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Frontiers in Cellular and Infection... 2022Accumulating evidence suggests that selected microbiota-derived metabolites play a significant role in both tumor prevention and supportive treatment of cancer.... (Review)
Review
Accumulating evidence suggests that selected microbiota-derived metabolites play a significant role in both tumor prevention and supportive treatment of cancer. Short-chain fatty acids (SCFAs), i.e., mainly acetate, proprionate, and butyrate, are one of them. Nowadays, it is known that butyrate is a key microbial metabolite. Therefore, in the current review, we focused on butyrate and sodium butyrate (NaB) in the context of colorectal cancer. Notably, butyrate is characterized by a wide range of beneficial properties/activities. Among others, it influences the function of the immune system, maintains intestinal barrier integrity, positively affects the efficiency of anti-cancer treatment, and may reduce the risk of mucositis induced by chemotherapy. Taking into consideration these facts, we analyzed NaB (which is a salt of butyric acid) and its impact on gut microbiota as well as anti-tumor activity by describing molecular mechanisms. Overall, NaB is available as, for instance, food with special medical purposes (depending on the country's regulation), and its administration seems to be a promising option for colorectal cancer patients.
Topics: Humans; Butyric Acid; Fatty Acids, Volatile; Gastrointestinal Microbiome; Microbiota; Colorectal Neoplasms
PubMed: 36389140
DOI: 10.3389/fcimb.2022.1023806 -
Cell Death & Disease Apr 2023Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce...
Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis and autophagy. However, it remains largely unclear whether butyrate can regulate cell ferroptosis, and the mechanism by which has not been studied. In this study, we found that RAS-selective lethal compound 3 (RSL3)- and erastin-induced cell ferroptosis were enhanced by sodium butyrate (NaB). With regard to the underlying mechanism, our results showed that NaB promoted ferroptosis by inducing lipid ROS production via downregulating the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Moreover, the FFAR2-AKT-NRF2 axis and FFAR2-mTORC1 axis accounts for the NaB-mediated downregulation of SLC7A11 and GPX4, respectively, in a cAMP-PKA-dependent manner. Functionally, we found that NaB can inhibit tumor growth and the inhibitory effect could be eliminated by administrating MHY1485 (mTORC1 activator) and Ferr-1 (ferroptosis inhibitor). Altogether, in vivo results suggest that NaB treatment is correlated to the mTOR-dependent ferroptosis and consequent tumor growth through xenografts and colitis-associated colorectal tumorigenesis, implicating the potential clinical applications of NaB for future colorectal cancer treatments. Based on all these findings, we have proposed a regulatory mechanism via which butyrate inhibits the mTOR pathway to control ferroptosis and consequent tumorigenesis.
Topics: Humans; Butyric Acid; Carcinogenesis; Cell Transformation, Neoplastic; Ferroptosis; Mechanistic Target of Rapamycin Complex 1; TOR Serine-Threonine Kinases
PubMed: 37185889
DOI: 10.1038/s41419-023-05778-0 -
Biomedicine & Pharmacotherapy =... Apr 2023Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the...
BACKGROUND
Alcohol abuse triggers neuroinflammation, leading to neuronal damage and further memory and cognitive impairment. Few satisfactory advances have been made in the management of alcoholic central nervous impairment. Therefore, novel and more practical treatment options are urgently needed. Butyrate, a crucial metabolite of short-chain fatty acids (SCFAs), has been increasingly demonstrated to protect against numerous metabolic diseases. However, the impact of butyrate on chronic alcohol consumption-induced central nervous system (CNS) lesions remains unknown.
METHODS
In this study, we assessed the possible effects and underlying mechanisms of butyrate on the attenuation of alcohol-induced CNS injury in mice. Firstly, sixty female C57BL/6 J mice were randomly divided into 4 groups: pair-fed (PF) group (PF/CON), alcohol-fed (AF) group (AF/CON), PF with sodium butyrate (NaB) group (PF/NaB) and AF with NaB group (AF/NaB). Each group was fed a modified Lieber-DeCarli liquid diet with or without alcohol. After six weeks of feeding, the mice were euthanized and the associated indicators were investigated.
