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Short Chain Fatty Acid {60000042}

Record Keys
Parent:[  ]
Definition:
Short Chain Fatty Acid
Queue:[  ]

Details
Initialisation date:
2020-09-17
Specification:

SCFA

Source:
[  ]

Links

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-fiber 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 (IPA)] 
    - 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.
  • - SCFAs can restore the function of the blood-brain barrier in patients with #Multiple Sclerosis.
  • [#Non-alcoholic 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.
  • [#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
  • - 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] 
    - 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] [#CVD] [#Bile Acids, #Primary bile acids, #Secondary bile acids, #TMA, #TMAO] 
  • [1.44] 
    - #Ginger root consumption could increase Bifidobacterium spp., enhance faecal SCFA production as well as invoke anti-#Obesity effects in obese mice
  • [1.45] [#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.
  • [1.46] [#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.
  • [1.47] [#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.
  • [1.48] [#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 (PE), #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.
  • [1.49] [#Alzheimer’s disease] [#Brain-derived tau] [#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.
  • [#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.
  • [1.51] 
    - 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.
  • [1.52] [#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
  • [1.53] [#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
  • [1.54] [#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.
  • [1.55] [#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.
  • [1.56] [#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).
  • [1.57] [#Epigallocatechingallat] 
    - ECGC contribute significantly also to increase the number of SCFAs-producing bacteria, especially #Akkermansia, enhancing the colon barrier integrity and general anti-inflammatory effects.

References Notes

  • (1) [1.64] 
  • (2) [1.65] 
  • (3) [1.66] 

Common References