MetaBiom
Microbiome & Chronic Diseases

Evidence Based Medicine
Sign in

Short Chain Fatty Acid ⇒ Butyrate {60000044}

Record Keys


Parent:
Definition:
Butyrate
Queue:[  ]

Details


Initialisation date:
2020-09-17
Specification:
[  ]
Source:
[  ]

Links


Meta Information


Structural Type:
Fatty acid
Functional Type:
Energy Source
Function:
Immun regulator, Anti-inflammatory, Anti-cancer, Antioxidant, Anti-atherosclerosis, Anti-angiogenesis, Anti-obesity, Enhancing Gut integrity, Microbiome modulator

Notes:


- Mechanisms involved in gut microbiota-host communication. Short-chain fatty acids (SCFAs), mainly propionate, acetate, and butyrate, stimulate Fox3+ Tregs and macrophages via GPR43 activation and HDAC inhibition. Fox3+ Tregs subsequently produce the anti-inflammatory cytokine IL-10, while proinflammatory cytokines such as IL-6 and IL-12 are secreted by macrophages. Moreover, Th17 cells and effector memory T cells were downregulated by SCFAs. By suppressing PPARγ, SCFAs promote lipid oxidation. Although insulin production was enhanced by SCFAs, glycogenolysis and gluconeogenesis were both observed to occur even with SCFA treatment. L-carnitine and choline consumption contribute to the release of trimethylamine (TMA), which is then converted by FMO into trimethylamine N-oxide (TMAO). Both SCFAs and TMAO activate the NLRP3 inflammasome, leading to IL-18 and IL-1β release. Through the MAPK/NF-κB signalling pathway, TMAO increases the levels of COX2, IL-6, and ICAM1. Secondary bile acids such as deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) are produced in the intestine by gut microbiota and then participate in inflammatory modulation and blood sugar regulation. (3)

References Notes


[  ]

