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Ulcerative Colitis
Published in Charles Theisler, Adjuvant Medical Care, 2023
Butyrate, a short-chain fatty acid formed in the colon by bacterial fermentation, is a key nutrient for the cells that line the colon. Just as some cells in the body use glucose for fuel, colonic cells require butyrate. Individuals with ulcerative colitis have decreased levels of butyrate in their stool.9
Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
SCFAs are another class of HDAC inhibitors known to impede cancer cell growth (Anantharaju et al., 2017a). SCFAs are produced in humans as a result of gut-microbial activity on dietary fiber components. The most predominantly produced SCFAs are acetate, propionate and butyrate (den Besten et al., 2013). Several studies have shown that butyrate, but not propionate, inhibit HDAC activity more effectively (Silva et al., 2018). Currently, butyrate is being clinically evaluated as an antineoplastic agent not only due to its ability to induce cell cycle arrest, differentiation, and/or apoptosis in cancer cells, but also due to its favorable safety profile in humans (Chen et al., 2003). Mechanistically, gut microbiota–derived butyrate inhibits Class I HDACs, thereby promoting crotonylation of histone-3 (H3) at lysine 18 residue, which subsequently regulates the expression of several genes involved in cells’ proliferation and survival (Fellows et al., 2018). Structure-inhibition relationship (SIR) studies further confirm that butyrate more specifically inhibits Class I HDACs, in particular HDAC3 compared to Class II HDACs such as HDAC7 (Steliou et al., 2012).
Emerging Highlights on Natural Prodrug Molecules with Multifarious Therapeutic Perspectives
Published in Debarshi Kar Mahapatra, Cristóbal Noé Aguilar, A. K. Haghi, Applied Pharmaceutical Practice and Nutraceuticals, 2021
Mojabir Hussen Ansari, Vaibhav Shende, Debarshi Kar Mahapatra
Butyrin (tributyrin), the prodrug of butyric acid, is an essential triglyceride molecule that is naturally present in the butter and also in some butter products. It is a fatty liquid with acrid flavor and is specifically made up of ester of butyric acid and glycerol. Butyrate is also a product achieved by the fermentation process that took place mainly in the distal colon by the microorganism.9 Butyric acid and its derivatives possess notable antimicrobial activities at different concentrations against Salmonella typhimurium and Clostridium perfringens. Butyric acid, when administered alone as a therapeutic agent often shows compromised pharmacological activity (particularly, short half-life) as a result of rapid metabolism.10 In addition to it, the strong odor of butyrate hinders patient compliance; therefore, direct oral consumption of butyric acid is unacceptable. Although in a study, it was found that the best antimicrobial inhibition was reported by butyric acid and its derivative without the addition of lipase.11 Although focusing on veterinarian applications, recently, it has been discovered that the glycerides and individual administration of butyrin in broiler chickens feed concurrently extends the carcass weight and breast meat. Butyrate improves the epithelization process and brings about collagen lysis by reducing the matrix metalloproteinase release.12
Tight junctions: from molecules to gastrointestinal diseases
Published in Tissue Barriers, 2023
Aekkacha Moonwiriyakit, Nutthapoom Pathomthongtaweechai, Peter R. Steinhagen, Papasara Chantawichitwong, Wilasinee Satianrapapong, Pawin Pongkorpsakol
Many short-chain fatty acids (e.g., butyrate, acetate, and propionate) have been revealed to promote the alteration of TJ permeability by activating lipoxygenase (LOX) in the small intestinal epithelium.265,266 Butyrate is commonly found in bacterial fermentation, which is a by-product of dietary fiber in the large intestine.267 Several benefits of butyrate have been reported, including enhancing the permeability of the intestinal barrier through upregulating claudin-1 transcription, which is related to the association between SP1 and claudin-1 promoter.268 In addition, butyrate was shown to protect against Campylobacter jejuni invasion and translocation across Caco-2 cell monolayers.269 Indeed, the mechanism of action of butyrate in facilitating TJ assembly and maintaining the intestinal barrier in Caco-2 cell monolayers was shown to be dependent on AMPK.270 In addition, a recent study showed that short-chain fatty acids can act as ligands of G-protein-coupled receptors (GPCRs), such as GPR41, GPR43, and GPR109A, to activate PKCβ that can in turn phosphorylate ZO-1 in order to increase intestinal barrier function.271
Fecal microbiota and bile acids in IBD patients undergoing screening for colorectal cancer
Published in Gut Microbes, 2022
Aonghus Lavelle, Stéphane Nancey, Jean-Marie Reimund, David Laharie, Philippe Marteau, Xavier Treton, Matthieu Allez, Xavier Roblin, Georgia Malamut, Cyriane Oeuvray, Nathalie Rolhion, Xavier Dray, Dominique Rainteau, Antonin Lamaziere, Emilie Gauliard, Julien Kirchgesner, Laurent Beaugerie, Philippe Seksik, Laurent Peyrin-Biroulet, Harry Sokol
In contrast, Agathobacter, (formerly Eubacterium rectale28) is a butyrate-producing bacteria that has been shown to be reduced in UC29,30 and has been associated with improved response to anti-TNF medications in pediatric IBD.31 Butyrate is an important short chain fatty acid produced by fermentation of dietary fiber and has immune-modulating anti-inflammatory and anti-neoplastic effects in the colon.32 This genus was strongly associated with C.1. The closely related genus Roseburia was also highest in C.1 (Figure 6a), suggesting that these members of the Lachnospiraceae may be important for the maintenance of gut health in patients with long-standing ulcerative colitis. DMM models, used as an exploratory technique here, have been used to identify different risk groups for development of atopy in a new birth cohort of infants33 and have also been applied to identify microbiota and metabolomic groups in pediatric IBD patients and their relatives.34
The state of the art of fetal hemoglobin-inducing agents
Published in Expert Opinion on Drug Discovery, 2022
Aline Renata Pavan, Juliana Romano Lopes, Jean Leandro Dos Santos
The potential effect of HDAC inhibitors on SCA was first demonstrated for sodium butyrate in 1978. This short-chain fatty acid increases the level of histone acetylation due to the non-selective inhibition of HDAC [30]. Between the late 1980s and early 1990s, butyrate derivatives and other short-chain fatty acids were studied for their application in hemoglobinopathies because these compounds can induce γ-globin and HbF in human erythroid cultures (in vitro) and animals (adult baboons) and patients with β-thalassemia (in vivo) [31–35]. In the 1990s, several dose regimens using butyrates were proposed for hemoglobinopathies. Among them, studies on the prolonged administration of low doses for seven weeks in patients with β-globin disorders [36], the continuous infusion at high doses (2,000 mg/Kg/d) for 10 weeks in β-thalassemia and healthy individuals [37], and the continuous administration at high doses (1,000 mg/kg) in baboons [38] are well-known. Although these regimens achieved the primary goal for HbF induction, many studies have demonstrated a negative antiproliferative effects of butyrates, which could result in a reduction in the HbF levels. Thus, to circumvent this undesirable effect, a regimen therapy based on a pulsed administration of butyrate was evaluated and showed a remarkable and sustained increase in the HbF levels in all patients [39]. Studies for improving the poor pharmacokinetics, inconvenient intravenous administration, and other drawbacks of butyrate are still being conducted, even after more than 20 years of effort [40,41].