Transport of acetate and butyrate in the hind-gut of rabbits.
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ABSTRACT:
SUBMITTER: Henning SJ
PROVIDER: S-EPMC1174517 | biostudies-other | 1972 Dec
REPOSITORIES: biostudies-other
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Project description:1. When studied in vitro, tissue from the caecum and the proximal colon of rabbits converted butyrate into ketone bodies. The conversion was similar to that observed with liver slices. The ketogenic activity was associated with the mucosa rather than the muscle of the gut wall and, in the colon, diminished as the distance from the caecal-colonic junction increased. 2. Tissue from the wall of the ileum, caecum, proximal colon and distal colon was also shown to metabolize [1-(14)C]butyrate to carbon dioxide. 3. Enzyme assays showed that in both liver tissue and caecal mucosa the activity of hydroxymethylglutaryl-CoA synthase was more than ten times that of acetoacetyl-CoA deacylase. Labelling experiments in vitro gave confirmation of the hydroxymethylglutaryl-CoA pathway. 4. The significance of the conversion of butyrate into ketone bodies is discussed.
| S-EPMC1174516 | biostudies-other
Project description:Cellulose acetate butyrate (CAB) is a possible candidate, being a raw material derived from renewable resources, to replace fossil-based materials. This is due to its thermoplastic properties and the relative ease with which it could be implemented within the existing industry. With a significant amount of variation in CAB on the market today, a knowledge gap has been identified regarding the understanding of the polymer structural arrangement in films. This relates to the underlying mechanisms that regulate CAB film material properties, insights that are important in product development. In this study, commercially available CAB was investigated with XRD, SEM, AFM, and TOPEM DSC in order to obtain physicochemical information related to its micro-structural features in solvent-cast films. The film-forming ability relates mostly to the number of hydroxyl groups, and the semi-crystallinity of the films depends on the type and position of the side groups along the cellulose backbone. The appearance of signs of possible cholesteric ordering in the films could be connected to higher amounts of hydroxyl groups along the backbone that disturb the helix arrangement, while the overall order was primarily related to the butyrate substitution and secondarily related to the molecular weight of the particular CAB studied. Cold crystallization was also observed in one CAB sample.
| S-EPMC10181278 | biostudies-literature
Project description:Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. To advance this therapeutic towards clinical application, we tested this therapy in an advanced model of hindlimb ischemia in rabbits with hyperlipidemia and diabetes. This model has therapeutic resistance to angiogenic therapies and maintains long term deficits in recovery from ischemic injury. We treated rabbits with local treatment with tmSCF nanodiscs or control solution delivered locally from an alginate gel delivered into the ischemic limb of the rabbits. After eight weeks, we found significantly higher vascularity in the tmSCF nanodisc-treated group in comparison to alginate treated control as quantified through angiography. Histological analysis also showed a significantly higher number of small and large blood vessels in the ischemic muscles of the tmSCF nanodisc treated group. Importantly, we did not observe inflammation or mast cell activation in the rabbits. Overall, this study supports the therapeutic potential of tmSCF nanodiscs for treating peripheral ischemia.
| S-EPMC10825164 | biostudies-literature
Project description:Host diet influences the diversity and metabolic activities of the gut microbiome. Previous studies have shown that the gut microbiome provides a wide array of enzymes that enable processing of diverse dietary components. Because the primary diet of the porcupine, Erethizon dorsatum, is lignified plant material, we reasoned that the porcupine microbiome would be replete with enzymes required to degrade lignocellulose. Here, we report on the bacterial composition in the porcupine microbiome using 16S rRNA sequencing and bioinformatics analysis. We extended this analysis to the microbiomes of 20 additional mammals located in Shubenacadie Wildlife Park (Nova Scotia, Canada), enabling the comparison of bacterial diversity amongst three mammalian taxonomic orders (Rodentia, Carnivora, and Artiodactyla). 16S rRNA sequencing was validated using metagenomic shotgun sequencing on selected herbivores (porcupine, beaver) and carnivores (coyote, Arctic wolf). In the microbiome, functionality is more conserved than bacterial composition, thus we mined microbiome data sets to identify conserved microbial functions across species in each order. We measured the relative gene abundances for cellobiose phosphorylase, endoglucanase, and beta-glucosidase to evaluate the cellulose-degrading potential of select mammals. The porcupine and beaver had higher proportions of genes encoding cellulose-degrading enzymes than the Artic wolf and coyote. These findings provide further evidence that gut microbiome diversity and metabolic capacity are influenced by host diet.