Shared Reference Notes


  • [1.39
    - Butyrate is the primary energy source of colonic epithelial cells, and adequate levels aid in maintaining barrier function. - Butyrate is essential in the maintenance of gastrointestinal health through inhibition of pro-inflammatory pathways and the reduction of oxidative stress within the colon.
  • [1.40
    - Butyrate is able to strongly inhibit the production of proinflammatory cytokines IL-12 and TNF-alpha by monocytes, whereas the anti-inflammatory cytokine IL-10 is significantly increased after bacterial stimulation. - Activation of Tregs by butyrate not only inhibits effector T cells but also produces the anti-inflammatory cytokine IL-10
  • [1.41
    - Butyrate, upregulate the Vitamin D Receptor signaling
  • [1.42] [#Crohn’s disease
    - Comprehensive overview of functional dysbiosis in the gut microbiome during IBD activity showed increases in facultative anaerobes, such as E. coli which correlates with inflammation status, and decreases in obligate anaerobes, such as Faecalibacterium prausnitzii and Roseburia hominis -The results of the present study confirmed decreases in the abundance of Firmicutes and Bacteroidetes, increases in Enterobacteriaceae, Pasteurellaceae, and Veillonellaceae and the presence of Fusobacterium in stool samples of CD patients. - Butyrate-producing bacteria are depleted in IBD patients, and probiotic treatment with these bacteria has therapeutic potential. - A higher proportion of Lachnospiraceae in donor stool was associated with a higher success rate of FMT [85], and recipients that responded to FMT exhibited increases in butyrate-producing Lachnospiraceae and Ruminococcaceae. - The reduced SCFA levels in patients with IBD result from lower abundance of SCFA-producing bacteria, especially those of the phylum Firmicutes. -- Butyrate can act as an energy source for normal colon epithelial cells, promoting their proliferation, but can also inhibit proliferation and induce apoptosis.
  • [1.43
    - Butyrate suppress proinflammatory factors, including IL-6, IL-12, and NO, from intestinal macrophages by HDAC inhibition. - Butyrate restore bile acid dysregulation and counteract hepatic inflammation.
  • [1.33
    - Dietary prebiotics, which can be metabolized by bacteria to produce butyrate, can be an intriguing new investigational approach to prevent #Immunotherapy-induced colitis and lead to improved patient outcomes. - Butyrate is a gut-microbiome-derived, anti-inflammatory metabolite that could be protective against ICI colitis, based on data from other forms of colitis. - #Dietary prebiotic starches that can increase butyrate production are a promising method of microbial manipulation that could be used to mitigate ICI colitis.
  • [1.27
    - Butyrate are restricted to certain microorganisms belonging to the phylum Firmicutes or Akkermansia muciniphilla
  • [1.44
    - The TCA cycle is dysregulated in colonocytes, due to the lack of butyrate. However, upon supplementation of butyrate, isolated colonocytes from a germ-free mouse dramatically increased mitochondrial respiration.
  • [1.45] [#Low fibre Diet
    - Butyrate-producing bacteria, like those belonging to Bacteroidetes and Firmicutes phylum, exert their anti-inflammatory activity metabolizing dietary fibers: A low-fiber diet leads to reduced production of butyrate, which acts as a negative regulator of pro-inflammatory pathways and enhances the intestinal barrier function. - When Fibre is scarce, intestinal bacteria use the intestinal mucus as a nutrient, which leads to inflammation through close contact between bacteria and the epithelial layer.
  • [1.34
    - The gut microbiota of moderate and severe #Covid-19 patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera.
  • [1.46] [#Alzheimer’s disease
    - Colonization of the C. elegans gut with enteric bacterial pathogens disrupted proteostasis in the intestine, muscle, neurons, and the gonad. - The presence of bacteria that conditionally synthesize butyrate, a molecule previously shown to be beneficial in neurodegenerative disease models, suppressed aggregation and the associated proteotoxicity.
  • [1.47] [#Alzheimer’s disease] [#Keto diet
    - MD-ketogenic diet improved the AD biomarkers viz. amyloid and tau proteins in the cerebrospinal fluids of MCI patients, wherein these changes linked with increased gut butyrate. - There is a significant reduction in Aβ levels and increase in behavioral responses after 12-weeks of sodium butyrate supplementation in mouse
  • [1.48
    - The SCFA receptor known as GPR109a is expressed on innate immune cells, adipocytes, and intestinal epithelial cells to respond to butyrate and niacin (vitamin B3), reducing inflammatory responses
  • - Butyrate was shown to rescue decreased GLP-1 receptor expression in the liver and decrease inflammation
  • [1.49
    - Increases in butyrate with increases in insulin and glucose, and decreases in HDL cholesterol and ghrelin.
  • [1.50
    - #Fusobacterium, utilizes different pathways like those for Glutamate (4-aminobutyrate) and Lysine for butyrate production, which are associated with a release of harmful byproducts like ammonia.
  • [1.51
    - Butyrate suppresses proinflammatory genes and tumor growth, the latter via histone deacetylase inhibition, which downregulates oncogenic signaling pathways.
