Short Chain Fatty Acid {60000042} Record Keys Parent:[ ] Definition:Short Chain Fatty Acid Queue:[ ] Details Initialisation date:2020-09-17 Specification: SCFASource: [ ] LinksInfolink Meta Information Structural Type:Fatty acid Functional Type:Energy Source Function:Immun regulator, Anti-inflammatory, Anti-bacterial, Anti-cancer, Antioxidant, Anti-psychotic, Neurodevelopment, Energy source, Enhancing Gut integrity Notes: - About 90% of the total microbial number in adult gut belong to the two most abundant phyla, Bacteroidetes and Firmicutes, which together with Actinobacteria and Verrucomicrobia are the main producers of short chain fatty acids (SCFAs) generated by anaerobic fermentation from dietary carbohydrates (i.e. fiber) and amino acids (i.e. L-glutamate, L-lysine) (1) - SCFAs are the primary energy source for colonocytes and maintain intestinal homeostasis through its anti-inflammatory activities (1) - At the cellular level, SCFAs can influence the proliferation and differentiation of colonic regulatory T-cells (Treg) cells, as well as alter their gene expression (1) - SCFAs > stimulating mucus production by epithelial cells and the rearrangement of tight junction proteins > Maintaining intestinal barrier(1) -SCFAs > proliferation and differentiation of regulatory T cells (Tregs) and anti-inflammatory IL-10 secreted from Foxp3+ Tregs, which are mediated through GPR43 (also known as Ffar2) activation and HDAC inhibition (2) - SCFAs > promote mucus and antimicrobial peptides production > maintain intestinal barrier integrity and robust immunity. - SCFA-producing bacteria > direct effects of SCFA on vasodilation or through plasminogen activator inhibitor-1> blood pressure regulation (3)Shared Reference Notes [1.1] [1.2] - A lack of SCFAs-producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased #Stroke severity. The SCFAs levels were negatively correlated with #Stroke severity and prognosis. [1.3] - Protection against CKD trans-membrane G protein-coupled receptor activation [1.4] - SCFAs improve stroke recovery, in part, through effects on T cells. - Stroke led to a reduction in circulating SCFAs. [1.5] - Specialized cells such as enteroendocrine and enterochromaffin cells in the gut, which can sense many of the metabolites such as short-chain fatty acids produced by the gut microbiota from ingested dietary fiber (better referred to as Microbiota Accessible Carbohydrates, or MACs. send signals to the brain either via the bloodstream or via vagal afferent pathways. [1.6] - SCFAs and butyrate, in particular, has been established as playing a critical role in host metabolism (Kasubuchi et al., 2015) and intestinal anti-inflammatory action through NF-kB inhibition in colonic epithelial cells and regulatory T cell (Treg) and T helper cell 17 (Th17) response [1.7] [#Autism] - The reduction of #Bifidobacterium also results in reduced levels of short-chain fatty acids (SCFAs), common in ASD children. [1.8] - The blood–brain barrier allows the access of SCFAs. - Changes in KYN and SCFAs brain levels may underlay the development of mood disorders and anxiety. [1.9] - Propionate, acetate, and butyrate are the three most predominant SCFAs and are well-known modulators for cell invasion and apoptosis in #Breast cancer. - Decreases in the bacterially fermented metabolites of glycans, SCFAs, have been associated with IgE-mediated food #Allergy, providing an example of how dietary-driven microbiota changes can influence human health and disease [#High fibre diet] - Fiber-rich diets > maintain a healthy, diverse microbiome > beneficial metabolites such as short-chain fatty acids (SCFAs) > promote mucus and antimicrobial peptides production > maintain intestinal barrier integrity > robust immunity. [1.11] [#Diabetes Type 2] - Four G-protein coupled receptors (GPCRs) for SCFAs have been identified: GPR41 (free fatty acid receptor 3), GPR43 (free fatty acid receptor 2), GPR109a, and olfactory receptor 78. - Of the 4 receptors, the 2 most directly implicated in T2DM are GPR41 and GPR43. - GPR41 recognizes all 3 SCFAs but is activated 10-fold less by acetate and is reported to be expressed in adipose tissue, the gut by intestinal L-cells, the nervous system, and the kidney. - GPR41 resulted in increased gut motility via reduced peptide YY (PYY) secretion, which resulted in decreased intestinal absorption of nutrients, implicating a role in food consumption. - GPR41 activation stimulate energy expenditure, thereby having a protective effect against T2DM onset. In the kidney, GPR41 seems to play a role in decreasing blood pressure, which could play a protective role againstT2DM-mediated kidney damage in later disease stages. - Treatment with SCFAs in both rodent models and humans improves T2DM phenotypes [#Hypertension] - Olf78 >The last receptor for SCFAs > observed in the olfactory bulb, enteroendocrine cells, the kidney, blood vessels, skeletal muscle, and heart. - Acetate and propionate, but not butyrate > stimulate Olf78 > induces an increase in blood pressure via renin secretion . [1.12] [#Amyotrophic lateral sclerosis] - The fecal SCFA concentrations (µmol/g) were not significantly different between ALS patients and controls, or between patients with different clinical characteristics. [1.13] - #Parabacteroides > SCFA-producing > richer in the cecum and colorectum > more SCFAs were produced. [1.14] [#Iron-deficiency anaemia] - In iron-deficient rats, significantly lower concentrations of faecal butyrate and propionate were retrieved and the bacterial composition was strongly modified, involving a higher abundance of Lactobacilli and Enterobacteriaceae and a significant decrease of Roseburia species and Eubacterium rectale, which are major butyrate producers. In the same study, repletion of iron by the administration of FeSO4 led to increased caecal butyrate concentrations and partially restored microbial populations. - SCFA concentrations reach relative molar ratios for acetate-propionate-butyrate of approximately 60-20-20 respectively and for all human colonic regions. - Absolute concentrations are higher in the proximal colon due to the higher availability of carbohydrates and SCFA uptake by the epithelium. - Most SCFA are absorbed in the proximal colon in exchange for bicarbonate, which neutralizes the luminal pH. As a result, the pH in the cecum is lower than the rectum. - After absorption, the proportion of butyrate decreases to 8% in the portal blood and the propionate proportion to 12%. Eventually, this drop was thought to show that the metabolism of propionate and butyrate is mainly restricted to the intestinal mucosa [1.15] - A lack of SCFAs-producing bacteria and a low fecal SCFAs level defined dysbiosis in AIS patients, especially those with increased #Stroke severity. -The SCFAs levels were negatively correlated with #Stroke severity and prognosis. [1.16] [#Diabetic nephropathy] - SCFA receptors are expressed in the kidneys, and emerging data have demonstrated that intestinal dysbiosis activates the renal renin-angiotensin system, which contributes to the development of DKD. [1.17] [#Obesity] - SCFAs > activation of their receptors GPR43 and GPR41 > inhibits lipolysis > adipocyte differentiation. [1.18] [#Plant-based diet] - Plant foods and fish > positively associated with short-chain fatty acid-producing commensals and pathways of nutrient metabolism. [1.19] - SCFAs > inhibition of histone deacetylases (HDAC) > epigenetic control of gene expression - SCFAs >acting as ligands of G-protein coupled receptors -GPR43 and GPR41 (free fatty acid receptors 2 (FFAR2) and FFAR3) and GPR109A, also known as niacin receptor 1 or Hydroxycarboxylic Acid Receptor 2 (HCA2)- and by acting as an AhR agonist. - SCFAs > stimulate the production of the anorexigenic gut hormones peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) > improve insulin sensitivity and lean mass. [#Exercise training] - SCFAs > can be oxidized > incorporated into glucose via gluconeogenesis, or increase the bioavailability of