Short Chain Fatty Acid ⇒ Propionate {60000046}

Shared Reference Notes

• [1.1] 
  - Propionate interacts with a type of immune system cell mononuclear phagocytes that are also found in the lining of the gut which cascade sets of inflammation.
• [1.2] 
  - Propionate induce glycogenolysis and hyperglycaemia via the upregulation of glucagon and fatty acid-binding protein 4 (FABP4), thereby hindering the effects of insulin.
• [1.3] 
  - High doses of propionate, in young rats, induced a neuroinflammatory response and behavioral alterations.
• [1.4] 
  - propionate is restricted to certain microorganisms belonging to the phylum Firmicutes or Akkermansia muciniphilla
• [1.5] 
  - The abundance of #Akkermansia muciniphila, as a key player of propionate production, is associated with the richness of the gut microbiota in patients with #Breast cancer
• [1.6] [#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
• [1.7] 
  - Propionate was shown to stimulate PYY and GLP-1 release thereby reducing energy intake.
• [1.8] [#Hypertension] 
  - Propionate treatment in mice > antihypertensive effect.
• [1.9] 
  - Increases in propionate with increases in leptin, LDL cholesterol, and blood pressure.
• [#Eosinophilic esophagitis] - Propionate > restore the barrier function of esophageal epithelial cells after an inflammatory insult
• [1.11] [#Short Chain Fatty Acid] 
  - #Butyrate or propionate, but not acetate > rapidly converted to the corresponding acyl-CoAs > used by p300 to catalyze auto-acylation of the autoinhibitory loop > activate the acetyltransferase p300 > activating the enzyme for histone/protein acetylation > rapid and sustained increases in histone acetylation.
• [1.12] [#Obesity] 
  - Maternal consumption of #Sweeteners > altered cecal microbial composition and metabolism of propionate/#Lactate in their offspring. - Offspring daily body weight gain, liver weight and body fat > correlate positively to the relative abundance of key microbes and enzymes involved in #Succinate/propionate production while negatively correlated to that of #Lactose degradation and #Lactate production. - The altered propionate/#Lactate production in the cecum of weanlings from aspartame and stevia consuming dams implicates an altered ratio of dietary carbohydrate digestion, mainly #Lactose, in the small intestine vs. microbial fermentation in the large intestine.
• [1.13] [#Propionibacterium freudenreichii] 
  - P. freudenreichii is able to reduce pyruvate into propionate
• [1.14] 
  - 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
• [1.15] [#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
• [1.16] 
  - Propionate and #Butyrate regulate gene expression by directly inhibiting histone deacetylases (HDACs)
• [#Metabolic associated fatty liver disease] [#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
• [1.17] [#Irritable bowel syndrome] 
  - a recent meta-analysis identified low levels of propionate and #Butyrate in feces from patients with IBS-C, as compared with healthy controls, and a higher proportion of #Butyrate in fecal samples of patients with IBS-D, as compared with controls
• [1.18] [#Antibiotic Therapy] 
  - In case of antibiotics treatment it decreases the production of SCFA like #Butyrate, propionate and #Acetate which increases inflammation.
• - Propionate serves as satiety molecule and facilitates production of ATP in liver.
• [1.19] [#Multiple Sclerosis] 
  - concentrations of fecal SCFAs (i.e., #Acetate, #Butyrate and propionate) were decreased in RRMS patients, compared to healthy controls
• [#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.
• [#Diabetes Type 2] [#Gastric bypass surgery] - An increase in propionate and #Bile Acids after RYGB was associated with an increase in hormone peptide tyrosine tyrosine (PYY) in humans and, hence, resolution of diabetes.
• [1.21] [#CVD] 
  - Patients with CAD had lower concentrations of propionate compared to patients without CAD. - increase of propionate concentration was associated with reduced risk for CAD. - Propionate serum concentrations elicit an immunomodulation with increases of regulatory T cells.
• - Persons with #Hypertension had lower propionate concentrations
• [1.22] [#Short Chain Fatty Acid] [#Infants] 
  - a higher percentage of propionate in relation to total SCFA composition was associated with longer uninterrupted human infant #Sleep
• [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.
• [1.24] [#Diabetes Type 2] 
  - The genus #Blautia was one of the most represented genera in both groups enriched in group T2D. - #Lachnoclostridium were more abundant in the microbiome profiles of diabetic patients. - There are anomalies in the genera #Bacteroides and #Prevotella, both of which are increased in the T2D, both genera are propionate producers.
• [1.25] [#Acetate, #Butyrate, #Short Chain Fatty Acid] 
  - #Inulin and #Rice bran promoted the production of all three SCFA
• - resistant #Maltodextrin was highly propiogenic
• [1.26] [#Infants] 
  Infant > Solid foods: Increased Propionate and #Butyrate
• Propionate > substrate for gluconeogenesis in intestine and liver
• [1.27] [#Depression] 
  - self-reported depressive symptoms were positively associated with fecal #Acetate concentrations and negatively associated with #Butyrate and propionate levels.