RESULTS
As indicated by the behavioral tests and brain morphology, dietary NaB administration significantly ameliorated aberrant behaviors, including locomotor hypoactivity, anxiety disorder, depressive behavior, impaired learning, spatial recognition memory, and effectively reduced chronic alcoholic central nervous system damage. To further understand the underlying mechanisms, microglia-mediated inflammation and the associated M1/M2 polarization were measured separately. Firstly, pro-inflammatory TNF-α, IL-1β, and IL-6 in brain and peripheral blood circulation were decreased, but IL-10 were increased in the AF/NaB group compared with the AF/CON group. Consistently, the abnormal proportions of activated and resting microglial cells in the hippocampus and cortex regions after excessive alcohol consumption were significantly reduced with NaB treatment. Moreover, the rectification of microglia polarization (M1/M2) imbalance was found after NaB administration via binding GPR109A, up-regulating the expression of PPAR-γ and down-regulating TLR4/NF-κB activation. In addition to the direct suppression of neuroinflammation, intriguingly, dietary NaB intervention remarkably increased the levels of intestinal tight junction protein occludin and gut morphological barrier, attenuated the levels of serum lipopolysaccharide (LPS) and dysbiosis of gut microbiota, suggesting that NaB supplementation effectively improved the integrity and permeability of gut microecology. Finally, the neurotransmitters including differential Tryptophan (Trp) and Kynurenine (Kyn) were found with dietary NaB administration, which showed significantly altered and closely correlated with the gut microbiota composition, demonstrating the complex interactions in the microbiome-gut-brain axis involved in the efficacy of dietary NaB therapy for alcoholic CNS lesions.
CONCLUSION
Dietary microbial metabolite butyrate supplementation ameliorates chronic alcoholic central nervous damage and improves related memory and cognitive functions through suppressing microglia-mediated neuroinflammation by GPR109A/PPAR-γ/TLR4-NF-κB signaling pathway and modulating microbiota-gut-brain axis.
Topics: Mice; Female; Animals; Microglia; Brain-Gut Axis; Neuroinflammatory Diseases; NF-kappa B; Toll-Like Receptor 4; Peroxisome Proliferator-Activated Receptors; Mice, Inbred C57BL; Ethanol; Butyric Acid
PubMed: 36709599
DOI: 10.1016/j.biopha.2023.114308 -
Could the use of butyric acid have a positive effect on microbiota and treatment of type 2 diabetes?European Review For Medical and... Jul 2021This review focuses on the role of butyrate as one of the key metabolites of gut microbiota. Butyrate along with other short-chain fatty acids, acetate and propionate,... (Review)
Review
OBJECTIVE
This review focuses on the role of butyrate as one of the key metabolites of gut microbiota. Butyrate along with other short-chain fatty acids, acetate and propionate, is one of the most important regulators of human metabolism. In this review, we discuss how changes in gut microbiota triggered by type 2 diabetes mellitus and its treatment (e.g., metformin) affect butyrate synthesis, how to increase butyrate production and whether there is robust evidence for the positive effects of sodium butyrate in the treatment of diabetes mellitus.
MATERIALS AND METHODS
Literature review was conducted by all authors. Studies published until 27/03/2020 were included. Search words were: ("butyric acid" OR "butyrate") AND ("type 2 diabetes "OR "T2DM"). The articles selected for the study were not chosen in a systematic manner, so the evidence may not be comprehensive.
RESULTS
Butyrate was found to effectively reduce inflammation and plays a prominent role in the function of the intestinal barrier. To date the use of sodium butyrate in the treatment of patients with T2DM is not very popular. Meanwhile, butyric acid can beneficially modulate intestinal functions, counteracting the negative effects of the disease as well as the drugs used to treat diabetes.
CONCLUSIONS
T2DM is a widespread chronic disease. Understanding role of microbiota in type 2 diabetes and the mechanisms connecting T2DM and alterations in gut microbiota could be the key to improved treatment of T2DM.