glucose, glycogen, and fatty acids during exercise. - SCFAs > increased blood flow, insulin sensitivity, skeletal muscle mass preservation, and an oxidative phenotype [1.21] [#Colorectal cancer] - SCFAs > maintaining the integrity of the intestinal barrier to reduce the risk of colon cancer [#Parkinson’s Disease] - The onset age of PD is directly proportional to the SCFA level, suggesting that SCFAs may have a protective effect on PD - SCFAs > directly affect the sympathetic system > thereby increasing the release of mucosal #Serotonin and affecting learning and memory functions [1.22] - #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. [1.23] [#Monozygotic Twin Pairs] [1.24] [#Infectious diarrhea] - A drastic disappearance of obligate anaerobic gut commensals (#Blautia, #Prevotella, #Faecalibacterium, #Lachnospiraceae, #Ruminococcaceae, etc.), leading to a depletion of associated metabolites such as short chain fatty acid (SCFAs) [1.25] [#Parkinson’s Disease] [#Butyrate, #Indole-3-propionic 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. [1.26] - Short-chain fatty acids, especially butyrate and acetate, exhibit important anti-inflammatory effects, reduce oxidative stress, regulate gene expression, and maintain the integrity of the gut epithelial barrier. [1.27] - reduced levels of SCFAs were observed in patients with #Alzheimer’s disease, and they also promoted #Depression-like behaviors and impairments of short-term memory in mice [#Diabetes Type 2] - SCFAs-induced improvements in adipose tissue metabolism can prevent insulin resistance, while #Succinate improves the host insulin sensitivity while preventing obesity. - SCFAs, #Serotonin, #kynurenine, #Indole and its derivatives, and #Tryptamine, can bridge the gut and nervous system. [#Inflamatory bowel disease] - inflammatory bowel disease (IBD), SCFAs have been shown to alleviate inflammatory phenotypes by regulating IL-10 production by T cells in both humans and the mouse model. [#Metabolic associated fatty liver disease] - SCFAs are considered to be able to alleviate the development of nonalcoholic fatty liver diseases (NAFLD), which may derive from their potential contribution to regulating fatty acid oxidation, inflammation, and insulin resistance. - SCFAs can restore the function of the blood-brain barrier in patients with #Multiple Sclerosis. [#Obesity] - SCFAs have been reported to have potential to enhance intestinal gluconeogenesis, with hepatic glucose production declining and energy-spending increasing.2 Furthermore, SCFAs are capable of facilitating peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) secretion, which can promote satiety and increase peripheral glucose catabolism [#Respiratory tract infection] - In patients with respiratory inflammation, SCFAs downregulate IL-8 expression by targeting the activation of free fatty acid receptors 2 and 3 (FFAR2 and FFAR3) on macrophages and neutrophils, thereby reducing inflammation. - SCFAs have been confirmed to display antibacterial activity by disturbing the intracellular acid-alkaline balance or acylating certain virulence factors of #Salmonella typhimurium - SCFAs had the potential to alleviate chronic stress-induced insomnia and enhanced stress response, as well as stress-induced increases in intestinal permeability in mouse models. - SCFAs can promote microglia maturation and restore microglia defects. - SCFAs could also promote the production of antimicrobial peptides in the intestinal epithelium, thus helping the host to resist broad-spectrum pathogenic infections. - SCFAs could promote recovery after #Stroke by acting on microglia to inhibit their activation [1.28] - SCFA can elicit their immunomodulatory capacity by acting as histone deacetylase (HDAC) inhibitors, binding to specific receptors (principally FFAR2 and FFAR3), or influencing cellular metabolism. [1.29] - Recent meta-analysis reported a relatively inconspicuous alpha-diversity (as a measure of species diversity) of the gut microbiota, but altered beta-diversity (as a measure of the composition of species relative to one another), particularly less abundance of SCFA-producing bacteria in major mental disorders. [#Long-term daily high-protein yoghurt] - At day 42, total SCFA were significantly lower in the Skyr group compared to the Control with a trend of lower concentrations of #Acetate and #Propionate there was no significant difference at day 112. - The proportion of butyrate/total SCFA was significantly higher in Skyr compared to the Control group at day 42 [1.31] [#Neuromyelitis optica] - lower faecal SCFA levels in these patients, and a negative correlation between #Acetate and #Butyrate levels and disease severity. - SCFAs influence blood-brain barrier permeability through modulation of the expression of tight junction proteins. - SCFAs have extensively been shown to influence the numbers and maturation of microglia, the tissue macrophages of the CNS. [1.32] [#Diabetes Type 2] - SCFA-associated GPR43 (G-coupled receptor 43) has also been shown to suppress insulin signaling activity, decrease fat accumulation in adipose tissue, and improve energy homeostasis balancing [#Metabolic associated fatty liver disease] - 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 - Injection of SCFAs has been shown to enhance #Retinoic acid (RA) in intentional epithelial cells. - binding of SCFAs to GPR41 and GPR43 increased the production of antimicrobial factors such as RegIIIγ and β-defensins in IEC via increased mTOR and STAT3 signaling. - The regulation of antimicrobial molecules in epithelial cells could lead to an increase in metabolic signaling information. Acetyl-CoA regulates genes for plasma-cell differentiation and IgA antibody development. - #Staphylococcus epidermidis, and molecular mechanisms are activated by SCFAs via the liver feedback mechanism [1.33] [#Diabetes Type 2] [#Akkermansia muciniphila] [#Secondary bile acids] [#Oral administration of Metformin] - oral metformin has been shown to alter gut microbiome composition in obese adults with T2D, which was associated with secondary BA and FXR changes, resulting in improved insulin sensitivity - Metformin promotes colonization by SCFA-producing bacteria such as Akkermansia, Several studies of different ethnic populations with T2D and healthy individuals have demonstrated that metformin alters gut microbiome composition and is associated with changes in SCFA, BA, and C-peptide levels. [#Obesity] - SCFAs activate mucosal G protein-coupled receptors in the gut so they contribute to the regulation of secretion of incretin hormones such as glucagon like peptide-1, peptide YY and leptin. [1.34] [#Alzheimer’s disease, #Multiple Sclerosis, #Parkinson’s Disease] - SCFAs maintain the healthy mitochondrial function and stimulate the maturation of microglia, which consequently suppresses the progression of Neuro-Degenerative Diseases and cognitive decline by regulating inflammation and oxidative stress. - SCFAs functions as a cofactor for the host’s mitochondrial enzymes. - The properties of SCFAs depend on the G-protein coupled receptors (GPCR), histone deacetylases (HDAC) & peroxisome proliferator-activated receptor gamma (PPARγ) and regulatory T cells (Tregs) activation. [1.35] [#Diabetes Type 2] - the functionalities of SCFAs towards body tissues are mainly involvin the SCFA-specific receptors free fatty acid receptor 2 (FFAR2) and free fatty acid receptor 3 (FFAR3). - Increased secretion of insulin after SCFAs treatments were reported in many studies, but contradicting evidence also exist in several other studies. [1.36] - #Acetate is the major SCFA that is produced to the tune of 65% in the colon resulting in significant drops in pH. Thus, it helps in the inhibition of various pathogenic microorganisms and indirectly aids in the absorption of minerals such as calcium, iron, and sodium Butyrate, - #Acetate provides energy to colonocytes, possesses anti-inflammatory properties, protects against colon cancer, and plays a key role in gut homeostasis