Microbiome & Chronic Diseases

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Short Chain Fatty Acid ⇒ Acetate {60000047}

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Functional Type:[  ]
Anti-inflammatory, Anti-bacterial, Anti-cancer, Energy source, Enhancing Gut integrity


- Acetate is themost beneficially associated with glucose metabolism and cardiovascular health.

Shared Reference Notes

  • [1.1
    - Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90-day poor functional #Stroke outcomes even after adjustments.
  • [1.2] [#Hypertension
    - Elevated putative #Succinate-producing bacteria and acetate-producing bacteria > respectively, lower and higher mean arterial pressure in mouse - #Prevotella and #Klebsiella > overrepresented in individuals with pHTN or HTN.
  • [1.3
    - Acetate production is widely distributed among many bacterial populations
  • [1.4] [#Galactooligosaccharides & modified mogrosides Sweetener
    - Significant growth during the fermentation at 10 h of bacterial populations includes #Bifidobacterium, #Bacteroides, #Enterococcus, and #Clostridium coccoides. - significant increase in production of SCFA in mMV-GOS at 10 h of fermentation, mainly seen in acetate and #Propionate production
  • [1.5
    - Acetate induced browning in adipose tissue.
  • [1.6
    - Increases in acetate were associated with decreases in insulin and glucose.
  • [#High fibre plant protein-rich diet] - The plant protein-rich version had the strongest effect on acetate, the short chain fatty acid most beneficially associated with glucose metabolism and cardiovascular health.”
  • [1.7] [#High fibre diet
    - Increased maternal dietary microbiome-accessible fiber and SCFA exposure during pregnancy > reduced incidence of #Asthma in offspring which persists into adulthood. - Reduced dietary fiber intake > reduced serum acetate levels in pregnant women > increased frequency of coughing/wheezing during the child’s first year of life. - During pregnancy > SCFA (such as acetate) > cross the placenta and affect the expression of fetal lung genes, such as NPPA, > encodes ANP (a molecule related to epithelial biology and immune regulation).
  • [1.8
    - Acetate does not exclusively originate from the colon, it is also produced endogenously from fatty acid oxidation
  • [1.9] [#Stroke
    - Reduced SCFAs levels, especially acetate, were associated with an increased risk of 90-day poor functional outcomes even after adjustments.
  • [#Parkinson’s Disease] - Intestinal mucus layer is rich in protein mucin. #Akkermansia utilises mucin as a nutritional source and degrades it into SCFA acetate, which acts as a substrate for other beneficial bacteria to produce butyrate, an energy source for the intestinal epithelial cells. - #Akkermansia is a symbiont that degrades mucin and encourages cells to produce more mucin. - A compensatory effect of richness in #Akkermansia is possibly due to depleting cellulose-degrading bacteria in the PD gut
  • [1.11
    - children with #Autism, SCFA levels were differentially altered, with an increase in #Propionate and acetate and a decrease in #Butyrate levels. - rats fed with #Propionate exhibited phenotypic features similar to those of #Autism.
  • [#Hypertension] - Blood pressure > increased Acetate, #Butyrate, and #Propionate
  • [1.12] [#Short Chain Fatty Acid] [#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
  • [1.13] [#Neuromyelitis optica] [#Short Chain Fatty Acid
    - lower faecal SCFA levels in these patients, and a negative correlation between acetate and #Butyrate levels and disease severity.
  • [1.14] [#Short Chain Fatty Acid
    - SCFA levels were observed to be decreased in non-obese #Non-alcoholic fatty liver disease. - SCFAs help to inhibit the progress of NAFLD in a variety of ways. - As histone deacetylase inhibitors, #Propionate, acetate, and #Butyrate play an important role in NAFLD by decreasing chromatin-bound acetyl groups