  • [1.52] [#Diabetes Type 2
  • [#Eosinophilic esophagitis] - Butyrate > restore the barrier function of esophageal epithelial cells after an inflammatory insult
  • [1.54] [#Covid-19
  • [1.28
    - Butyrate > critical regulator of intestinal barrier integrity and mucosal immune homeostasis. - Eubacterium rectale, Faecalibacterium prausnitzii, and Anaerostipes coli S22/1 > main butyrate producers
  • [1.55] [#Alzheimer’s disease
    - Butyrate can reduce AD by affecting the #P-glycoprotein pathway
  • - Butyrate > robust anticancer ability in various #Cancer cell cultures and mouse models. - It can effectively promote #Cancer cell apoptosis and reduce cell proliferation capacity and activity through different signaling pathways
  • [1.56
    - Butyrate administration to mothers > renders newborn mice resistant to inflammation and injury of bile ducts > improves survival. - Bacteroidetes and Clostridia and increases glutamate/#Glutamine and hypoxanthine in stool metabolites of newborn mice > prevention of hepatic immune cell activation and survival. - In human neonates with #Biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/#Glutamine and increased hypoxanthine pathways. - The direct administration of butyrate or #Glutamine to newborn mice attenuates the disease phenotype, but only #Glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells.
  • [1.57] [#Short Chain Fatty Acid
    - butyrate or #Propionate, but not acetate > rapidly converted to the corresponding acyl-CoAs > used by p300 to catalyze auto-acylation of the autoinhibitory loop > activate the acetyltransferase p300 > activating the enzyme for histone/protein acetylation > rapid and sustained increases in histone acetylation.
  • [1.26] [#Sleep Deprivation
    - fecal butyrate concentrations positively correlated with the relative abundance of #Butyricimonas. - the abundance of SCFAs-producing microbes, such as #Butyricicoccus, #Butyricimonas, and #Alistipes markedly decreased after SD. - butyrate > significantly reduced after 48 h of SD > After 1 week of sleep recovery, butyrate concentrations returned.
  • [#Sleep Deprivation] - #Streptococcus was negatively correlated with the concentration of fecal butyrate and positively correlated with the KEGG pathway of #Lipopolysaccharide biosynthesis.
  • [1.58
    - butyrate plays a role in regulating immune response via expansion of Treg cell populations, which is suggestive of a role for SCFA in ameliorating pro-inflammatory responses of immune cells to antigenic stimuli. - #Faecalibacterium prausnitzii, help maintain homeostasis through production of SCFAs (butyrate) and modulation of downstream inflammatory pathways through potential induction of a tolerogenic cytokine profile (e.g., low secretion of proinflammatory and elevated secretion of anti-inflammatory cytokines)
  • [1.38
    - Butyrate inhibits gut microbiome #Bacteroides - Butyrate inhibition depends on which #Sugar a given #Bacteroides strain uses - Core genome variation in Acyl-CoA enzymes mediates butyrate defense - Each #Bacteroides unique fitness landscape unpredictable by interaction of ecosystem parts
  • [1.6] [#Gout
  • [1.2] [#Behcet’s Disease
  • [1.8] [#Amyotrophic lateral sclerosis
    - The gut microbial communities of the ALS patients were more diverse and were deficient in #Prevotella spp. compared with those of their spouses. - Predictive analysis of microbial enzymes revealed that ALS patients had decreased activity in several metabolic pathways, including carbon metabolism, butyrate metabolism, and systems involving histidine kinase and response regulators.
  • [1.59] [#Chronic kidney disease
    - Bacterial species involved in butyrate production, #Indole synthesis and mucin degradation were also related to CKD.
  • [1.32
    - #Firmicutes and #Bacteroides are the main butyrate producing phyla
  • - Butyrate exhibits a broad range of pharmacological activities, including microbiome modulator, anti-inflammatory, anti-obesity, metabolic pathways regulator, anti-angiogenesis, and antioxidant. - Butyrate is a four-carbon SCFA, mainly known as a fuel for colonocytes. In addition to dietary fibers especially resistant starch, which is an indirect source of butyrate, some types of cheese, butter, and milk also contain small amounts of butyrate.
  • - Butyrate could induce adipogenesis by activating PPARγ, which is supported by several studies. Adipogenesis is associated with reduced inflammatory and oxidative molecules production in adipose tissue, organs lipotoxicity and IR
  • [#Heart failure] [#Eubacterium hallii, #Lachnospiraceae, #Ruminococcaceae] - patients with HF have a decrease in butyrate-producing bacteria, especially, Lachnospiracea and Ruminococcacea families. - reduction of the butyrate-producing Eubacterium Halli and Lachnospiracea is correlated with increased inflammation, severity of disease, heart damage and mortality
  • - butyrate, a fermentation product of gut microbiota, can regulate tight junction protein expression and influence histone deacetylase activity of BBB epigenetically.
  • [#Serotonin (5-hydroxytryptamine)] - bacterial SCFA-butyrate regulates the biosynthesis of serotonin, which is responsible for initiating peristalsis.