as well as maintaining the integrity of epithelium,. [#Resistant starch] - RS fermentation in the lower GI tract produces different starch oligomers and SCFAs [1.37] - SCFAs and secondary #Bile Acids modulate gastric inflammation and immune system activation by reducing NF-κB activation, promoting the secretion of anti-inflammatory cytokines, AMPs, and IgA, and preserving the integrity of the gut barrier - the abundance of each SCFA depends on substrate availability, gut microbiota composition, and gastrointestinal transit time. - SCFAs exhibit several local effects, such as preserving the intestinal barrier integrity and pH reduction as their concentration increase from the distal ileum (6.5–7.5) to the proximal colon (5.5–7.5). - SCFAs promote the induction and expansion of intestinal regulatory T cells, DCs, and macrophages, exert an anti-carcinogenic and anti-oxidative effect in the intestine,and suppress pathogen-induced inflammation [1.38] - Acetic acid is used by muscles [1.39] [#Multiple Sclerosis] - Individual dietary fiber sources have distinct impacts on T cell subsets - The dietary fiber #Guar gum impairs Th1 polarization and alters migratory potential - #Guar gum elevates short-chain fatty acids but does not impact regulatory T cells - #Guar gum supplementation significantly delays autoimmune neuroinflammation [#Multiple Sclerosis] - Blood SCFAs were significantly decreased in long-term active progressive MS patients. [1.41] [#Limosilactobacillus (Lactobacillus) reuteri] [#High Fat Diet] - maternal high-fat diet (MHFD) in mice induces gut dysbiosis, social dysfunction, and underlying synaptic plasticity deficits in male offspring. - Post-weaning Limosilactobacillus reuteri treatment increases the abundance of short-chain fatty acid-producing taxa and rescues MHFD-descendant social deficits. [1.42] [#Diabetes Type 2] [#Exercise training, #Fecal Microbiota Transplantation] - exercise-induced alterations in the gut microbiota correlated closely with improvements in glucose homeostasis and insulin sensitivity. - The microbiome of responders exhibited an enhanced capacity for biosynthesis of short-chain fatty acids and catabolism of branched-chain amino acids, whereas those of non-responders were characterized by increased production of metabolically detrimental compounds. - Fecal microbial transplantation from responders, but not non-responders, mimicked the effects of exercise on alleviation of insulin resistance in obese mice. [1.43] - #Ginger root consumption could increase Bifidobacterium spp., enhance faecal SCFA production as well as invoke anti-#Obesity effects in obese mice [1.44] [#CVD] [#Probiotic, #Probiotic (Bifidobacter and Lactobacilus)] - Short-chain fatty acids and secondary #Bile Acids can decrease #Cholesterol levels by regulating #Cholesterol metabolism. - Microbial #Bile Salt hydrolases can increase #Cholesterol disposal rates by accelerating its conversion to #Bile Acids. - Probiotics from the genera Lactobacillus and Bifidobacterium are efficient reducers of #Cholesterol levels in clinical studies. - Several candidate next-generation probiotics, including #Akkermansia muciniphila, #Bacteroides spp., #Clostridium spp., #Christensenella minuta, Eubacterium spp., and #Faecalibacterium prausnitzii, have been shown to decrease #Cholesterol levels in human or animal studies. [1.45] [#Parkinson’s Disease] - PD > a dramatic ~2.5-fold reduction for several SCFA producing species, and as much as 5 to 7.5 fold reduction in #Roseburia species. [1.46] [#Inflamatory bowel disease] The first signs of aggravation of IBD are : - a loss of the main anti-inflammatory Short-Chain Fatty Acids (SCFAs) #Roseburia, #Eubacterium, #Subdoligranumum, #Ruminococcus - an increase in pro-inflammatory pathogens #Proteus, #Finegoldia - an increase of other minor SCFA producers such as #Ezakiella, #Anaerococcus, #Megasphaera, #Anaeroglobus, #Fenollaria. - Further aggravation of clinical signs is significantly linked to the subsequent loss of these minor SCFAs species and to an increase in other proinflammatory Proteobacteria such as Klebsiella, Pseudomonas, Salmonella, Acinetobacter, Hafnia and proinflammatory Firmicutes such as Staphylococcus, Enterococcus, Streptococcus. [1.47] [#Gestational diabetes mellitus (GDM), #Pregnancy] [#Branched-chain amino acids] In GDM: - Isobutyric, isovaleric, valeric, and hexanoic acids were significantly higher in the GDM. - #Isobutyric acid significantly correlated with urea and blood glucose at 1 and 2 hours after OGTT; fasting blood glucose, blood glucose at 2 hours after OGTT. - urea/creatinine ratio positively correlated with #Valeric acid. - blood glucose at 2 hours after OGTT positively correlated with #Caproic acid. - white blood cell count positively correlated with #Propionic acid. - Significantly elevated #Isobutyric acid and isovaleric acid in pregnant women with GDM may be associated with insulin resistance caused by BCFAs. [#Intrahepatic Cholestasis of Pregnancy (ICP), #Pregnancy] In the ICP - isobutyric acids levels were higher, while acetic, propionic, butyric, isovaleric, valeric, and hexanoic acids levels were significantly lower. - #Isobutyric acid and #Hexanoic acid showed significant correlations with each clinical indicator. - Hemoglobin, white blood cells count, albumin, gestational weeks at delivery, fetal birth weight, and BMI were positively correlated with #Hexanoic acid. - total BAs and ALT were negatively correlated with #Hexanoic acid - #Isobutyric acid showed the opposite trend with #Hexanoic acid. - #Valeric acid positively correlated with hemoglobin and negatively correlated with total BA and ALT. - #Caproic acid and #Isobutyric acid might be potential biomarkers [#Preeclamsia, #Pregnancy] in PE: - #Acetic acid, #Propionic acid, #Isobutyric acid, and valeric acids levels were significantly higher in the PE group. - the systolic blood pressure, diastolic blood pressure, urea/creatinine ratio, and total BA of pregnant women significantly positively correlated with #Acetic acid, #Propionic acid, #Isobutyric acid, and #Valeric acid. - urea positively correlated with #Acetic acid and #Isobutyric acid. - white blood cell count and gestational age negatively correlated with #Acetic acid, #Propionic acid, #Isobutyric acid, and #Valeric acid. - total cholesterol negatively correlated with #Propionic acid and #Isobutyric acid. - the percentage of neutrophils and fetal birth weight negatively correlated with #Isobutyric acid and #Valeric acid. - #Acetic acid and #Propionic acid have high diagnostic value for PE. [1.48] [#Alzheimer’s disease] [#ApoE4 allele] - #Amyloid-beta is a necessary factor in AD pathogenesis, its accumulation in and of itself is insufficient for neurodegeneration and cognitive decline. - pathological #Tau accumulation is closely linked with neurodegeneration and cognitive decline in AD and primary tauopathies. - apolipoprotein E (ApoE) isoforms, which strongly influence AD risk and regulate #Tau-mediated neurodegeneration, differentially affect the gut microbiota. - microbially produced short-chain fatty acids (SCFAs) are mediators of the neuroinflammation-neurodegeneration axis. - Supplementation of SCFAs to GF TE4 mice resulted in more reactive glial morphologies and gene expression as well as increased p-#Tau pathology. [1.49] [#Infants] - a higher percentage of #Propionate in relation to total SCFA composition was associated with longer uninterrupted human infant #Sleep - Exercise increased fecal SCFA concentrations in lean but not obese participants. - These effects were reversed after 6 weeks of ceasing #Exercise training suggesting that sustainment of exercise is necessary for long-term exercise-induced Gut Microbiota alterations. - The concentrations of these SCFAs in the colon are in the order of #Acetate > #Propionate > #Butyrate with molar ratios of approximately 60:20:20. - The total luminal SCFA concentrations in humans are 70–140 mmol/kg in the proximal colon, 20–70 mmol/kg in the distal colon, and 10–20 