| S-EPMC5744928 | biostudies-literature
Project description:Disruptions to the gut-brain-axis have been linked to neurodegenerative disorders. Of these disruptions, reductions in the levels of short-chain fatty acids (SCFAs), like butyrate, have been observed in mouse models of Alzheimer's disease (AD). Butyrate supplementation in mice has shown promise in reducing neuroinflammation, amyloid-β accumulation, and enhancing memory. However, the underlying mechanisms remain unclear. To address this, we investigated the impact of butyrate on energy metabolism in mouse brain slices, primary cultures of astrocytes and neurons and in-vivo by dynamic isotope labelling with [U-13C]butyrate and [1,2-13C]acetate to map metabolism via mass spectrometry. Metabolic competition assays in cerebral cortical slices revealed no competition between butyrate and the ketone body, β-hydroxybutyrate, but competition with acetate. Astrocytes favoured butyrate metabolism compared to neurons, suggesting that the astrocytic compartment is the primary site of butyrate metabolism. In-vivo metabolism investigated in the 5xFAD mouse, an AD pathology model, showed no difference in 13C-labelling of TCA cycle metabolites between wild-type and 5xFAD brains, but butyrate metabolism remained elevated compared to acetate in both groups, indicating sustained uptake and metabolism in 5xFAD mice. Overall, these findings highlight the role of astrocytes in butyrate metabolism and the potential use of butyrate as an alternative brain fuel source.
| S-EPMC11563520 | biostudies-literature
Project description:1. Interactions in the rates of consumption of acetate, propionate and butyrate in sheep liver mitochondria were examined in the presence and absence of l-malate and alpha-oxoglutarate. 2. Acetate was not consumed in absence of ancillary substrate but utilization of acetate (7.2nmol/min per mg of protein) occurred in the presence of alpha-oxoglutarate. This consumption was abolished by propionate or butyrate but the presence of acetate did not affect consumption of propionate or butyrate. 3. Propionate consumption (10.1nmol/min per mg of protein) was unaffected by malate but was stimulated by 63% by butyrate or by 180% by alpha-oxoglutarate. 4. Butyrate consumption (3.3nmol/min per mg of protein) was stimulated by 117% by malate, by 151% by propionate and by 310% by alpha-oxoglutarate. 5. In the absence of ancillary substrates the maximum rate of total volatile fatty acid utilization (24.7nmol/min per mg of protein) occurred with a mixture of propionate and butyrate. When both propionate and butyrate were present total consumption was not affected by malate but was stimulated by 24% by alpha-oxoglutarate. With alpha-oxoglutarate present, propionate and butyrate each decreased the other's consumption by about 26%, but the total utilization was the greatest observed. 6. The inhibition of acetate consumption by propionate or butyrate is unexplained, but the remaining effects are consistent with an interaction of propionate and butyrate through oxaloacetate together with a general limitation imposed by a need for GTP to rephosphorylate AMP formed during activation of the volatile fatty acids.
| S-EPMC1177274 | biostudies-other
Project description:The gut microbiome and its metabolites are increasingly implicated in several cardiovascular diseases, but their role in human myocardial infarction (MI) injury responses have yet to be established. To address this, we examined stool samples from 77 ST-elevation MI (STEMI) patients using 16 S V3-V4 next-generation sequencing, metagenomics and machine learning. Our analysis identified an enriched population of butyrate-producing bacteria. These findings were then validated using a controlled ischemia/reperfusion model using eight nonhuman primates. To elucidate mechanisms, we inoculated gnotobiotic mice with these bacteria and found that they can produce beta-hydroxybutyrate, supporting cardiac function post-MI. This was further confirmed using HMGCS2-deficient mice which lack endogenous ketogenesis and have poor outcomes after MI. Inoculation increased plasma ketone levels and provided significant improvements in cardiac function post-MI. Together, this demonstrates a previously unknown role of gut butyrate-producers in the post-MI response.
