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Faecalibacterium duncaniae strain:A2-165

ABSTRACT: Reference genome for the Human Microbiome Project

PROVIDER: PRJNA18199 | ENA |

REPOSITORIES: ENA

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Project description:BACKGROUND: The gut microbiota plays an important role in human health and disease by acting as a metabolic organ. Metagenomic sequencing has shown how dysbiosis in the gut microbiota is associated with human metabolic diseases such as obesity and diabetes. Modeling may assist to gain insight into the metabolic implication of an altered microbiota. Fast and accurate reconstruction of metabolic models for members of the gut microbiota, as well as methods to simulate a community of microorganisms, are therefore needed. The Integrated Microbial Genomes (IMG) database contains functional annotation for nearly 4,650 bacterial genomes. This tremendous new genomic information adds new opportunities for systems biology to reconstruct accurate genome scale metabolic models (GEMs). RESULTS: Here we assembled a reaction data set containing 2,340 reactions obtained from existing genome-scale metabolic models, where each reaction is assigned with KEGG Orthology. The reaction data set was then used to reconstruct two genome scale metabolic models for gut microorganisms available in the IMG database Bifidobacterium adolescentis L2-32, which produces acetate during fermentation, and Faecalibacterium prausnitzii A2-165, which consumes acetate and produces butyrate. F. prausnitzii is less abundant in patients with Crohn's disease and has been suggested to play an anti-inflammatory role in the gut ecosystem. The B. adolescentis model, iBif452, comprises 699 reactions and 611 unique metabolites. The F. prausnitzii model, iFap484, comprises 713 reactions and 621 unique metabolites. Each model was validated with in vivo data. We used OptCom and Flux Balance Analysis to simulate how both organisms interact. CONCLUSIONS: The consortium of iBif452 and iFap484 was applied to predict F. prausnitzii's demand for acetate and production of butyrate which plays an essential role in colonic homeostasis and cancer prevention. The assembled reaction set is a useful tool to generate bacterial draft models from KEGG Orthology.

Project description:Several gut microbial species within the Faecalibacterium genus have emerged as promising next-generation probiotics (NGP) due to their multifunctional protective effects against gastrointestinal and systemic disorders. To enable clinical studies and further applications, improved methods for cultivating Faecalibacterium must be developed in compliance with current Good Manufacturing Practice regulations, which is complicated by its oxygen sensitivity and complex nutritional requirements. Different yeast-based nutrients (YBNs), including yeast extracts (YEs) and yeast peptones (YPs), are ubiquitously used when cultivating microbes to supply a broad range of macro- and micronutrients. In this study, we evaluated six experimental YBNs, namely three YEs, two YPs and a yeast cell wall product (YCW), and eight B-vitamins in the cultivation of Faecalibacterium duncaniae A2-165, former Faecalibacterium prausnitzii, using growth assays in microtitre plates, dose-effect studies in Hungate tube fermentations and fully controlled bioreactor experiments. We demonstrated that YEs promote F. duncaniae A2-165 growth in a nutritionally limited medium, while YPs and YCW lacked essential growth factors for enabling cell propagation. High cell density was obtained in controlled bioreactors using a medium containing 2-4% of a selected YE and 1% casein peptone (3.4 ± 1.7 × 109 -5.1 ± 1.3 × 109 cells mL-1 ). Among all tested B-vitamins, we identified B5 as a strong growth promoter. Replacing casein peptone with YP and supplementing with vitamin B5 further increased biomass by approximately 50% (6.8 ± 1.7 × 109 cells mL-1 ). Hence, empirical selection of YE, YP and B5 allowed formulation of a high-yielding animal allergen-free nutritive medium to produce F. duncaniae A2-165. Selecting nutritionally suitable YBNs and combining these with other key nutrients are important steps for optimizing production of NGP with high yields and lower cost.

			Action	DRS
	ACOP02.dat.gz	Other
	ACOP02.fasta.gz	Fasta.gz
	ACOP02.master.dat	Other
	SRR036249.fastq.gz	Fastqsanger.gz
	SRR036249_1.fastq.gz	Fastqsanger.gz

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Faecalibacterium duncaniae strain:A2-165

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