mmol/kg in the terminal ileum. - Approximately 95% of the produced SCFAs are absorbed by colonocytes, and the absorbed SCFAs contribute to 5%–15% of the caloric requirement for humans. - The presence of SCFAs is sensed by intestinal epithelial cells and immune cells by G-protein coupled receptors (GPRs), such as GPR41, GPR43, GPR109a, and Olf78. - SCFAs act as type I and II histone deacetylase (HDAC) inhibitors, with #Butyrate and #Propionate having higher HDAC-inhibiting activities compared to #Acetate. - The three major SCFAs promote the proliferation of normal crypt cells in the intestine of healthy individuals. - Triggering GPR43 and GPR41 dynamically regulates the gut barrier, inducing tight junction proteins at steady state but rapidly increasing the permeability during infection, perhaps, to facilitate acute immune responses. [#Colorectal cancer] - GPR triggering by SCFAs is an important mechanism to suppress CRC development. - activation of GPRs on intestinal epithelial cells by SCFAs promotes barrier functions and stimulates the production of interleukin (IL)-18 and secretion of anti-microbial peptides. [1.51] [#Diabetes Type 2] - In four other genera (#Fusicatenibacter, #Agathobacter, #Butyricicoccus, #Marvinbryantia), a decrease in the T2D group could also be detected. All genera produce short-chain fatty acids [1.52] [#Acetate, #Butyrate, #Propionate] - #Inulin and #Rice bran promoted the production of all three SCFA - Resistant #Maltodextrin and #Inulin produced the greatest increase in total SCFA levels followed by #Resistant starch and #Rice bran [1.53] [#Multiple Sclerosis] [#Bile Salt] - MS > the absence of AHR, changes the gut microenvironment composition to generate metabolites that impact T cell viability, such as bile salts and short chain fatty acids. [1.54] [#Dementia with Lewy bodies (DLB), #Parkinson’s Disease] - short-chain fatty acids-producing genera were decreased in DLB. - #Ruminococcus torques and #Collinsella were increased in DLB, which were not changed in PD. - high #Ruminococcus torques and high #Collinsella, which presumably increase intestinal permeability, as well as low #Bifidobacterium, which are also observed in #Alzheimer’s disease, were predictive of DLB. [1.55] [#Hepatectomy] [#Acetate] - Phospholipid biosynthesis, hepatocyte proliferation, liver regeneration and survival were rescued in gnotobiotic mice colonized with a minimal SCFA-producing microbial community. - SCFAs (acetat) induced the growth of murine hepatocyte organoids and hepatic SCD1 expression in mice. - SCD1 was required for proliferation of human hepatoma cells and was associated with liver regeneration in human patients. [#Acetate] [#Antibiotic Therapy] - Three days of antibiotic treatment induced persistent dysbiosis with significantly decreased beta-diversity and richness, but a massive increase of #Proteobacteria, accompanied by decreased colonic SCFAs (acetat). [1.56] [#Epigallocatechin gallate] - ECGC contribute significantly also to increase the number of SCFAs-producing bacteria, especially #Akkermansia, enhancing the colon barrier integrity and general anti-inflammatory effects. [1.57] - #Butyrate can also be synthesized by the gut microbiota from #Acetate and #Lactate, although the last is not considered a SCFAs - The concentration of SCFAs is higher in cecum and proximal colon, and their levels decrease toward the distal colon - SCFAs exert anti-inflammatory properties. They induce the production of IL-10, closely related to intestinal homeostasis. - SCFAs are associated with improved neuronal and cognitive function, BBB integrity and decreased neuroinflammation in the brain. [1.58] [#High Fat Diet] - HF diets affect the composition of the gut microbiota limiting SCFAs production. - It reduces the diversity of bacterial strains and the abundance of #Bacteroidetes, promoting the growth of #Firmicutes and #Proteobacteria. - Animal studies confirmed the rise in pro-inflammatory cytokines and plasma #Lipopolysaccharide (LPS), with consequent pro-inflammatory signalling induced by NF-kB. [1.59] - in #Centenarians, longevity is positively associated with an abundance of short-chain fatty acid (SCFA) producers, such as #Clostridium cluster XIVa, #Ruminococcaceae, #Akkermansia, and #Christensenellaceae [#Aging] - Age-related intestinal dysbiosis is generally characterized by a decrease in short-chain fatty acid producers, for example, #Clostridiales, and #Bifidobacterium, and enrichment of pro-inflammatory #Proteobacteria including the opportunistic #Enterobacteriaceae. - SCFA such as #Butyrate, and #Secondary bile acids, might influence mitochondrial functions related to energy production, mitochondrial biogenesis, redox balance and inflammatory cascades, increased SIRT1 and FIAF activity, higher carbohydrate and fatty acid metabolism [#Reactive Oxygen Species] [#Sport] - the gut microbiota and its metabolites, such as short chain fatty acids and #Secondary bile acids, also contribute to host energy production, ROS modulation and inflammation in the gut by attenuating TNFα- mediated immune responses and inflammasomes such as NLRP3. [1.61] [#humanized Galactooligosaccharides] [#Fructooligosaccharides] - prebiotics that promote SCFA production such as #Fructooligosaccharides (FOS), galactooligosaccharides (GOS) or #Inulin, have been shown to have multiple beneficial immune- and metabolic- effects that can ultimately improve cognition. - treatment with SCFAs could reverse the microglial immaturity and malformation observed in germ-free mice indicating the importance of microbial-derived metabolites in shaping the microglial responses [1.62] [#Klebsiella pneumoniae, #Limosilactobacillus (Lactobacillus) reuteri] - In the K. pneumoniae infection mice model, gut microbial composition (down-regulates Lactobacillus reuteri and #Bifidobacterium pseudolongum) and cecal metabolome (SCFAs) are altered [1.63] - hemorrhagic transformation (HT), a life-threatening #Stroke complication in MCAO rats, correlated with inflammatory response and serum levels of SCFA. - total SCFA, specifically #Butyrate and #Valeric acid, was significantly lower in HT rats than in non-HT rats. - ischemic #Stroke can be effectively treated by transplanting SCFA-rich feces and supplementing it with #Butyric acid. - SCFA can promote post-#Stroke recovery by altering the recruitment of brain-resident immune cells in the brain. [1.64] [#Irritable bowel syndrome] [#Propionic acid] - the concentration difference in two SCFAs, propionic minus #Butyric acid, has been shown to be positive for all four IBS subtypes but negative in healthy subjects - Several receptors have been identified for SCFAs such as free fatty acid receptor 3 (FFAR3 or GPR41) and #Niacin receptor 1 (GPR109A) - GPR41 and GPR109A are G-protein coupled receptors (GPCRs) found on intestinal epithelial cells, immune cells, and adipocytes. - GPR41 is associated with increased energy expenditure, #Leptin hormone expression, and decreased food intake [1.65] - The supplementation of SCFAs reduced inflamm-#Aging, #Oxidative stress, metabolic alteration, and enhanced activation of myeloid cells in the lungs of old mice. [1.66] - SCFAs modulate signaling pathways through activation of free fatty acid receptors, increasing secretion of #Leptin, glucagon-like peptide-1 (#GLP-1), and peptide YY (PYY), leading to increased satiety and reduced energy intake. [#Obesity] [#Pancreatic polypeptide YY] - SCFAs act as signalling molecules, activating the free fatty acid receptors, increasing #Leptin, GLP-1, and PYY, promoting satiety. -SCFAs elicit mitochondrial fatty acid β-oxidation, favouring energy expenditure. [1.67] [#Colon adenomas] - Microbial species that were abundant in people with serrated adenomas included short-chain fatty-acid-producing microbes such as #Ruminococcus lactaris, #Eubacterium ventriosum, #Odoribacter splanchnicus, #Anaerostipes hadrus and #Alistipes shahii. - serrated adenomas tend to associate with multiple microbial antioxidant defense