  • [#Steatohepatitis] - Acetate, #Propionate, and #Butyrate have been shown to alleviate hepatic steatosis by activating AMP-activated protein kinase, expressing a fatty-acid oxidation gene, and inhibiting macrophage proinflammatory activation
  • [1.15] [#Alcohol Consumption
    - gut microbiota responds to #Ethanol-feeding by activating acetate dissimilation, not by metabolizing #Ethanol directly. - #Ethanol is not directly metabolized by the gut microbiota, and changes in the gut microbiota linked to #Ethanol are a side effect of elevated acetate levels.
  • [1.16] [#Short Chain Fatty Acid
    - 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,.
  • [1.17] [#Irritable bowel syndrome
    - #Lactobacillus paracasei CNCM I-1572 improves symptoms, modulates gut microbiota structure and function through the reduction of Rumicococcus with consequent increased levels of acetate and #Butyrate, and reduces intestinal immune activation in patients with IBS
  • [1.18] [#Antibiotic Therapy
    - In case of antibiotics treatment it decreases the production of SCFA like #Butyrate, #Propionate and acetate which increases inflammation.
  • [1.19] [#Multiple Sclerosis
    - concentrations of fecal SCFAs (i.e., acetate, #Butyrate and #Propionate) were decreased in RRMS patients, compared to healthy controls
  • [#Inulin-Type Fructans] - #Butyrate production may also be driven by bacteria unable to degrade inulin type fructans, but are capable of consuming acetate, producing #Butyrate, and utilising partially degraded carbohydrate from #Bifidobacteria.
  • [1.21] [#Gastric bypass surgery
    - Higher #Butyrate- and #Propionate-to-acetate ratios after the surgery compared to baseline indicates a shift in microbial metabolism from acetate production to #Butyrate and #Propionate production. - #Butyrate and #Propionate, which are known to induce satiety in animals and humans, were in greater concentrations in post-RYGB patients compared to nonsurgical controls.
  • [1.22] [#Multiple Sclerosis] [#Lipocalin-2
    - decreasing trend in serum acetate (a short-chain fatty acid) levels in MS Lcn-2-high patients compared to healthy donors (HDs). - a decrease in the relative abundance of #Blautia massiliensis was significantly associated with a reduction of acetate in the serum of MS patients.
  • [1.23] [#Short Chain Fatty Acid
    - 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] - CRC patients had lower stool concentrations of #Butyrate, while acetate concentrations were increased.
  • [1.24] [#Butyrate, #Propionate, #Short Chain Fatty Acid
    - #Inulin and #Rice bran promoted the production of all three SCFA
  • [1.25] [#Hepatectomy] [#Short Chain Fatty Acid
    - 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.
  • [#Short Chain Fatty Acid] [#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).
  • [1.26
    Acetate > enhances tight junction protein expression & anti-inflammatory cytokine production
  • [#Human breast milk, #Infants] Infant > Breastfeeding > decreased acetate and increased #Succinate
  • [1.27] [#Short Chain Fatty Acid
    - #Butyrate can also be synthesized by the gut microbiota from acetate and #Lactate, although the last is not considered a SCFAs
  • [#Depression] - self-reported depressive symptoms were positively associated with fecal acetate concentrations and negatively associated with #Butyrate and #Propionate levels.
  • [1.28] [#Clostridium perfringens
    - C. perfringens > production of exotoxin, #pfoA, has been shown to be regulated by short-chain fatty acids such as acetate and #Butyrate > inhibit #pfoA exotoxin.
  • [1.29
    - In rat and primary microglial cell cultures, the addition of acetate decreases pro-inflammatory cytokines and microglia activation.
  • [#Bifidobacteria, #Bifidobacterium adolescentis, #Bifidobacterium pseudocatenulatum] [#Fructooligosaccharides, #Human milk oligosaccharides, #Inulin] - 2′FL/LNnT were bifidogenic for both age groups, 3′SL/6′SL and FOS/IN were exclusively bifidogenic for children and adults, respectively. - 3′SL/6′SL stimulated B. pseudocatenulatum (abundant in children), FOS/IN enhanced B. adolescentis (abundant in adults). - increased acetate, #Propionate and #Butyrate (only in adults) with product- and age-dependent differences.