• [1.28] 
  - #Parabacteroides distasonis and #Akkermansia muciniphila have the highest PS for producing propionate through the fermentation of #Pyruvate.
• - in a mouse model of #Alzheimer’s disease, increased gut microbiota-produced propionate correlates with neuroinflammation and cognitive decline
• [1.29] [#Obstructive sleep apnea-hypopnea syndrome] 
  - OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. - the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from #Lactate.
• [#Human milk oligosaccharides] [#Adult] - Among the HMOs, 6′SL specifically stimulated propionate (linked to #Bacteroides fragilis in #Children and #Phocaeicola massiliensis in adults)
• [#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] 
  - Propionate promotes GNG, satiety, less food intake and minor #Cholesterol synthesis.
• [#Obesity] - Propionate is used as a substrate for gluconeogenesis, which increases energy expenditure and reduces food intake and #Cholesterol synthesis.
• [1.33] [#Diabetes Type 2] [#Glucose] 
  - activation of GPR41 by propionate or #Butyrate can induce both GLP-1 and peptide YY secretion from L cells in the small intestine.
• [1.34] [#Veillonella atypica] [#Exercise training] 
  - V. atypica improves run time via its metabolic conversion of exercise-induced #Lactate into propionate.
• [1.35] [#Short Chain Fatty Acid] [#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.
• [1.36] [#Alzheimer’s disease] [#Short Chain Fatty Acid] 
  - #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.
• [1.37] 
  - exposure to the fungicide propamocarb, which similarly to thymol targets disruption of the cell membrane, increased propionate, #Isobutyrate and #Bile Acids in faeces of exposed mice according to a faecal metabolomics analysis.
• [1.38] [#High Fat Diet] 
  - the levels of #Butyrate and propionate show obvious daily oscillations. Moreover, these oscillations are lost under high-fat diets.
• [1.39] [#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.
• [#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.
• [1.41] [#CVD] [#Streptococcus] 
  - CACS-associated species was negatively associated with the microbially derived #Tryptophan metabolite #Indole propionate, a metabolite that has been found inversely associated with atherosclerotic coronary disease in humans and reduced progression of #Atherosclerosis in mice.
• [1.42] [#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.
• [1.43] 
  - #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
• - a positive association of propionate with the phylum #Bacteroidota and many of its genera, including #Bacteroides and #Parabacteroides.
• [#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
• - propionate biosynthesis at phylum level occurs via two modes: the #Lactate pathway regulated by #Firmicutes and the #Succinate pathway by #Bacteroidetes
• - #Butyrate production is enhanced in the presence of #Firmicutes, while #Bacteroidota favor #Acetate and propionate production
• - #Lentils (LEN) and #Chickpeas (CKP) increase #Butyrate, while #Inulin (INU) promotes propionate. - #Bile Acids and #Cholesterol are reduced in #Prebiotic groups along with suppressed #Choline-to-trimethylamine conversion by LEN and CKP
• [1.44] [#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.
• - Propionate is produced by some #Firmicutes, #Bacteroidetes, and #Verrucomicrobia, especially #Akkermansia muciniphila
• [1.45] 
  - #Vitamin B12 is a cofactor for the enzyme methylmalonyl-CoA mutase (MCM), which converts succinyl-CoA to methylmalonate in the #Succinate-propionate pathway. - Limiting #Vitamin B12 levels can lead to an accumulation of #Succinate.
• [1.46] [#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.
• [1.47] [#Prostate cancer] [#Carbohydrate diet] 
  - The use of propionates decreases the probability of human PCA spreading. - The intestinal flora processes these three metabolites of a high-carbohydrate meal
• [1.48] 
  - Propionate can inhibit lipid synthesis from #Acetate
• [1.49] [#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.
• [#Short Chain Fatty Acid] - Combination of SCFAs, mainly #Acetate, propionate, and #Butyrate, showed increased effects against #Colitis
• [1.51] [#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.
• [#Potasium] - Propionate and #Butyrate exert a distinct influence on the intracellular K+ levels
• [1.52] [#Short Chain Fatty Acid] 
  - #Kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (#Butyrate), and in the brain (#Butyrate and propionate).
• [1.53] [#Colorectal cancer] 
  - #Butyrate and propionate directly upregulate genes involved in cytokine production, antigen processing and MHCI generation in CRC cells, all of which contribute to CD8+ T cell activation. - The activated CD8+ T cells secrete high amounts of IFNγ which then feeds back on the cancer cells to further upregulate CRC cell MHCI, further increasing their capacity to activate CD8+ T cells. - #Butyrate and propionate induced greater DNA damage in the DNA repair deficient MSI CRC cells, which are typically quite immunogenic.
