The Experts below are selected from a list of 2127 Experts worldwide ranked by ideXlab platform
Sergio A R Paiva - One of the best experts on this subject based on the ideXlab platform.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
Laura E Nagy - One of the best experts on this subject based on the ideXlab platform.
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prophylactic Tributyrin treatment mitigates chronic binge ethanol induced intestinal barrier and liver injury
Journal of Gastroenterology and Hepatology, 2017Co-Authors: Gail A Cresci, Bryan Glueck, Megan R Mcmullen, Wei Xin, Daniella Allende, Laura E NagyAbstract:Background/Aim Impaired gut-liver axis is a potential factor contributing to alcoholic liver disease. Ethanol depletes intestinal integrity and causes gut dysbiosis. Butyrate, a fermentation byproduct of gut microbiota, is altered negatively following chronic ethanol exposure. This study aimed to determine whether prophylactic Tributyrin could protect the intestinal barrier and liver in mice during combined chronic-binge ethanol exposure. Methods C57BL/6 J mice exposed to 5% v/v ethanol-containing diet for 10 days received a single ethanol gavage (5 g/kg) 9 hrs prior to euthanasia. Control mice were isocalorically pair-fed maltose dextrin for ethanol. Diets were supplemented (5 mM) with Tributyrin or glycerol. Intestine and liver disease activity was assessed histologically. Protein and mRNA expression of tight junction proteins (TJ), TLRs and TNFα were assessed. Caco-2 monolayers with/without ethanol exposure and/or sodium butyrate were used to test butyrate's direct effects on intestinal integrity. Results Chronic-binge ethanol feeding impaired intestinal TJ protein co-localization staining; however, Tributyrin co-treatment mitigated these effects. Ethanol depleted TJ and transepithelial electrical resistance in Caco-2 monolayers, but butyrate co-treatment reduced these effects. Hepatic TLR mRNA expression and TNFα protein expression was induced by ethanol; however, the response was significantly dampened in mice co-treated with Tributyrin. Tributyrin altered localization of both neutrophils and single hepatocyte death: leukocytes and apoptotic hepatocytes localized predominantly around the portal tract in ethanol-only treated mice, whereas localization predominated around the central vein in ethanol-Tributyrin mice. Conclusions Prophylactic Tributyrin supplementation mitigated effects of combined chronic-binge ethanol exposure on disruption of intestinal TJ localization and intestinal permeability and liver injury.
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lactobacillus gg and Tributyrin supplementation reduce antibiotic induced intestinal injury
Journal of Parenteral and Enteral Nutrition, 2013Co-Authors: Gail A Cresci, Laura E Nagy, Vadivel GanapathyAbstract:Background: Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or Tributyrin would prevent these changes. Methods: C57BL/6 mice aged 6–8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± Tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate ...
Aline De Conti - One of the best experts on this subject based on the ideXlab platform.
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suppressing activity of Tributyrin on hepatocarcinogenesis is associated with inhibiting the p53 crm1 interaction and changing the cellular compartmentalization of p53 protein
Oncotarget, 2016Co-Authors: Juliana Festa Ortega, Volodymyr Tryndyak, Renato Heidor, Aline De Conti, Kelly Silva Furtado, Paulo L Tavares, Maria Aderuza Horst, Laura Helena Gasparini Fernandes, Marta Pogribna, Svitlana ShpylevaAbstract:Hepatocellular carcinoma (HCC), an aggressive and the fastest growing life-threatening cancer worldwide, is often diagnosed at intermediate or advanced stages of the disease, which substantially limits therapeutic approaches for its successful treatment. This indicates that the prevention of hepatocarcinogenesis is probably the most promising approach to reduce both the HCC incidence and cancer-related mortality. In previous studies, we demonstrated a potent chemopreventive effect of Tributyrin, a butyric acid prodrug, on experimental hepatocarcinogenesis. The cancer-inhibitory effect of Tributyrin was linked to the suppression of sustained cell proliferation and induction of apoptotic cell death driven by an activation of the p53 apoptotic signaling pathway. The goal of the present study was to investigate the underlying molecular mechanisms linked to Tributyrin-mediated p53 activation. Using in vivo and in vitro models of liver cancer, we demonstrate that an increase in the level of p53 protein in nuclei, a decrease in the level of cytoplasmic p53, and, consequently, an increase in the ratio of nuclear/cytoplasmic p53 in rat preneoplastic livers and in rat and human HCC cell lines caused by Tributyrin or sodium butyrate treatments was associated with a marked increase in the level of nuclear chromosome region maintenance 1 (CRM1) protein. Mechanistically, the increase in the level of nuclear p53 protein was associated with a substantially reduced binding interaction between CRM1 and p53. The results demonstrate that the cancer-inhibitory activity of sodium butyrate and its derivatives on liver carcinogenesis may be attributed to retention of p53 and CRM1 proteins in the nucleus, an event that may trigger activation of p53-mediated apoptotic cell death in neoplastic cells.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
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Transcriptomic responses provide a new mechanistic basis for the chemopreventive effects of folic acid and Tributyrin in rat liver carcinogenesis.
