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PROVIDER: PRJNA1289205 | ENA |
REPOSITORIES: ENA
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Project description:Previous bioreactor studies achieved high volumetric n caprylate (i.e., n octanoate) production rates and selectivities from ethanol and acetate with chain elongating microbiomes. However, the metabolic pathways from the substrates to n caprylate synthesis were unclear. We operated two n caprylate producing upflow bioreactors with a synthetic medium to study the underlying metabolic pathways. The operating period exceeded 2.5 years, with a peak volumetric n caprylate production rate of 190 ± 8.4 mmol C L 1 d 1 (0.14 g L 1 h 1). We identified oxygen availability as a critical performance parameter, facilitating intermediate metabolite production from ethanol. Bottle experiments in the presence and absence of oxygen with 13C labeled ethanol suggest acetyl coenzyme A based derived production of n butyrate (i.e., n butanoate), n caproate (i.e., n hexanoate), and n caprylate. Here, we postulate a trophic hierarchy within the bioreactor microbiomes based on metagenomics, metaproteomics, and metabolomics data, as well as experiments with a Clostridium kluyveri isolate. First, the aerobic bacterium Pseudoclavibacter caeni and the facultative anaerobic fungus Cyberlindnera jadinii converted part of the ethanol pool into the intermediate metabolites succinate, lactate, and pyroglutamate. Second, the strict anaerobic C. kluyveri elongated acetate with the residual ethanol to n butyrate. Third, Caproicibacter fermentans and Oscillibacter valericigenes elongated n butyrate with the intermediate metabolites to n caproate and then to n caprylate. Among the carbon chain elongating pathways of carboxylates, the tricarboxylic acid cycle and the reverse ß oxidation pathways showed a positive correlation with n caprylate production. The results of this study inspire the realization of a chain elongating production platform with separately controlled aerobic and anaerobic stages to produce n caprylate renewably as an attractive chemical from ethanol and acetate as substrates.
2025-05-24 | PXD054148 | Pride
Project description:Stroek, Gabriëlss and co-workers identify key microbial species driving CO₂ conversion in biofilm-based microbial electrosynthesis (MES) systems that produce acetate, butyrate, and caproate via the Wood–Ljungdahl and reverse β-oxidation pathways. Metagenomic and metaproteomic analyses revealed Eubacterium limosum, Sporomusa sphaeroides, and Clostridium aromativorans as main contributors, with C. aromativorans newly linked to enhanced butyrate and caproate production.
2026-08-13 | PXD069469 | Pride
Project description:Vegetable oil enriched with n-caproate and n-caprylate via extractive lactate-based chain elongation
| PRJEB42300 | ENA
Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism. Mice were infused in cecum with stably-labelled isotopes of the three main short chain fatty acids or control solution. After 6 hrs, livers were removed and pooled RNA samples were subjected to gene expression profiling.
2013-10-21 | E-GEOD-45926 | biostudies-arrayexpress
Project description:Flavonifractor plautii, a prevalent gut commensal, uniquely combines flavonoid degradation with the capacity to produce health-promoting short-chain fatty acids (SCFAs), notably butyrate and propionate. However, its metabolic pathways, ecological roles, and health impacts remain poorly characterized. To explore its probiotic potential and ecological functions, we developed a genome-scale metabolic model (GEM), iFP655, using automated reconstruction, deep-learning-based gap-filling, thermodynamic constraints, and transcriptomics. The iFP655 model substantially improved the predictions of growth rates and SCFA profiles compared to previous models. Simulations identified acetyl-CoA pathways as the preferred route for butyrate production, whereas the energetically costly lysine pathway remained inactive despite robust gene expression. Propionate synthesis occurred primarily via the methylmalonyl-CoA pathway. Community metabolic modeling with with representative species of a Western minimal gut microbiota highlighted F. plautii ‘s contributions to enhanced SCFA production, especially butyrate, amino acid metabolism, and syntrophic interactions driven by dietary substrates. Our findings indicate that diet-driven syntrophy significantly shapes microbial community structure and function, underscoring the ecological importance of F. plautii in gut microbial interactions and highlighting its potential as a probiotic candidate to beneficially modulate gut microbiota through dietary interventions.
2026-03-15 | MODEL2602030001 | BioModels
Project description:Gut microbiota are recognized to be important for anticancer therapy, yet the underlying mechanism is not clear. Herein, we demonstrate that gut microbial metabolite butyrate improves anticancer therapy efficacy by regulating intracellular calcium homeostasis. Butyrate metabolism is activated in hepatocellular carcinoma (HCC) patients. Butyrate supplementation or depletion of short-chain Acyl-CoA dehydrogenase (ACADS), a key enzyme for butyrate metabolism, significantly inhibit HCC proliferation and metastasis. Profiling analysis of genes upregulated by butyrate supplementation or ACADS knockdown reveal that calcium signaling pathway is activated, leading to dysregulation of intracellular calcium homeostasis and production of reactive oxygen species (ROS). Butyrate supplementation improves the therapy efficacy of a tyrosine kinase inhibitor sorafenib. Butyrate and sorafenib co-encapsulated monomethoxy (polyethylene glycol)-poly (D, L-lactide-co-glycolide)-poly(L-lysine)-glypican 3 (PEAL-GPC3) nanoparticles significantly reduce HCC progression. Our findings provide new insight into the mechanisms that the gut microbial metabolites inhibit HCC progression and suggest a translatable therapeutics approach to enhance the clinical targeted therapeutic efficacy.
2025-07-20 | GSE210156 | GEO
Project description:Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
2013-10-21 | GSE45926 | GEO
Project description:Short-chain fatty acids (SCFAs) butyrate and propionate are metabolites from dietary fibers fermentation by gut microbiota that can affect differentiation or functions of T cells, macrophages and dendritic cells. We show here that these SCFAs directly impact B cells to modulate in a dose-dependent fashion AID and Blimp1 expression, class-switch DNA recombination, somatic hypermutation and plasma cell differentiation, thereby impairing, through B cell-intrinsic activity, local (intestinal) and systemic T-dependent and T-independent antibody responses. In human and mouse B cells, butyrate and propionate upregulate select miRNAs that target Aicda and Prdm1 mRNA-3’UTRs through epigenetic inhibition of histone deacetylation of the respective miRNA host genes. Further, they modulate B cell Aicda and Prdm1 by acting as HDAC inhibitors, not as energy substrate or through GPR-engagement signaling. Finally, butyrate and propionate epigenetic impact on B cells extends to inhibition of autoantibody production and autoimmunity in lupus MRL/Faslpr/lpr and NZB/WF1 mice.
2020-01-13 | GSE140111 | GEO
Project description:Lactate-based microbial chain elongation for n-caproate and iso-butyrate production: genomic and metabolic features of three novel Clostridia isolates
| PRJEB39379 | ENA