• [1.54] [#Exercise training] 
  - Fecal #Turicibacter, #Allobaculum, and #Clostridium sensu stricto, and propionate in the cecum were decreased by the exercise.
• [#Depression] [#Exercise training] - Voluntary exercise-induced antidepressant properties might be partially caused by suppression of #Serotonin uptake into gut microbiota and increase the permeability of the blood-brain barrier via reduced propionate production.
• [1.55] 
  - #Fusicatenibacter has a strong correlation with higher levels of propionate in fecal samples. - This correlation was linked to unhealthy dietary habits and #Obesity
• [1.56] [#Multiple Sclerosis] 
  - Particularly propionate supplementation has shown immunomodulatory effects in people, lowering Th17 cells and raising T reg. - In MS patients, long-term propionate supplementation lowered relapse rates, stabilized disability, and stopped brain shrinkage
• [1.57] [#Plant Microbiome] 
  - Genes encoding propionate CoA-transferase and #Butyrate kinase that are involved in propionate and #Butyrate biosynthesis, respectively, were only detected in a small number of MAGs that belong to #Burkholderiales and #Rhizobiales.
• [1.58] [#Blood Brain Barrier Integrity] [#Short Chain Fatty Acid] 
  - SCFAs can cross the BBB and activate (propionate) or inhibit microglia in addition to favoring the inflammatory process.
• [1.59] 
  - the decrease in the #Acetate ratio in the gut, coupled with the utilization of #Butyrate before it reaches systemic circulation, can indirectly lead to an increase in the ratio of propionate. As a result, the relative proportion of propionate in the bloodstream may appear higher due to these dynamic changes in #Acetate and #Butyrate metabolism.
• [#Alpha-synuclein] - Supplementation of propionate protected neurons from α-syn-induced neurodegeneration.
• [#Vitamin B12] - B12 appears to increase propionate and #Butyrate production by the human gut microbiota while also serving as a coenzyme of methylmalonyl-CoA mutase to break down propionate.
• [#Vitamin B12] - Unlike #Curli, B12 does not affect α-syn aggregation (Figure S1) and modulates neurodegeneration downstream of α-syn by inducing the breakdown of propionate, which is a key activator of metabolic genes involved in fatty acid and amino acid metabolism and energy production. - Removing B12 or supplementing propionate in the diet could metabolically rescue neurodegeneration without reversing α-syn aggregation, indicating the possibility of treating neurodegenerative diseases by simply changing the level of certain metabolites.
• [#Parkinson’s Disease] [#Dopamine] - PA increased the survival of mouse primary DA neurons against rotenone-induced toxicity, - #Butyric acid rescued α-syn overexpression-induced DNA damage in Lund human mesencephalic cells. - In mouse PD models, oral supplementation of propionate and #Butyrate also protected neurons from chemically induced degeneration and ameliorated motor impairments.
• [#Parkinson’s Disease] - propionate and #Butyrate are inhibitors of histone deacetylase> may reshape the transcriptional landscape by modulating histone modifications. - The fact that propionate altered the expression of thousands of genes in the PD animals supports its role in reprogramming the transcriptome. - propionate-induced transcriptional changes boost mitochondrial functions and ATP-linked respiration
• [1.61] [#Inositol Lipids] 
  - significant proportion of #Anaerostipes species tested have the ability to convert inositol into propionate, potentially offering advantageous effects on health
• [1.62] [#Bacteroides dorei, #Lachnoclostridium clostridioforme] 
  - L. clostridioforme was observed to be essential for propionate production, and B. dorei for #Lactate production.
• [1.63] 
  - #Akkermansia muciniphila facilitates mucin and produces #Folate, propionate, and #Acetate
• [1.64] [#Short Chain Fatty Acid] 
  - 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.
• [1.65] 
  - A marked reduction in #Butyrate and propionate biosynthesis and corresponding metabolic changes were confirmed in relapsing remitting #Multiple Sclerosis (RRMS) compared with HCs.
• [1.66] [#Short Chain Fatty Acid] [#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.
• [1.67] [#Blautia coccoides] [#Short Chain Fatty Acid] 
  - 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 Ffar2
• [1.68] [#Veillonella atypica] [#Athletes, #Sport] 
  - increase in #Veillonella relative abundance in marathon runners postmarathon. - #Veillonella utilize #Lactate as their sole carbon source > at higher relative abundance postexercise > convert #Lactate to propionate. - V. atypica improves run time via its metabolic conversion of exercise-induced #Lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance. - intrarectal instillation of propionate in mouse is sufficient to reproduce the increased treadmill run time performance observed with V. atypica gavage.

References Notes