International Journal of Cancer, 2014Co-Authors: Aline H. Guariento, Volodymyr Tryndyak, Adriana Campos, Jéssica Carrilho, Elvira Maria Guerra Shinohara, Aline De Conti, Kelly Silva Furtado, Eduardo Purgatto, James C. FuscoeAbstract:The steady increase in the incidence and mortality of hepatocellular carcinoma (HCC) signifies a crucial need to understand better its pathogenesis to improve clinical management and prevention of the disease. The aim of this study was to investigate molecular mechanisms for the chemopreventive effects of folic acid and Tributyrin alone or in combination on rat hepatocarcinogenesis. Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with folic acid and Tributyrin alone or in combination for 5 weeks during promotion stage. Treatment with folic acid and Tributyrin alone or in combination strongly inhibited the development of glutathione-S-transferase placental form (GSTP)-positive foci. Microarray analysis showed significant changes in gene expression. A total of 498, 655 and 940 of differentially expressed genes, involved in cell cycle, p53-signaling, angiogenesis and Wnt pathways, was identified in the livers of rats treated with folic acid, Tributyrin or folic acid and Tributyrin. A detailed analysis of these differentially expressed genes revealed that treatments inhibited angiogenesis in the preneoplastic livers. This was evidenced by the fact that 30 out of 77 differentially expressed genes common to all three treatments are involved in the regulation of the angiogenesis pathway. The inhibition of angiogenesis was confirmed by reduced levels of CD34 protein. In conclusion, the tumor-suppressing activity of folic acid and Tributyrin is associated with inhibition of angiogenesis at early stages of rat liver carcinogenesis. Importantly, the combination of folic acid and Tributyrin has stronger chemopreventive effect than each of the compounds alone.
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the chemopreventive activity of the butyric acid prodrug Tributyrin in experimental rat hepatocarcinogenesis is associated with p53 acetylation and activation of the p53 apoptotic signaling pathway
Carcinogenesis, 2013Co-Authors: Aline De Conti, Volodymyr Tryndyak, Renato Heidor, Igor Koturbash, Joice Kuroiwatrzmielina, Thomas Prates Ong, Frederick A Beland, Fernando Salvador Moreno, Igor P PogribnyAbstract:The reversibility of non-genotoxic phenotypic alterations has been explored in order to develop novel preventive and therapeutic approaches for cancer control. Previously, it has been demonstrated that histone deacetylase (HDAC) inhibitor Tributyrin, a butyric acid prodrug, to have chemopreventive effects on rat hepatocarcinogenesis. The goal of this study was to determine molecular mechanisms associated with the chemopreventive activity of Tributyrin. Male Wistar rats were allocated randomly to untreated control group and two experimental groups. Rats in the experimental group 1 were treated with maltodextrin (3g/kg body wt), and rats in experimental group 2 were treated with Tributyrin (2g/kg body wt) daily for 8 weeks. Two weeks after treatment initiation, rats from experimental groups were subjected to a 'resistant hepatocyte' model of hepatocarcinogenesis. Treatment with Tributyrin resulted in lower HDAC activity and Hdac3 and Hdac4 gene expression, and an increase of histone H3 lysine 9 and 18 and histone H4 lysine 16 acetylation as compared with the experimental group 1. In addition to the increase in histone acetylation, Tributyrin caused an increase in the acetylation of the nuclear p53 protein. These changes were accompanied by a normalization of the p53-signaling network, particularly by the upregulation of pro-apoptotic genes, and a consequent increase of apoptosis and autophagy in the livers of Tributyrin-treated rats. These results indicate that the chemopreventive activity of Tributyrin may be related to an increase of histone and p53 acetylation, which could lead to the induction of the p53 apoptotic pathway.