  • [1.31] [#Inflamatory bowel disease] [#Lactic acid
    - Patients with IBD have lower fecal levels of acetate, #Propionate and #Butyrate, and higher levels of lactic and #Pyruvic acids than healthy individuals
  • [#Inflamatory bowel disease] - Acetate and #Propionate activate cell surface receptor GPR43 to induce neutrophil chemotaxis. - GPR43 is anti-lipolysis and implicated in IBD.
  • [1.32
    - Acetate increases the expression of genes associated with DNL.
  • - Acetate promotes #Cholesterol and fatty acid synthesis, but inhibits GNG.
  • [#Obesity] - Acetate causes browning of white adipose tissue, thus energy expenditure through heat dissipation.
  • [#Obesity] - Acetate is a substrate for #Cholesterol and fatty acid synthesis, which inhibits gluconeogenesis - Acetate causes browning of white adipose tissue which increases the expression of genes associated with lipogenesis
  • [1.33] [#Diabetes Type 2] [#Glucose, #Short Chain Fatty Acid
    - SCFA acetate activates GPR43, promoting GLP-1 release from colonic L cells.
  • [1.34
    - Acetate stimulates the release of satiety hormones and acts as a satiety signal.
  • [1.35] [#Short Chain Fatty Acid] [#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.
  • [#Acute lymphoblastic leukemia] [#Bacteroides ovatus, #Pseudomonas aurantiaca, #Roseburia intestinalis, #Roseburia inulinivorans] - #Children with ALL exhibit reduced relative abundance of both #Butyrate-producing species (#Roseburia faecis, R. intestinalis, R. inulinivorans, #Anaerostipes hardus, #Faecalibacterium prausnitzii, #Eubacterium ramulus) and acetate-producing species (#Prevotella maculosa, P. aurantiaca, #Bacteroides uniformis, B. ovatus)
  • [#Human breast milk] - Lack of exclusive breastfeeding and early cessation is associated with reduced relative abundance of #Bifidobacterium spp and lower stool levels of acetate.
  • [1.36] [#Short Chain Fatty Acid
    - 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
  • [1.37] [#carrot-derived rhamnogalacturonan I, #Inulin] [#Carrot
    - cRG-I resulted in a significantly higher acetate (+40%), #Propionate (+22%), yet a lower gas production (–44%) compared to IN. - cRG-I could thus result in overall more robust beneficial effects, while also being better tolerated.
  • [1.38] [#Blood Brain Barrier Integrity] [#Short Chain Fatty Acid
    - 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.
  • [1.39] [#Bacteroides uniformis] [#Short Chain Fatty Acid] [#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.
  • [#Lacto-fermented vegetables] - LFV consumption had greater effects on the faecal metabolome, with higher abundances of #Butyrate, acetate, and #Valerate and significantly greater metabolome diversity.
  • [1.41
    - #Butyrate biosynthesis is regulated by different metabolic pathways, with either acetate or #Propionate as precursors, and is pH-sensitive, with high production rates observed at low colonic pH values
  • [#Lachnospiracea] - The relatively higher proportion of acetate and #Propionate in the #Inulin group could be partially explained by the higher abundance of #Parasutterella, #Bacteroides, and #Parabacteroides, and as well as the lower prevalence of Lachnospiraceae_NK4A136 and #Faecalibaculum
  • - #Butyrate production is enhanced in the presence of #Firmicutes, while #Bacteroidota favor acetate and #Propionate production
  • [1.42] [#Short Chain Fatty Acid
    - 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.
  • [1.43] [#Prostate cancer] [#Short Chain Fatty Acid
    - 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.
  • [1.44] [#Short Chain Fatty Acid
    - #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.
  • [1.45] [#Prostate cancer
    - #Ruminococcus can convert pregnenolone and hydroxypregnenolone to dehydroepiandrosterone (DHEA) and testosterone, which are downstream metabolites. - Abiraterone acetate, a specific inhibitor of CYP17A1, prevents the bacterial conversion of pregnenolone to DHEA and testosterone. - #Ruminococcus possesses genes with significant sequence similarity with human CYP17