  • [1.7] [#Parkinson’s Disease] [#Indole-3-propionic acid (IPA), #Short Chain Fatty Acid
    - in PD Patient > Fecal SCFA levels of butyric acid, #Valeric acid and propionic acid are reduced, whereas plasma levels were higher. - in PD Patient > Low fecal concentration of most SCFAs > increased plasma propionic acid concentration > More severe motor impairment - in PD Patient > Low fecal levels of butyric acid and higher plasma concentrations of butyric acid and #Valeric acid > More serious cognitive symptoms.
  • [1.61
    - butyrate has been shown to be a potential therapeutic strategy for #Atherosclerosis, specifically by its promoting cholesterol efflux through upregulation of ABCA1 expression in macrophages, thereby ameliorating #Atherosclerosis.
  • - children with #Autism, SCFA levels were differentially altered, with an increase in #Propionate and #Acetate and a decrease in butyrate levels. - rats fed with #Propionate exhibited phenotypic features similar to those of #Autism.
  • - butyrate has a direct impact on the intestine, promoting intestinal barrier function, accelerating repair of intestinal epithelial cell damage, and maintaining intestinal homeostasis.
  • [#Diabetes Type 2] - butyrate has also been shown to increase diverse circulating glucose-regulating hormones by promoting intestinal expression of GLP-1, ultimately lowering blood glucose levels.
  • [#Hypertension] - Blood pressure > increased #Acetate, butyrate, and #Propionate
  • [1.62
    - #Faecalibacterium prausnitzii, member of Clostridium leptum subgroup, representing more than 5% of the total gut microbiota in healthy humans, is one of the most abundant #Butyric acid producing bacteria of the gut microbiome. It favorably modulates intestinal immune system, oxidative stress and colonocyte metabolism. - it reduces intestinal inflammatory processes with inhibition of the pro-inflammatory interleukin 8.
  • [1.1] [#Atopic Dermatitis
    - children and infants suffering from AD, or prone to develop allergic sensitization later in childhood43, exhibit a gut microbiota characterized by a reduced capacity to produce SCFA, particularly butyrate.
  • [1.25
    - #Roseburia intestinalis specifically able to metabolize the indigestible glycans β-mannans found in #Nuts into butyrate
  • [1.3] [#Behcet’s Disease] [#Lactate
    - These results showed that the gut microbiota in BD patients was enriched with lactic acid-producing bacteria, #Sulfate-reducing bacteria, and some opportunistic pathogens but lacked #Butyric acid-producing bacteria and methanogenic bacteria. - In mice receiving BD feces, it was observed that the intestinal barrier was disrupted with low expression of tight-junction proteins, leading to LPS release into circulation. - enrichment of #Bilophila, Alistipes, and #Paraprevotella was observed in the BD-recipient group.
  • [#Behcet’s Disease] - a similar effect was observed by the administration of #Eubacterium rectale (a kind of butyrate-producing bacteria) in BD mice, which can upregulate NK1.1+ cells and reduce serum IL-17 levels and disease severity scores, sharing the partial mechanism of colchicine, which is used to treat BD patients.
  • [1.13] [#Parkinson’s Disease
    - lower fecal butyrate and reduced counts of genera #Roseburia, #Romboutsia, and #Prevotella are related to depressive symptoms in PD patients. - Decreased levels of bacterially produced butyrate are related to epigenetic changes in leucocytes and neurons from PD patients and to the severity of their depressive symptoms.
  • [1.12] [#Neuromyelitis optica] [#Short Chain Fatty Acid
    - lower faecal SCFA levels in these patients, and a negative correlation between #Acetate and butyrate levels and disease severity.
  • - butyrate treatment of epithelial cells has been shown to increase the production of IL-18 by GPR109a
  • - #Propionate and butyrate regulate gene expression by directly inhibiting histone deacetylases (HDACs)
  • [#Colorectal cancer] - butyrate treatment of epithelial cells boosted IL-18 production via a GPR109a-mediated pathway, promoting stomach homeostasis and defending against colorectal carcinogenesis
  • [#Short Chain Fatty Acid] - SCFA levels were observed to be decreased in non-obese #Non-alcoholic fatty liver disease. - SCFAs help to inhibit the progress of NAFLD in a variety of ways. - As histone deacetylase inhibitors, #Propionate, #Acetate, and butyrate play an important role in NAFLD by decreasing chromatin-bound acetyl groups
  • [#Steatohepatitis] - #Acetate, #Propionate, and butyrate have been shown to alleviate hepatic steatosis by activating AMP-activated protein kinase, expressing a fatty-acid oxidation gene, and inhibiting macrophage proinflammatory activation
  • [1.16] [#Food Allergy
    - butyrate-producing #Clostridia, are depleted in food-allergic individuals. - butyrate-containing micelles, used in combination, restore a barrier-protective response in mice treated with either dextran sodium sulfate or antibiotics. Treatment with the micelles protects peanut-allergic mice from an anaphylactic reaction to peanut challenge and rescues their dysbiosis by increasing the abundance of #Clostridium cluster XIVa.
  • [1.21] [#Atopic Dermatitis
    - Supplement #Lactobacillus rhamnosus > increase butyrate production > reduce atopic symptoms