Topics: Butyric Acid; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Metformin
PubMed: 34286509
DOI: 10.26355/eurrev_202107_26250 -
FEMS Microbiology Letters Apr 2016Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals... (Review)
Review
Fermentation-based production of butyric acid is robust and efficient. Modern catalytic technologies make it possible to convert butyric acid to important fine chemicals and biofuels. Here, current chemocatalytic and biocatalytic conversion methods are reviewed with a focus on upgrading butyric acid to 1-butanol or butyl-butyrate. Supported Ruthenium- and Platinum-based catalyst and lipase exhibit important activities which can pave the way for more sustainable process concepts for the production of green fuels and chemicals.
Topics: 1-Butanol; Biocatalysis; Biofuels; Bioreactors; Butyric Acid; Carboxylic Acids; Clostridium tyrobutyricum; Esterification; Fermentation; Ion Exchange; Ion Exchange Resins; Lipase
PubMed: 26994015
DOI: 10.1093/femsle/fnw064 -
International Journal of Molecular... Sep 2021Intestinal dysfunction of farm animals, such as intestinal inflammation and altered gut microbiota, is the critical problem affecting animal welfare, performance and... (Review)
Review
Intestinal dysfunction of farm animals, such as intestinal inflammation and altered gut microbiota, is the critical problem affecting animal welfare, performance and farm profitability. China has prohibited the use of antibiotics to improve feed efficiency and growth performance for farm animals, including poultry, in 2020. With the advantages of maintaining gut homeostasis, enhancing digestion, and absorption and modulating gut microbiota, organic acids are regarded as promising antibiotic alternatives. Butyric and citric acids as presentative organic acids positively impact growth performance, welfare, and intestinal health of livestock mainly by reducing pathogenic bacteria and maintaining the gastrointestinal tract (GIT) pH. This review summarizes the discovery of butyric acid (BA), citric acid (CA) and their salt forms, molecular structure and properties, metabolism, biological functions and their applications in poultry nutrition. The research findings about BA, CA and their salts on rats, pigs and humans are also briefly reviewed. Therefore, this review will fill the knowledge gaps of the scientific community and may be of great interest for poultry nutritionists, researchers and feed manufacturers about these two weak organic acids and their effects on intestinal health and gut microbiota community, with the hope of providing safe, healthy and nutrient-rich poultry products to consumers.
Topics: Animal Feed; Animals; Butyric Acid; Citric Acid; Gastrointestinal Microbiome; Intestinal Mucosa; Poultry
PubMed: 34638730
DOI: 10.3390/ijms221910392 -
Ecotoxicology and Environmental Safety Mar 2023After intensive research on the gut-brain axis, intestinal dysbiosis is considered to be one of the important pathways of cognitive decline. Microbiota transplantation...
After intensive research on the gut-brain axis, intestinal dysbiosis is considered to be one of the important pathways of cognitive decline. Microbiota transplantation has long been thought to reverse the behavioral changes in the brain caused by colony dysregulation, but in our study, microbiota transplantation seemed to improve only behavioral brain function, and there was no reasonable explanation for the high level of hippocampal neuron apoptosis that remained. Butyric acid is one of the short-chain fatty acids of intestinal metabolites and is mainly used as an edible flavoring. It is commonly used in butter, cheese and fruit flavorings, and is a natural product of bacterial fermentation of dietary fiber and resistant starch in the colon, acting similarly to the small-molecule HDAC inhibitor TSA. The effect of butyric acid on HDAC levels in hippocampal neurons in the brain remains unclear. Therefore, this study used rats with low bacterial abundance, conditional knockout mice, microbiota transplantation, 16S rDNA amplicon sequencing, and behavioral assays to demonstrate the regulatory mechanism of short-chain fatty acids on the acetylation of hippocampal histones. The results showed that disturbance of short-chain fatty acid metabolism led to high HDAC4 expression in the hippocampus and regulated H4K8ac, H4K12ac, and H4K16ac to promote increased neuronal apoptosis. However, microbiota transplantation did not change the pattern of low butyric acid expression, resulting in maintained high HDAC4 expression in hippocampal neurons with continued neuronal apoptosis. Overall, our study shows that low levels of butyric acid in vivo can promote HDAC4 expression through the gut-brain axis pathway, leading to hippocampal neuronal apoptosis, and demonstrates that butyric acid has great potential value for neuroprotection in the brain. In this regard, we suggest that patients with chronic dysbiosis should pay attention to changes in the levels of SCFAs in their bodies, and if deficiencies occur, they should be promptly supplemented through diet and other means to avoid affecting brain health.
