos, A.; Han, J.; Brunet, I.; Wan, L.-X.; Rey, F.; Wang, T.; et al. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proc. Natl. Acad. Sci. USA 2013, 110, 4410–4415.
  67. Natarajan, N.; Hori, D.; Flavahan, S.; Steppan, J.; Flavahan, N.A.; Berkowitz, D.E.; Pluznick, J.L. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41. Physiol. Genom. 2016, 48, 826–834.
  68. Lal, S.; Kirkup, A.J.; Brunsden, A.M.; Thompson, D.G.; Grundy, D. Vagal afferent responses to fatty acids of different chain length in the rat. Am. J. Physiol. Gastrointest. Liver Physiol. 2001, 281, G907–G915.
  69. Jie, Z.; Xia, H.; Zhong, S.-L.; Feng, Q.; Li, S.; Liang, S.; Zhong, H.; Liu, Z.; Gao, Y.; Zhao, H.; et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun. 2017, 8, 845.
  70. Aguilar, E.C.; Leonel, A.J.; Teixeira, L.G.; Silva, A.R.; Silva, J.F.; Pelaez, J.M.N.; Capettini, L.S.A.; Lemos, V.S.; Santos, R.A.S.; Alvarez-Leite, J.I. Butyrate impairs atherogenesis by reducing plaque inflammation and vulnerability and decreasing NFκB activation. Nutr. Metab. Cardiovasc. Dis. 2014, 24, 606–613.
  71. Ley, R.E.; Bäckhed, F.; Turnbaugh, P.; Lozupone, C.A.; Knight, R.D.; Gordon, J.I. Obesity alters gut microbial ecology. Proc. Natl. Acad. Sci. USA 2005, 102, 11070–11075.
  72. Kim, K.N.; Yao, Y.; Ju, S.Y. Short Chain Fatty Acids and Fecal Microbiota Abundance in Humans with Obesity: A Systematic Review and Meta-Analysis. Nutrients 2019, 11, 2512.
  73. Müller, M.; Hernández, M.A.G.; Goossens, G.H.; Reijnders, D.; Holst, J.J.; Jocken, J.W.E.; van Eijk, H.; Canfora, E.E.; Blaak, E.E. 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.
  74. Qin, J.; Li, Y.; Cai, Z.; Li, S.; Zhu, J.; Zhang, F.; Liang, S.; Zhang, W.; Guan, Y.; Shen, D.; et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012, 490, 55–60.
  75. Samuel, B.S.; Shaito, A.; Motoike, T.; Rey, F.E.; Backhed, F.; Manchester, J.K.; Hammer, R.E.; Williams, S.C.; Crowley, J.; Yanagisawa, M.; et al. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. USA 2008, 105, 16767–16772.
  76. Chambers, E.S.; Viardot, A.; Psichas, A.; Morrison, D.J.; Murphy, K.G.; Zac-Varghese, S.E.K.; MacDougall, K.; Preston, T.; Tedford, C.; Finlayson, G.S.; et al. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut 2015, 64, 1744–1754.
  77. Larraufie, P.; Martin-Gallausiaux, C.; Lapaque, N.; Dore, J.; Gribble, F.M.; Reimann, F.; Blottiere, H.M. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci. Rep. 2018, 8, 74.
  78. Pingitore, A.; Chambers, E.S.; Hill, T.; Maldonado, I.R.; Liu, B.; Bewick, G.; Morrison, D.J.; Preston, T.; Wallis, G.A.; Tedford, C.; et al. The diet-derived short chain fatty acid propionate improves beta-cell function in humans and stimulates insulin secretion from human islets in vitro. Diabetes Obes. Metab. 2017, 19, 257–265.
  79. Li, G.; Yao, W.; Jiang, H. Short-chain fatty acids enhance adipocyte differentiation in the stromal vascular fraction of porcine adipose tissue. J. Nutr. 2014, 144, 1887–1895.
  80. Hong, Y.-H.; Nishimura, Y.; Hishikawa, D.; Tsuzuki, H.; Miyahara, H.; Gotoh, C.; Choi, K.-C.; Feng, D.D.; Chen, C.; Lee, H.-G.; et al. Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 2005, 146, 5092–5099.
  81. Jocken, J.W.E.; González Hernández, M.A.; Hoebers, N.T.H.; van der Beek, C.M.; Essers, Y.P.G.; Blaak, E.E.; Canfora, E.E. Short-Chain Fatty Acids Differentially Affect Intracellular Lipolysis in a Human White Adipocyte Model. Front. Endocrinol. 2017, 8, 372.
  82. Ge, H.; Li, X.; Weiszmann, J.; Wang, P.; Baribault, H.; Chen, J.-L.; Tian, H.; Li, Y. Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology 2008, 149, 4519–4526.
  83. Al-Lahham, S.; Roelofsen, H.; Rezaee, F.; Weening, D.; Hoek, A.; Vonk, R.; Venema, K. Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur. J. Clin. Investig. 2012, 42, 357–364.
  84. Zhao, Y.; Liu, J.; Hao, W.; Zhu, H.; Liang, N.; He, Z.; Ma, K.Y.; Chen, Z.-Y. Structure-Specific Effects of Short-Chain Fatty Acids on Plasma Cholesterol Concentration in Male Syrian Hamsters. J. Agric. Food Chem. 2017, 65, 10984–10992.
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