| S-EPMC10636175 | biostudies-literature
Project description:BackgroundAcetate is the major source of methane in nature. The majority of investigations have focused on acetotrophic methanogens for which energy-conserving electron transport is dependent on the production and consumption of H₂ as an intermediate, although the great majority of acetotrophs are unable to metabolize H₂. The presence of cytochrome c and a complex (Ma-Rnf) homologous to the Rnf (Rhodobacter nitrogen fixation) complexes distributed in the domain Bacteria distinguishes non-H₂-utilizing Methanosarcina acetivorans from H₂-utilizing species suggesting fundamentally different electron transport pathways. Thus, the membrane-bound electron transport chain of acetate-grown M. acetivorans was investigated to advance a more complete understanding of acetotrophic methanogens.ResultsA component of the CO dehydrogenase/acetyl-CoA synthase (CdhAE) was partially purified and shown to reduce a ferredoxin purified using an assay coupling reduction of the ferredoxin to oxidation of CdhAE. Mass spectrometry analysis of the ferredoxin identified the encoding gene among annotations for nine ferredoxins encoded in the genome. Reduction of purified membranes from acetate-grown cells with ferredoxin lead to reduction of membrane-associated multi-heme cytochrome c that was re-oxidized by the addition of either the heterodisulfide of coenzyme M and coenzyme B (CoM-S-S-CoB) or 2-hydoxyphenazine, the soluble analog of methanophenazine (MP). Reduced 2-hydoxyphenazine was re-oxidized by membranes that was dependent on addition of CoM-S-S-CoB. A genomic analysis of Methanosarcina thermophila, a non-H2-utilizing acetotrophic methanogen, identified genes homologous to cytochrome c and the Ma-Rnf complex of M. acetivorans.ConclusionsThe results support roles for ferredoxin, cytochrome c and MP in the energy-conserving electron transport pathway of non-H₂-utilizing acetotrophic methanogens. This is the first report of involvement of a cytochrome c in acetotrophic methanogenesis. The results suggest that diverse acetotrophic Methanosarcina species have evolved diverse membrane-bound electron transport pathways leading from ferredoxin and culminating with MP donating electrons to the heterodisulfide reductase (HdrDE) for reduction of CoM-S-S-CoB.
| S-EPMC3160891 | biostudies-literature
Project description:Islet dysfunction mediated by oxidative and mitochondrial stress contributes to the development of type 1 and 2 diabetes. Acetate and butyrate, produced by gut microbiota via fermentation, have been shown to protect against oxidative and mitochondrial stress in many cell types, but their effect on pancreatic β-cell metabolism has not been studied. Here, human islets and the mouse insulinoma cell line MIN6 were pre-incubated with 1, 2, and 4 mM of acetate or butyrate with and without exposure to the apoptosis inducer and metabolic stressor streptozotocin (STZ). Both short-chain fatty acids (SCFAs) enhanced the viability of islets and β-cells, but the beneficial effects were more pronounced in the presence of STZ. Both SCFAs prevented STZ-induced cell apoptosis, viability reduction, mitochondrial dysfunction, and the overproduction of reactive oxygen species (ROS) and nitric oxide (NO) at a concentration of 1 mM but not at higher concentrations. These rescue effects of SCFAs were accompanied by preventing reduction of the mitochondrial fusion genes MFN, MFN2, and OPA1. In addition, elevation of the fission genes DRP1 and FIS1 during STZ exposure was prevented. Acetate showed more efficiency in enhancing metabolism and inhibiting ROS, while butyrate had less effect but was stronger in inhibiting the SCFA receptor GPR41 and NO generation. Our data suggest that SCFAs play an essential role in supporting β-cell metabolism and promoting survival under stressful conditions. It therewith provides a novel mechanism by which enhanced dietary fiber intake contributes to the reduction of Western diseases such as diabetes.
| S-EPMC7073211 | biostudies-literature
Project description:Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions.
| S-EPMC10716539 | biostudies-literature