systems. [1.68] [#Olive] - SCFAs, produced by a number of bacteria, such as #Bacteroides and #Lactobacillus, which are often elevated with EVOO consumption, are also potent activators for GPR43 [#Diabetes Type 2] [#Glucose] - SCFA #Acetate activates GPR43, promoting GLP-1 release from colonic L cells. [1.69] [#Western-style diet] - The lower 16S rRNA gene copy number on the WD suggests a decrease in microbial biomass due in part to lower fermentable substrate availability to the microbes from the diet. - Lower fecal and serum SCFAs on the WD point to lower microbial fermentation, which is an indicator of reduced microbial energy harvest. - the increased relative abundance of mucin degraders on the WD suggests that the microbiota was “starved” of diet-derived substrates and turned to the host-derived energy sources such as mucin. [#Exercise training] - A six-week moderate to intense aerobic exercise (30–60 min) program can induce a shift in the SCFA-producing #Faecalibacterium and #Lachnospira spp. and genetic machinery (BCoATe) substantially in lean versus obese participants. - SCFA supplementation for four weeks can reinforce #Muscle strength to levels similar to those in mice with gut microbiota. [#Exercise training] - SCFAs, in response to aerobic exercise, can decrease the luminal pH (colon) by decreasing the conversion of #Primary bile acids to #Secondary bile acids and promoting colonic acidification. - The environment created as a result of these changes is more favorable for the growth of healthy commensal bacteria [1.71] [#Cesarean section] - #Children born by C-section exhibit an overall reduced gut microbiome stability and reduced stool levels of SCFAs (especially #Acetate) during the first months of life as well as a delayed maturation of the gut microbiome by the second year of life. [#Antibiotic Therapy] - Intrapartum antibiotics exposure is associated with reduced relative abundance of #Bacteroides and reduced levels of the SCFA #Propionate at birth, as well as increased relative abundance of potentially pathogenic #Proteobacteria. [#Covid-19] [#Human adenovirus, #Human coronavirus] - Increased abundance of SCFA-producing bacteria appears to offer protection against many common respiratory viruses including #Rhinovirus, #Respiratory syncytial virus, adenovirus, #Influenza and severe acute respiratory syndrome #Coronavirus 2 (SARS-CoV-2) [#Western-style diet] - SCFA supplementation has also been shown to increase #Leptin sensitivity in mice fed a Western diet [#Low fibre Diet, #Maternal consumption of dietary fibre] - a low-fibre diet during #Pregnancy and lactation leads to reduced SCFA levels and impaired thymic Treg cell differentiation in the offspring - School-age #Children living in #Urban areas show reduced relative abundance of bacteria (for example, #Prevotella spp.) capable of fermenting complex carbohydrates for the production of SCFAs and reduced stool levels of all major SCFAs. [1.72] [#Lipopolysaccharide] - #Hypertension groups > low gut microbial diversity and some distinctive taxa, depleted SCFA-producing bacteria, such as Ruminococcacea and #Faecalibacterium, and enriched LPS-producing gram-negative bacteria, such as #Bacteroidales, #Negativiticus, and #Megamonas, [#Hypertension] - normotension group exhibited higher levels of Gram-positive bacteria, such as #Clostridia, #Ruminococcaceae, and #Lachnospiraceae, which are mostly SCFA-producing bacteria. [1.73] [#Alzheimer’s disease] - #Methanobrevibacter smithii was associated with preclinical AD and was negatively correlated with fecal concentrations of #Butyrate, a SCFA that attenuated Aβ plaque deposition and neuroinflammation in a mouse model of AD. [#Alzheimer’s disease] - #Succinate is a major precursor for the short-chain fatty acid (SCFA) #Propionate, which has previously been found to be elevated in symptomatic individuals with AD, as well as in AD mouse models, compared with healthy controls. - The pathway most associated with healthy individuals (l-#Glutamate degradation V) produces the SCFA #Acetate, which not only has been observed to inhibit Aβ aggregation in vitro and protect against #Cognitive impairment in mice but also has been associated with an elevated Aβ SUVR in a human cohort [1.74] [#Butyric acid] - Administration of SCFAs, such as butyric, acetic, and #Propionic acid, has been reported to improve stress response, #Anxiety, and #Depression. [#Serotonin] - gut microbiota may promote the development of functional #Constipation through microbial metabolites, including #Bile Acids, SCFAs, 5-hydroxytryptamine, and #Methane. [#Diabetes Type 2] - The relation between SCFAs and insulin sensitivity stems from the capacity of SCFAs to stimulate the secretion of GLP-1 by intestinal L-cells via G protein receptors, which has a significant impact on insulin release. [#Indole-3-propionic acid] - #Fasting considerably increased plasma levels of indolepropionic acid and #Tauroursodeoxycholic acid and fecal levels of SCFAs. - SCFAs can regulate the pH value in the intestine and regulate the absorption of water, sodium, calcium, and #Magnesium. [1.75] [#Polysaccharide] - #Ruminococcaceae degrade several types of polysaccharides in the lower gastrointestinal tract and facilitate the production of protective short-chain fatty acids [1.76] [#Blood Brain Barrier Integrity] - Some SCFAs such as #Butyrate, #Propionate and #Acetate can cross the BBB probably through the monocarboxylate transport system generating a feedback inhibition on brain uptake. [1.77] [#Parkinson’s Disease] - depletion of SCFA-producing bacteria (e.g., #Lachnospira and #Butyricicoccus), has already occurred at prodromal PD (RBD and RBD-FDR). [1.78] - ignificant increases in the SCFA #Butyrate and several VOCs after #Almond consumption [1.79] [#Osteoporosis] - Gut microbiota modulates host IGF-1 levels through the production of SCFAs. - the serum level of IGF-1 has been correlated with the abundance of cecal SCFAs. T - IGF-1 binds the IGF receptor present in osteoblast/osteoclast resulting in stimulating bone [#Hypertension] - Blood pressure is a strong AF risk factor. - Bacteria of the genus #Odoribacter odproduce the SCFA acid #Butyrate, a signalling molecule in blood pressure control. - SCFAs interact with G-protein coupled receptor pathways including renin secretion and sympathetic activation,which are central to blood pressure regulation. [1.81] [#Bacteroides uniformis] [#Exercise training] - #Acetate and #Propionate are associated with increased B. uniformis abundance in the gut. - These SCFAs may facilitate muscle #Glucose supply from the liver during exercise. [#Bacteroides uniformis] [#Exercise training] - B. uniformis administration in mice increased swimming time to exhaustion, cecal short-chain fatty acid concentrations, and the gene expression of enzymes associated with gluconeogenesis in the liver while decreasing hepatic glycogen content. [1.82] - #Dry eye syndrom > Reduced SCFA has been found to alter the circadian rhythm, which in turn reduces lacrimal gland secretions. [1.83] [#Inflamatory bowel disease] - the genus #Allobaculum of the phylum Firmicutes was increased in the 5-ASA group compared with the NT group. Because #Allobaculum produces short-chain fatty acids (SCFAs) [1.84] [#Diabetes Type 2] - A few examples of SCFA-producing bacteria are #Blautia hydrogenotrophica and #Marvinbryantia formatexigens, #Veillonella spp., #Dialister spp etc. - Levels of SCFAs in T2DM patients are always lower than the healthy subjects. - The mechanism of action of SCFA includes promoting insulin secretion, improving insulin sensitivity, activating intestinal gluconeogenesis, increasing energy expenditure, reducing fat accumulation and inflammation. - They promote the production of satiety hormones and reduce the feeling of appetite. [1.85] [#Colorectal cancer] [#Zizyphus jujuba cv. Muzao] -ZMP consumption prevented CRC mouse colon shortening, decreased their mortality, reduced pro-inflammatory cytokines, increased the concentration of total short-chain fatty