  • [1.46] [#Attention Deficit Hyperactivity Disorder
    - The ADHD group showed significantly lower concentrations of fecal acetate and #Butyrate
  • [1.47
    - Acetate can be converted to acetyl-CoA, which is a substrate to synthesize fatty acids in hepatocytes
  • - #Propionate can inhibit lipid synthesis from acetate
  • [1.48] [#Anaerostipes hadrus, #Blautia wexlerae, #Eubacterium hallii, #Fusicatenibacter saccharivorans] [#Short Chain Fatty Acid
    - 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.
  • [1.49] [#Short Chain Fatty Acid
    - 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.
  • [#Bifidobacterium infantis] [#Para-cresol] - Antibitic resulted dysbiosis > Application of synbiotic #Bifidobacterium longum subspecies infantis (B. infantis), and #Human milk oligosaccharides (HMOs) > - increases in #Lactate-consuming #Veillonella, faster acetate recovery, and changes in #Indolelactate and p-cresol #Sulfate, metabolites that impact host inflammatory status. - #Veillonella co-cultured in vitro and in vivo with B. infantis and HMO converts #Lactate produced by B. infantis to #Propionate, an important mediator of host physiology.
  • [1.51
    - #Butyrate is produced by cross-feeding interactions between acetate-producing #Bifidobacterium spp. and acetate-utilizing #Faecalibacterium prausnitzii
  • [#Short Chain Fatty Acid] - Combination of SCFAs, mainly acetate, #Propionate, and #Butyrate, showed increased effects against #Colitis
  • [1.52] [#Short Chain Fatty Acid
    - 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.
  • [#Alzheimer’s disease] [#Amyloid-beta] - supplementation of acetate to the diet of a mouse model for AD induced the pro-inflammatory phenotype of microglia with elevated cytokine expression > suppress the phagocytosis by microglia in the presence of Aβ.
  • [#Alzheimer’s disease] - acetate regulate the release of #Neurotransmitters including #Glutamate, #Glutamine, and γ-amino butyric acid in the hypothalamus and increase the neuropeptide expression. - acetate, as a signaling metabolite that can enhance the maturation of microglia, maintain the homeostatic metabolic state, and regulate microglial phagocytosis and AD pathological progression during neurodegeneration
  • [1.53] [#Eubacterium limosum] [#Osteopontin
    - At 3 months, OPN was positively correlated with E. limosum, which can produce #Butyrate along with acetate, as the main fertilization end-product from #Methanol.
  • [1.54] [#Treponema medium] [#Hydrogen sulfide
    - Complete utilization of #Taurine as electron acceptor in modified #Desulfovibrio liquid medium with electron donors #Lactate and #Pyruvate in excess resulted in production of nearly quantitative amounts of H2S and excess acetate
  • [1.55] [#Acetylcholine
    - Acetate metabolism is an important metabolic pathway in many cancers and is controlled by acetyl-CoA synthetase 2 (ACSS2), an enzyme that catalyzes the conversion of acetate to acetyl-CoA. - blocking ACSS2, switches #Cancer cells from acetate consumers to producers of acetate thereby freeing acetate for tumor-infiltrating lymphocytes to use as a fuel source.
  • [1.56] [#Obesity
    - Endogenous acetate turnover was 30% higher in lean versus obese subjects, and increased plasma acetate turnover did not contribute to increased GSIS or #Ghrelin secretion in either group
  • [#Obesity] - gut microbiota exposed to high-calorie nutrients raise acetate levels in the animal, which activates the parasympathetic nervous system. - This increases #Ghrelin and #Glucose-stimulated insulin system (GSIS) secretion, which promotes appetite for high-calorie foods, resulting in a positive feedback cycle.
  • [1.57] [#TMA
    - #Lachnoclostridium could affect cardiometabolic health by lowering acetate levels and producing harmful lipid compounds, including trimethylamine and CDP-diacylglycerol

References Notes

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Common References