  • [1.35] [#Irritable bowel syndrome
    - a recent meta-analysis identified low levels of #Propionate and butyrate in feces from patients with IBS-C, as compared with healthy controls, and a higher proportion of butyrate in fecal samples of patients with IBS-D, as compared with controls
  • [#Irritable bowel syndrome] - #Lactobacillus paracasei CNCM I-1572 improves symptoms, modulates gut microbiota structure and function through the reduction of Rumicococcus with consequent increased levels of #Acetate and butyrate, and reduces intestinal immune activation in patients with IBS
  • [1.9] [#Antibiotic Therapy
    - In case of antibiotics treatment it decreases the production of SCFA like butyrate, #Propionate and #Acetate which increases inflammation.
  • [#Colorectal cancer] - Butyrate, on the other hand, induces apoptosis in malignant epithelial cells that line the large intestine, lowering the risk of bowel cancer while also providing energy to gut cells.
  • - Genera which produce Butyrate were almost absent in #Colorectal cancer patient’s stool.
  • [1.63] [#Multiple Sclerosis
    - concentrations of fecal SCFAs (i.e., #Acetate, butyrate and #Propionate) were decreased in RRMS patients, compared to healthy controls
  • [1.14] [#Almond
    - There were no significant differences in abundance of fecal bifidobacteria following consumption of whole almonds, ground almonds or control . - Consumption of almonds (whole and ground pooled) resulted in higher butyrate (24.1 μmol/g) in comparison to control (18.2 μmol/g. - There was no effect of almonds on gut microbiota at the phylum level or diversity, gut transit time, stool consistency or gut symptoms.
  • [1.15
    - #Almond consumption increased the relative abundances of Lachnospira, Roseburia, and Dialister. - chopped almonds increased Lachnospira, Roseburia, and Oscillospira. - while whole almonds increased Dialister compared to control. - microbial fermentation of finely ground almonds has been shown to increase butyrate concentrations
  • [1.64
    - The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in the gut. - oral exposure to #Graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish, with significant differences in wild-type versus ahr2-deficient animals. - GO was found to elicit AhR-dependent induction of cyp1a and homing of lck+ cells to the gut in germ-free zebrafish larvae when combined with the short-chain fatty acid butyrate.
  • [1.65] [#Sarcopenia
    - The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium—known butyrate producers—were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. - Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired.
  • [1.66] [#Consumption of Inulin-Type Fructans (ITF)
    - Butyrate production may also be driven by bacteria unable to degrade inulin type fructans, but are capable of consuming #Acetate, producing butyrate, and utilising partially degraded carbohydrate from #Bifidobacteria.
  • [#Consuming resistant potato starch, #Culinary herbs and spices] - #Eubacterium hallii, a lactate utiliser and butyrate producing strain of bacteria grows poorly on potato starch in monoculture, but when combined with #Bifidobacterium adolescentis in coculture, it can utilise lactate produced by B. adolescentis for butyrate production.
  • - increase in butyrate producing microbes with #Turmeric.
  • [1.17] [#Gastric bypass surgery
    - Higher butyrate- and #Propionate-to-#Acetate ratios after the surgery compared to baseline indicates a shift in microbial metabolism from #Acetate production to butyrate and #Propionate production. - butyrate and #Propionate, which are known to induce satiety in animals and humans, were in greater concentrations in post-RYGB patients compared to nonsurgical controls.
  • - #Lactate availability is crucial for butyrate producers and, therefore, colon epithelium health
  • [1.67] [#Diabetes Type 2] [#Coprococcus etes
    - There are 36 different strains of butyrate-producing bacteria, and five of them are associated with increased insulin sensitivity: #Coprococcus etes, #Oscillibacter sp. CAG 241, #Alistipes finegoldi and #Faecalibacterium prausnitzii. - The genus #Coprococcus was associated with higher insulin sensitivity and disposition index and a lower rate of dysglycemia.
  • - patients with #Prediabetes had significantly lower levels of butyrate bacteria than healthy people.
  • [1.68
    - n-butyrate protects against #Endometriosis disease progression in mouse model of this disease
  • [1.69
    - 5 weeks of #Exercise training in mice resulted in Gut Microbiota composition changes and an increase in cecal butyrate.
  • - Administration of butyrate promote NREM #Sleep in rats and mice. - #Sleep disruption can lead to changes in Gut Microbiota composition > tissue inflammation and decreased insulin sensitivity.
  • - #Ruminococcaceae (order Clostridiales) that are prominent producers of butyrate, decreased in relative abundance with a #High-fat diet. - This decrease is particularly significant because #Ruminococcaceae, making up ≈20% of gut bacteria in chow-fed OSA rats, decreased to ≈10% in high-fat OSA rats . Members of the order Clostridiales, other than #Ruminococcaceae, also significantly decreased with #High-fat diet.

Common References