acids (SCFAs) and modulated gut microbiota in their feces. - ZMP also increased the richness of #Bifidobacterium, #Bacteroides and #Lactobacillus. [1.86] [#Polycystic ovary syndrome] [#Butyrate] - Butylated #Starch could be metabolized by the gut microbiota to produce SCFAs, which could stimulate the peptide-#Tyrosine-#Tyrosine secretion and the hypothalamic-pituitary-ovarian axis to alleviate PCOS. [1.87] [#Infants] - bacterial #Pentose phosphate pathways > lead to the formation of metabolites with neuroactive properties that can modulate the brain, such as SCFA, and the nucleosides/nucleotides salvage, which is necessary to maintain the levels of nucleotides in times or rapid growth and development, among other pathways [1.88] [#Parkinson’s Disease] - Decreases of short-chain fatty acid-producing genera, #Fusicatenibacter, #Faecalibacterium, and #Blautia, as well as an increase of mucin-degrading genus #Akkermansia, predicted accelerated disease progression. [1.89] - Most #Acetate and #Propionate are absorbed into circulation, while #Butyrate is the primary energy source for intestinal epithelial cells. - SCFA-sensitive receptors are expressed in many cell types throughout the body, including immune cells, adipose tissue, cardiac tissue, skeletal muscle, and neurons. - SCFAs, particularly #Propionate and #Acetate, have the potential for broad action in the host, including metabolism, cell differentiation and proliferation, gene regulation, protein methylation, and phosphorylation. [#Hypertension] - SCFAs, produced by the fermentation of fiber by gut microbiota, may activate receptors in the kidneys and blood vessels to inhibit renin release and decrease blood pressure [#Pancreatic polypeptide YY] - SCFA production is associated with the synthesis and secretion of intestinal hormones, such as GLP-1 and PYY, which play a role in satiety, intestinal transit, and homeostasis - #Oat β-glucan has demonstrated potential #Prebiotic properties through its fermentation to SCFAs - increased abundance of gut ##Ruminococcus and ##Alistipes in castration-resistant #Prostate cancer (CRPC) patients along with ##Bacteroidales, ##Rikenellaceae, ##Faecalibacterium,the so called SCFAs-producing microbiotas. [#Prostate cancer] - FMT with CRPC patients’ fecal suspension > increase SCFAs-producing gut microbiotas such as #Ruminococcus, #Alistipes, Phascolarctobaterium in TRAMP, and correspondingly raised their gut SCFAs (#Acetate and ##Butyrate) levels. [#Prostate cancer] - SCFAs upregulated the expression of a majority of TLRs family, and TLR3-triggered autophagy promoted PCa cells migration and invasion. - TLR3 perceived SCFAs to induce PCa cells autophagy, and activate survival signalings like NF-κB and MAPK. [#Prostate cancer] - Gut microbiota-derived SCFAs under #High Fat Diet could promote PCa growth via IGF1 signalings. [1.91] - #Butyrate, #Propionate and physiologically relevant SCFA mix of #Acetate, #Butyrate and #Propionate did inhibit focal cytokine production by macrophages in the presence of PRR stimulation, but timing is important! - The SCFA anti-inflammatory effect was apparent if their addition occurred at the same time as PRR activation. - Pre-treatment of macrophages with SCFA at least 1 hour before PRR stimulation had a pro-inflammatory effect. - Modest (1 mM) concentrations of SCFAs were cytotoxic to macrophages over the course of a 24-hour stimulation - thus stimulation was restricted to 6 hours. Interestingly, this cytotoxicity could be rescued by PRR activation by some microbes. [1.92] - An additional function of SCFAs is to lower the colonic luminal pH to inhibit growth of pathogens such as #Salmonella and #Escherichia coli [1.93] [#Prostate cancer] - #Subdoligranulum, #Lachnobacterium, #Christensenellaceae, #Lachnospira, #Rikenellaceae, #Eggerthella, and #Alistipes are members of the SCFA-producing order #Clostridiales and were shown to be more prevalent in individuals with high-grade PCA. [#Prostate cancer] - PCA cells release IGF-1 in an autocrine manner, which promotes PCA development by activating the mitogen-activated protein kinases (MAPK) and phosphoinositide 3-kinases (PI3K) signaling pathways. - Through both systemic and local prostate IGF-1, SCFAs, a significant gut microbiota metabolite, control PCA development. [1.94] [#Major depressive disorder] - SCFAs were reported to be depleted in patients with MDD,2,32 while their administration resulted in antidepressant effects by ameliorating #Depression-related intestinal permeability and hypothalamic–pituitary–adrenal (HPA) axis reactivity, in particular #Butyrate [1.95] [#Hepatocellular cancer] - Probiotics also increase bacteria that produce SCFA, such as #Butyricimonas and #Prevotella, and prevent HBV and HCV infections, thereby reducing HCC progression [1.96] [#Christensenellaceae, #Prevotellaceae] - #Berberine > the relative abundances of #Parabacteroides, Prevotellaceae_UCG-001, and Prevotellaceae_NK3B31_group increased, the relative abundance of Christensenellaceae_R-7_group decreased, and cecal SCFA levels (#Acetic acid and #Propionic acid) were reduced. [1.97] - #Ruminiclostridium may be a beneficial component of the gut MB, as it is involved in secretion of short chain fatty acids (SCFAs) and plays a role in maintenance of intestinal epithelial cells [1.98] - The G protein-coupled receptor (GPCR) GPR43 is an SCFA receptor which has also been implicated in mouse models of #Atopic Dermatitis - Sodium #Butyrate is an SCFA which can act via GPCRs to inhibit histone deacetylase (HDAC), leading to reduced neuronal death and #Oxidative stress. - the inhibition of HDAC by sodium #Butyrate was also shown to improve hearing in guinea pigs previously impacted by the antibiotic gentamycin - higher abundance of #Coprococcus eutactus, a producer of the short-chain fatty acid #Butyrate, was associated with better language outcomes - In the brain, SCFAs have been shown to regulate microglial development and activity in mice [1.99] [#Lactobacillus ruminis] - L. ruminis possesses genes contributing to the #Pentose phosphate pathway, which contributes to SCFA production. - SCFAs decrease the pH of colon. - SCFAs, the products of #Prebiotic fermentation, could induce the expression of #Tyrosine hydroxylase [1.101] [#Anaerostipes hadrus, #Blautia wexlerae, #Eubacterium hallii, #Fusicatenibacter saccharivorans] - The depleted bacterial populations are known short-chain fatty acid (SCFA) producers, notably the #Butyrate producers A. hadrus, E. hallii, and F. saccharivorans and the #Acetate producer B. wexlerae - depletion of #Butyrate in #Allergy-prone participants significant associations between A. hadrus and F. saccharivorans respective relative abundance and #Butyrate concentration. [1.102] [#Metabolic Dysfunction-associated Steatohepatitis] - #Alistipes, which are potential SCFA-producing bacteria that reduce hepatic fibrotic conditions through cytokine modulation, have been found at lower levels in the guts of NASH and NASH-#Cirrhosis patients - #Olsenella, an SCFA producer, is associated with tight junction improvement. [1.103] [#Lipopolysaccharide] - SCFAs, especially #Propionic acid, and #Butyric acid, can inhibit the expressions of cytokines #IL-6 and #IL-12 induced by LPS in human mature dendritic cells. - SCFAs trigger the generation of #Prostaglandin E2 and the #IL-10 levels by stimulating GPCRs, and can also activate inflammasomes, promoting the production and secretion of #IL-18. - SCFAs suppress histone acetylation, thereby inhibiting gene transcription [1.104] - accumulation of nonfermentable #Nitrate further inhibits the growth of short-chain fatty acid- (SCFA-) producing microbes, as they are unable to utilize this substrate. [#Ulcerative Colitis] - UC > depletion of SCFA-producing #Bacteria such as #Prevotella, #Roseburia, #Lachnospiraceae, and #Ruminococcaceae. [#Ulcerative Colitis] - A significant loss of SCFA-producing microbes and the concurrent increase in #Nitrate-reducing bacteria in UC patients favor a shift towards a