Renato Heidor - One of the best experts on this subject based on the ideXlab platform.
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suppressing activity of Tributyrin on hepatocarcinogenesis is associated with inhibiting the p53 crm1 interaction and changing the cellular compartmentalization of p53 protein
Oncotarget, 2016Co-Authors: Juliana Festa Ortega, Volodymyr Tryndyak, Renato Heidor, Aline De Conti, Kelly Silva Furtado, Paulo L Tavares, Maria Aderuza Horst, Laura Helena Gasparini Fernandes, Marta Pogribna, Svitlana ShpylevaAbstract:Hepatocellular carcinoma (HCC), an aggressive and the fastest growing life-threatening cancer worldwide, is often diagnosed at intermediate or advanced stages of the disease, which substantially limits therapeutic approaches for its successful treatment. This indicates that the prevention of hepatocarcinogenesis is probably the most promising approach to reduce both the HCC incidence and cancer-related mortality. In previous studies, we demonstrated a potent chemopreventive effect of Tributyrin, a butyric acid prodrug, on experimental hepatocarcinogenesis. The cancer-inhibitory effect of Tributyrin was linked to the suppression of sustained cell proliferation and induction of apoptotic cell death driven by an activation of the p53 apoptotic signaling pathway. The goal of the present study was to investigate the underlying molecular mechanisms linked to Tributyrin-mediated p53 activation. Using in vivo and in vitro models of liver cancer, we demonstrate that an increase in the level of p53 protein in nuclei, a decrease in the level of cytoplasmic p53, and, consequently, an increase in the ratio of nuclear/cytoplasmic p53 in rat preneoplastic livers and in rat and human HCC cell lines caused by Tributyrin or sodium butyrate treatments was associated with a marked increase in the level of nuclear chromosome region maintenance 1 (CRM1) protein. Mechanistically, the increase in the level of nuclear p53 protein was associated with a substantially reduced binding interaction between CRM1 and p53. The results demonstrate that the cancer-inhibitory activity of sodium butyrate and its derivatives on liver carcinogenesis may be attributed to retention of p53 and CRM1 proteins in the nucleus, an event that may trigger activation of p53-mediated apoptotic cell death in neoplastic cells.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
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the chemopreventive activity of butyrate containing structured lipids in experimental rat hepatocarcinogenesis
Molecular Nutrition & Food Research, 2016Co-Authors: Renato Heidor, Juliana Neves Rodrigues Ract, Aline De Conti, Juliana Festa Ortega, Kelly Silva Furtado, Paulo L Tavares, Eduardo Purgatto, Sergio A R Paiva, Roberta Claro Da SilvaAbstract:cope Emerging evidence indicates that the use of bioactive food components is a promising strategy to prevent the development of liver cancer. The goal of this study was to examine the chemopreventive effect of butyrate-containing structured lipids (STLs) produced by an enzymatic interesterification of Tributyrin and flaxseed oil on rat hepatocarcinogenesis. Methods and results Male Wistar rats were subjected to a classic “resistant hepatocyte” model of liver carcinogenesis and treated with STLs, Tributyrin or flaxseed oil during the initial phases of hepatocarcinogenesis. Treatment with STLs and Tributyrin strongly inhibited the development of preneoplastic liver lesions. The chemopreventive activity of Tributyrin was associated with the induction of apoptosis and reduction of the expression of major activated hepatocarcinogenesis-related oncogenes. Treatment with STLs caused substantially greater inhibitory effects than Tributyrin on oncogene expression. Conclusion These results demonstrate that the tumor-suppressing activity of butyrate-containing STLs is associated with its ability to prevent and inhibit activation of major hepatocarcinogenesis-related oncogenes. Enrichment of histone H3K9me3 and H3K27me3 at the promoter of Myc and Ccnd1 genes may be related to the inhibitory effect on oncogene expression in the livers of STL-treated rats.