Topics: Mice; Rats; Animals; Butyric Acid; Dysbiosis; Gastrointestinal Microbiome; Fatty Acids, Volatile; Bacteria; Hippocampus; Apoptosis; Histone Deacetylases
PubMed: 36812872
DOI: 10.1016/j.ecoenv.2023.114660 -
Swiss Medical Weekly 2012In this brief review, we present some data from the literature on butyric acid and some of its more interesting potential uses, especially in the field of... (Review)
Review
In this brief review, we present some data from the literature on butyric acid and some of its more interesting potential uses, especially in the field of gastroenterology. Due to its principal characteristics, butyric acid is primarily used for pathologies of the colon (functional, inflammatory). Although only preliminary data are available, butyric acid may also have interesting extraintestinal applications, such as in the treatment of haematological, metabolic, and neurological pathologies.
Topics: Butyric Acid; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Obesity; Urea Cycle Disorders, Inborn; beta-Thalassemia
PubMed: 22674349
DOI: 10.4414/smw.2012.13596 -
Gut Oct 1987Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the...
Evidence for the occurrence of microbial breakdown of carbohydrate in the human colon has been sought by measuring short chain fatty acid (SCFA) concentrations in the contents of all regions of the large intestine and in portal, hepatic and peripheral venous blood obtained at autopsy of sudden death victims within four hours of death. Total SCFA concentration (mmol/kg) was low in the terminal ileum at 13 +/- 6 but high in all regions of the colon ranging from 131 +/- 9 in the caecum to 80 +/- 11 in the descending colon. The presence of branched chain fatty acids was also noted. A significant trend from high to low concentrations was found on passing distally from caecum to descending colon. pH also changed with region from 5.6 +/- 0.2 in the caecum to 6.6 +/- 0.1 in the descending colon. pH and SCFA concentrations were inversely related. Total SCFA (mumol/l) in blood was, portal 375 +/- 70, hepatic 148 +/- 42 and peripheral 79 +/- 22. In all samples acetate was the principal anion but molar ratios of the three principal SCFA changed on going from colonic contents to portal blood to hepatic vein indicating greater uptake of butyrate by the colonic epithelium and propionate by the liver. These data indicate that substantial carbohydrate, and possibly protein, fermentation is occurring in the human large intestine, principally in the caecum and ascending colon and that the large bowel may have a greater role to play in digestion than has previously been ascribed to it.
Topics: Acetates; Acetic Acid; Animals; Butyrates; Butyric Acid; Fatty Acids; Female; Fermentation; Gastrointestinal Contents; Hepatic Veins; Humans; Hydrogen-Ion Concentration; Intestine, Large; Male; Portal Vein; Propionates; Swine
PubMed: 3678950
DOI: 10.1136/gut.28.10.1221 -
Nutricion Hospitalaria Oct 2017Short chain fatty acids contain up to 6 carbon atoms. Among them, butyric acid stands out for its key role in pathologies with intestinal affectation. Butyric acid is... (Review)
Review
INTRODUCTION
Short chain fatty acids contain up to 6 carbon atoms. Among them, butyric acid stands out for its key role in pathologies with intestinal affectation. Butyric acid is the main energetic substrate of the colonocyte, it stimulates the absorption of sodium and water in the colon, and presents trophic action on the intestinal cells.
OBJECTIVES
To review the clinical use of formulations for the oral use of butyric acid.
METHODS
Review of published articles on oral supplementation with butyric acid in intestinal pathologies.
RESULTS
The publications mainly deal with the use of oral butyric acid in pathologies involving inflammation and / or alterations of intestinal motility. Highlighting the clinical potential in inflammatory bowel diseases and irritable bowel syndrome.
CONCLUSION
The use of oral supplementation with butyric acid is a promising strategy in pathologies such as inflammatory bowel diseases and irritable bowel syndrome. Bio-available butyric acid formulations with acceptable organoleptic characteristics are being advanced.
Topics: Butyric Acid; Fatty Acids, Volatile; Humans; Intestinal Diseases
PubMed: 29156934
DOI: 10.20960/nh.1573