proinflammatory microbiome > enrichment of #Lactic acid-producing bacteria is a consequence of increased inflammation. [1.105] [#Neuropathic Pain] - short-chain fatty acids (SCFA) and bile acids can indirectly decrease the excitability of dorsal root ganglion (DRG) neurons by releasing anti-inflammatory cytokines (i.e., interluekin-4, #IL-4) or neuropeptides (e.g., opioids) from immune cells to inhibit pain [1.106] [#Cutibacterium acnes, #Staphylococcus epidermidis] - some SCFAs produced by C. acnes are antimicrobial and can inhibit biofilm formation by other organisms such as S. epidermidis [#Cutibacterium acnes] - C. acnes produces high amounts of #Propionic acid and other SCFAs, which creates a lipid-rich environment that is favorable for the growth and proliferation of the bacteria. [#Cutibacterium acnes] - Production of SCFA including #Propionic acid promotes an acidic environment that influences the survival of skin microbiota, formation of biofilms, as well as the function of pH-dependent enzymes required for lipid synthesis - SCFA can also activate nuclear receptor PPARs. - PPAR agonists have been shown to increase epidermal lipids and induce an improved permeability barrier in mouse skin [1.107] [#Tuberculosis] - TB infection reduced the SCFA production in feces which included significantly low levels of #Butyric acid, #Isobutyric acid, #Valeric acid, and #2-metylbutic acid. However, the levels of #Propionic acid and #Acetic acid were non-significantly reduced and elevated, respectively, in the TB group compared with HC. [1.108] - a large number of gut bacteria consume #Uric acid anaerobically, converting it to either #Xanthine or #Lactate and the short chain fatty acids (SCFAs), #Acetate and #Butyrate. [1.109] - #Butyrate and other short-chain fatty acids (SCFA), which originate from the fermentation of dietary fibers by the microbiota, can activate #AHR signaling in reporter cell lines - only 2% of #Butyrate enters systemic circulation, being utilized by other tissues and cells. - The remaining SCFAs, including #Butyrate, are excreted through the lungs and urine. - Combination of SCFAs, mainly #Acetate, #Propionate, and #Butyrate, showed increased effects against #Colitis [1.111] - The microbiome-derived metabolites such as short-chain fatty acids (SCFAs), e.g., #Acetate, #Propionate, and #Butyrate are the commonly identified signaling metabolites that affect microglia. [1.112] [#Parkinson’s Disease] [#Roseomonas mucosa] - #Constipation severity is significantly correlated with the decrease of #Blautia and #Faecalibacterium, short chain fatty acids (SCFAs)-producing taxa that can exert positive effects on the intestinal mucosa and which are decreased in PD. [#Parkinson’s Disease] - SCFAs can promote gastrointestinal motility and regulate the function of the enteric nervous system, which is why a reduction of SCFAs might contribute to the development of gastrointestinal motility disorders such as #Constipation in PD [#Parkinson’s Disease] - PD > low SCFAs are significantly associated with poor cognition and low BMI; lower #Butyrate levels correlate with worse postural instability-gait disorder scores [#Parkinson’s Disease] - SCFAs were recently reported to have protective properties against #Dopamine and #Tyrosine hydroxylase depletion in the substantia nigra [#Parkinson’s Disease] - A reduction of SCFAs-producing bacteria leading to SCFAs deficiency may result in detrimental effects in PD patients, including gut leakiness, increased colonic inflammation, increased risk of α-synuclein deposition in the gastrointestinal tract, and microglial activation in the brain [1.113] - #Kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (#Butyrate), and in the brain (#Butyrate and #Propionate). [1.114] [#Colorectal cancer] - direct stimulation of CRC cells with SCFAs upregulates their ability to activate cytotoxic CD8+ T cells but the magnitude of this effect differs according to the CRC subtype and is strongest in those with deficient DNA repair. - the main mechanism by which SCFAs initiate improved antitumor immunity in CRC cells is via their function as HDAC inhibitors. Decondensing chromosomes is known to change susceptibility of DNA to potentially damaging agents and to alter the efficacy of DNA repair at the newly exposed sites. - CRCs exhibiting microsatellite instability (MSI) due to inactivation of DNA mismatch repair were much more sensitive to SCFAs and induced much greater CD8+ T cell activation than chromosomally instable (CIN) CRCs with intact DNA repair, indicating a subtype-dependent response to SCFAs. [1.115] [#Atopic Dermatitis] [#Clostridioides difficile] - gut microbiome structure in patients with AD > increased abundance of Clostridium difficile and decreased abundance of short-chain fatty acid (SCFA)-producing bacteria such as #Bifidobacterium. [1.116] - gut microbiota regulated metabolites, such as SCFAs, modulate #GLP-1 levels, either as energy substrates4 or as FFAR2/3 agonists. [1.117] [#Colorectal cancer] [#Fusobacterium nucleatum] - F. nucleatum-derived short-chain fatty acid #Formate > CRC cell stemness and invasion [1.118] - SCFAs trigger autophagy in #Cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. - By preventing cell proliferation and migration, lowering HDAC, and triggering apoptosis, SCFAs in the host gut and other areas might significantly reduce carcinogenesis, which would be beneficial for both preventing and treating malignancies of the gastrointestinal tract and the lungs - SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. [1.119] [#High fibre diet] - dietary fibre supplementation (for any type of dietary fibre) on levels of faecal or serum SCFAs > Only 38% of the randomised controlled trials reported significant increases in one or more SCFAs, while 62% did not. - increased production of SCFAs by gut microbes in humans might occur only with certain types of fibre [#Preeclamsia] - In the late trimester, the relative abundance of #Anaerovibrio was significantly decreased in PE patients, which is a short-chain fatty acid (SCFA) #Butyrate-producing bacteria. [1.121] - modulatory effects of SCFAs (primarily #Butyrate) on mitochondrial metabolism have been reported in macrophages, B cells, and innate lymphoid cells [1.122] - short-chain fatty acids (SCFAs) > modulate mucosal immunity in the intestine; by sending a signal through guanine nucleotide-binding proteins (G-protein) coupled receptors, SCFAs stimulate enterocyte production of #IL-18 and they act directly on the Treg, regulating its size and role [1.123] - #Butyrate administration might also have a long-term positive effect since it is able to reshape the gut microbiota composition and progressively boost and replenish SCFAs bacteria [#Chronic kidney disease] - fecal and serum SCFAs are remarkably higher in healthy controls than in patients affected by CKD. - the progression of CKD negatively correlates with the amount of #Butyrate detected in the serum of the patients. - #Butyrate supplementation might have potential beneficial effects on kidney function [1.124] [#Alzheimer’s disease] - The parabiont #Desulfovibrio has also been found to be enriched in other Alzheimer’s cohorts and is associated with reduced caecal levels of SCFAs and with inflammation in mice. [1.125] [#Hypertension] - The increased abundance of #Alloprevotella in the hypertensive mice was in line with a previous report that the SCFAs have higher levels in the feces of hypertensive individuals [1.126] [#Autism] [#Caproic acid, #Isobutyric acid, #Isovaleric acid, #Propionic acid, #Valeric acid] - higher levels of propionic and valeric acids as well as the sum of minor SCFA (isobutyric + isovaleric + valeric + caproic acids) were found in ASD at the age 4–7 years, but these differences disappeared at the age of 8–10 year [#Autism] - #Coriobacteriaceae, microorganisms significantly increased in the ASD group, correlated positively with all SCFA [1.127] [#Autism] [#Butanoic acid, #Propanoic acid] - a bi-directional perturbation of