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the chemopreventive activity of the butyric acid prodrug Tributyrin in experimental rat hepatocarcinogenesis is associated with p53 acetylation and activation of the p53 apoptotic signaling pathway
Carcinogenesis, 2013Co-Authors: Aline De Conti, Volodymyr Tryndyak, Renato Heidor, Igor Koturbash, Joice Kuroiwatrzmielina, Thomas Prates Ong, Frederick A Beland, Fernando Salvador Moreno, Igor P PogribnyAbstract:The reversibility of non-genotoxic phenotypic alterations has been explored in order to develop novel preventive and therapeutic approaches for cancer control. Previously, it has been demonstrated that histone deacetylase (HDAC) inhibitor Tributyrin, a butyric acid prodrug, to have chemopreventive effects on rat hepatocarcinogenesis. The goal of this study was to determine molecular mechanisms associated with the chemopreventive activity of Tributyrin. Male Wistar rats were allocated randomly to untreated control group and two experimental groups. Rats in the experimental group 1 were treated with maltodextrin (3g/kg body wt), and rats in experimental group 2 were treated with Tributyrin (2g/kg body wt) daily for 8 weeks. Two weeks after treatment initiation, rats from experimental groups were subjected to a 'resistant hepatocyte' model of hepatocarcinogenesis. Treatment with Tributyrin resulted in lower HDAC activity and Hdac3 and Hdac4 gene expression, and an increase of histone H3 lysine 9 and 18 and histone H4 lysine 16 acetylation as compared with the experimental group 1. In addition to the increase in histone acetylation, Tributyrin caused an increase in the acetylation of the nuclear p53 protein. These changes were accompanied by a normalization of the p53-signaling network, particularly by the upregulation of pro-apoptotic genes, and a consequent increase of apoptosis and autophagy in the livers of Tributyrin-treated rats. These results indicate that the chemopreventive activity of Tributyrin may be related to an increase of histone and p53 acetylation, which could lead to the induction of the p53 apoptotic pathway.
Gail A M Cresci - One of the best experts on this subject based on the ideXlab platform.
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Tributyrin supplementation protects immune responses and vasculature and reduces oxidative stress in the proximal colon of mice exposed to chronic binge ethanol feeding
Clinical & Developmental Immunology, 2018Co-Authors: Bryan Glueck, Yingchun Han, Gail A M CresciAbstract:Excessive ethanol consumption causes adverse effects and contributes to organ dysfunction. Ethanol metabolism triggers oxidative stress, altered immune function, and gut dysbiosis. The gut microbiome is known to contribute to the maintenance of intestinal homeostasis, and disturbances are associated with pathology. A consequence of gut dysbiosis is also alterations in its metabolic and fermentation byproducts. The gut microbiota ferments undigested dietary polysaccharides to yield short-chain fatty acids, predominantly acetate, propionate, and butyrate. Butyrate has many biological mechanisms of action including anti-inflammatory and immunoprotective effects, and its depletion is associated with intestinal injury. We previously showed that butyrate protects gut-liver injury during ethanol exposure. While the intestine is the largest immune organ in the body, little is known regarding the effects of ethanol on intestinal immune function. This work is aimed at investigating the effects of butyrate supplementation, in the form of the structured triglyceride Tributyrin, on intestinal innate immune responses and oxidative stress following chronic-binge ethanol exposure in mice. Our work suggests that Tributyrin supplementation preserved immune responses and reduced oxidative stress in the proximal colon during chronic-binge ethanol exposure. Our results also indicate a possible involvement of Tributyrin in maintaining the integrity of intestinal villi vasculature disrupted by chronic-binge ethanol exposure.
