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Design of a proteolytic module for improved metabolic modeling of Bacteroides caccae

hal.structure.identifierMICrobiologie de l'ALImentation au Service de la Santé [MICALIS]
hal.structure.identifierBiomathematica
dc.contributor.authorPAULAY, Amandine
hal.structure.identifierBiomathematica
dc.contributor.authorGRIMAUD, Ghjuvan
hal.structure.identifierMICrobiologie de l'ALImentation au Service de la Santé [MICALIS]
dc.contributor.authorCABALLERO, Raphaël
hal.structure.identifierMathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] [MaIAGE]
hal.structure.identifierDynamiques de populations multi-échelles pour des systèmes physiologiques / MUltiSCAle population dynamics for physiological systems [MUSCA]
dc.contributor.authorLAROCHE, Béatrice
hal.structure.identifierMICrobiologie de l'ALImentation au Service de la Santé [MICALIS]
hal.structure.identifierPendulum Therapeutics [San Francisco]
dc.contributor.authorLECLERC, Marion
hal.structure.identifierBiodiversité, Gènes & Communautés [BioGeCo]
hal.structure.identifierMathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] [MaIAGE]
hal.structure.identifierPleiade, from patterns to models in computational biodiversity and biotechnology [PLEIADE]
dc.contributor.authorLABARTHE, Simon
hal.structure.identifierMICrobiologie de l'ALImentation au Service de la Santé [MICALIS]
hal.structure.identifierInstitut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement [INRAE]
dc.contributor.authorMAGUIN, Emmanuelle
dc.date.issued2024-03-22
dc.identifier.issn2379-5077
dc.description.abstractEnThe gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on Bacteroides caccae , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that B. caccae possesses a set of 156 proteases with putative intracellular and extracellular localization and allowed to identify amino acid transporters and metabolic pathways. We developed a fully curated genome-scale metabolic model of B. caccae that incorporated its proteolytic activity and simulated its growth and production of fermentation-related metabolites in response to the different growth media. We validated the model by comparing the predicted phenotype to experimental data. The model accurately predicted B. caccae ’s growth and metabolite production ( R 2 = 0.92 for the training set and R 2 = 0.89 for the validation set). We found that accounting for both ATP consumption related to proteolysis, and whey protein accessibility is necessary for accurate predictions of metabolites production. These results provide insights into B. caccae ’s adaptation to a high-protein diet and its ability to utilize proteins as a source of nutrition. The proposed model provides a useful tool for understanding the feeding mechanism of B. caccae in the gut microbiome. IMPORTANCE Microbial proteolysis is understudied despite the availability of dietary proteins for the gut microbiota. Here, the proteolytic potential of the gut symbiont Bacteroides caccae was analyzed for the first time using pan-genomics. This sketches a well-equipped bacteria for protein breakdown, capable of producing 156 different proteases with a broad spectrum of cleavage targets. This functional potential was confirmed by the enhancement of growth and metabolic activities at high protein levels. Proteolysis was included in a B. caccae metabolic model which was fitted with the experiments and validated on external data. This model pinpoints the links between protein availability and short-chain fatty acids production, and the importance for B. caccae to gain access to glutamate and asparagine to promote growth. This integrated approach can be generalized to other symbionts and upscaled to complex microbiota to get insights into the ecological impact of proteins on the gut microbiota.
dc.description.sponsorshipLES CELLULES MAIT A L'INTERFACE ENTRE INFLAMMATION ET MICROBIOTE DANS LA DYSFONCTION METABOLIQUE ET LA STEATOSE HEPATIQUE - ANR-19-CE14-0041
dc.description.sponsorshipInhibition de Trypsin-3: une nouvelle cible thérapeutique - ANR-18-CE18-0019
dc.language.isoen
dc.rights.urihttp://creativecommons.org/licenses/by/
dc.subject.enmicrobiota
dc.subject.enflux balance analysis
dc.subject.enproteolysis
dc.subject.enproteases
dc.subject.enmetabolic modeling
dc.subject.enholobiont
dc.title.enDesign of a proteolytic module for improved metabolic modeling of Bacteroides caccae
dc.typeArticle de revue
dc.identifier.doi10.1128/msystems.00153-24
dc.subject.halSciences du Vivant [q-bio]
dc.description.sponsorshipEuropeHarnessing the microbial potential of fermented food for healthy & sustainable food systems
bordeaux.journalmSystems
bordeaux.volume9
bordeaux.issue4
bordeaux.peerReviewedoui
hal.identifierhal-04540116
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-04540116v1
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=mSystems&rft.date=2024-03-22&rft.volume=9&rft.issue=4&rft.eissn=2379-5077&rft.issn=2379-5077&rft.au=PAULAY,%20Amandine&GRIMAUD,%20Ghjuvan&CABALLERO,%20Rapha%C3%ABl&LAROCHE,%20B%C3%A9atrice&LECLERC,%20Marion&rft.genre=article


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