the dopaminergic pathways by both propanoic and butanoic acids has been described, suggesting that a similar dysregulation of brain catecholaminergic system occurs, as a response, in the presence of excessive concentrations of SCFA [#Autism] - #Propanoic acid was associated with the CBCL_EXT scale for ASDs with risk of symptoms, compared to ASDs without clinical symptoms, hence suggesting a role for SCFAs in the manifestation of behavioral problems. [#Butanoic acid] - SCFAs, particularly butanoic and #Acetic acid, can be produced by #Faecalibacterium, #Roseburia, #Sutterella, and #Prevotella - SCFAs do not act as a neuroactive substances class, but they play a pivotal role in preserving #Neurotransmitters [1.128] [#Bacteroides ovatus, #Bacteroides uniformis, #Bacteroides vulgatus] - the size of the left nucleus accumbens were dominated by Bacteroides species, especially B. vulgatus, B. uniformis, and B. ovatus. B. ovatus has been shown to produce a number of neuroactive compounds including SCFAs and #Neurotransmitters such as γ-aminobutyric acid (#GABA) [1.129] [#Blood Brain Barrier Integrity] - SCFAs can cross the BBB and activate (#Propionate) or inhibit microglia in addition to favoring the inflammatory process. - alterations in the #Glutamate-#Glutamine-#GABA cycle and increased SCFAs have been observed in patients with #Schizophrenia. - genera #Lactobacillus and #Megasphaera are increased in #Schizophrenia (SZ), as well as alterations in the #Glutamate-#Glutamine-#GABA cycle, serum levels of #Tryptophan, #kynurenic acid (KYNA), and short-chain fatty acids (SCFAs). - increased levels of total SCFAs and #Butyrate in mice that had received the #Beta-glucan intervention. [1.131] [#Covid-19] [#Roseomonas mucosa] [#mRNA vaccine] - different bacterial groups from #Lachnospiraceae to be associated with either high or low spike IgG levels. - bacterial members belonging to the family #Lachnospiraceae are well-known producers of SCFAs in colon mucosa-associated microbiota. - #Lachnospiracea FSC020, which shows a positive association with spike IgG levels > a potential positive association with the production of #Acetate and propionat [#Covid-19] [#mRNA vaccine] - #Marvinbryantia was observed to be less abundant in the younger group. - enrichment of #Marvinbryantia spp., which are SCFA-producers, in the elderly > a lower response to vaccinations, [1.132] - Hexane is commonly used for the extraction of less polar SCFAs, such as #Caproic acid and caprylic acid. - Fecal samples are a conventional choice for evaluating SCFA production within the gastrointestinal tract > may not accurately reflect the local rates and levels of SCFA production > because as much as 90 % of these metabolites are absorbed by colonocytes. - The concentration of SCFAs varies along the length of the gut. - The highest levels are typically found in the cecum and proximal colon, gradually decreasing towards the distal colon. - Plasma samples are useful for evaluating systemic SCFA, despite their typically low concentrations. - SCFAs produced in the gut can be transported via the portal vein to the liver, where they undergo metabolism before being released into the systemic circulation. - Adipose tissue is a significant site for SCFA uptake and metabolism, while the brain can also use SCFAs as an energy source. - SCFAs are volatile compounds that can evaporate during sample preparation and analysis. [1.133] - #Electro-acupuncture treatment effectively ameliorated both pain and #Depression-like behaviors. - Electro-acupunctureprofoundly reshaped the gut microbiota composition, notably increasing the abundance of SCFAs-producing bacteria, particularly #Akkermansia. - #Electro-acupuncture treatment > alterations of #BDNF, HDAC2, and AcH3 [1.134] [#Metabolic syndrome] - #Butyrate is the only SCFA that can bind to GPCR109a and regulate body energy expenditure to maintain metabolic homeostasis. [1.135] - #Butyrate (one of SCFAs) can regulate the differentiation of T lymphocytes in the intestinal tract and then play an anti-inflammatory effect [1.136] - SCFA-producing #Bacteria such as #Akkermansia, #Butyrivibrio, #Holdemania, #Anaerostipes, and #Intestinimonas were identified in this study as part of the gut microbiota associated with #Hypothyroidism. - SCFAs play a crucial role in the regulation of sodium/#Iodine symporter (NIS) expression in thyroid cells. - #Butyrivibrio to produce SCFAs and influence the intestinal environment may be a significant factor in #Hypothyroidism. [#Thyroid carcinoma] - SCFA, particularly #Butyric acid, inhibits histone deacetylase (HDAC) and activates NIS re-expression in thyroid cancer cells, leading to redifferentiation and enhanced #Iodine uptake [1.137] - SCFA administration stimulate #Retinoic acid (RA) production in the intestinal epithelium, a #vitamin #A derivate converted by #Aldehyde dehydrogenases, which is associated with signaling and expansion of peripheral Tregs (pTregs) in the context of a immunosuppressive response [1.138] - moderate levels of short-chain fatty acids may contribute to stabilizing intestinal permeability by directly influencing the distribution of tight junction proteins, high concentrations of these fatty acids may have the opposite effect [1.139] [#Multiple Sclerosis] - the abundances of several of the major short-chain fatty acid (SFCA) producers were decreased (#Prevotella and #Roseburia). - Dietary rhamnogalacturonan-I obtained by enzymatic treatment of #Carrot pomace has shown #Prebiotic properties. - cRG-I was degraded rapidly in the proximal colon compartment and fermentation became quicker and more complete during three weeks of repeated supplementation. - arabinan sidechains were utilized before the RG-I backbone, which correlated with an increase in #Bifidobacterium longum absolute abundance over the three weeks period. - Donor specific production of all SCFA increased over time with a general trend of higher levels of #Acetate and #Propionate than #Butyrate. [1.141] [#Amyloid-beta] - supplementation of SCFAs simulated the role of the microbiota and increased Aβ plaque burden [1.142] [#Diet Inflammatory Index] - microbiome members that were depleted in individuals reporting high DII scores included known producers of anti-inflammatory SCFAs such as #Faecalibacterium [1.143] - Consumption of green banana biomass seems to exert beneficial effects on intestinal function and potential effects on #Obesity, #Dyslipidemia, and diabetes. These effects may be related to increased fecal short-chain fatty acid concentrations as a result of type 3 #Resistant Starch present in biomass. [1.144] - The activation of G-protein-coupled receptors by SCFAs triggers the release of peptide YY and #GLP-1, contributing to feelings of satiety and reduced food intake. - SCFAs activate #Adenosine monophosphate-activated protein kinase, promoting hepatic autophagy and lipid oxidation. [1.145] [#Prebiotic, #Probiotic] - A 12-week multi-species synbiotic supplementation in patients with #Dyslipidemia resulted in significant increases in fecal SCFAs including #Acetate, #Butyrate, #Propionate, and #Valerate in the intervention group. [1.146] [#Clostridium cluster I] - cRG-I supplementation stimulates short-chain fatty acid producing bacteria. [1.147] [#Organophosphorus] - the production of SCFAs, specifically #Acetate, has been observed during bacterial degradation of OP pesticides. - #Acetate has been shown to enhance #Glycogen repletion in liver and skeletal muscle and to account for #Glucose intolerance [1.148] - adults with #Prediabetes > #Metformin > increased the abundance of GM SCFA-producing bacteria M (#Fusicatenibacter and #Blautia) - adults with #Prediabetes > linagliptin/#Metformin > Roseburia, Bifidobacterium, and [Eubacterium] hallii group. [1.149] [#Blautia coccoides] - B. coccoides stimulated mucus growth through the production of the short-chain fatty acids #Propionate and #Acetate via activation of the short-chain fatty acid receptor Ffar2References Notes (1) [1.154] (3) [1.155]
