Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling

Abstract Although bifidobacteria are widely used as probiotics, their metabolism and physiology remain to be explored in depth. In this work, strain-specific genome-scale metabolic models were developed for two industrially and clinically relevant bifidobacteria, Bifidobacterium animalis subsp. lact...

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Main Authors: Marie Schöpping, Paula Gaspar, Ana Rute Neves, Carl Johan Franzén, Ahmad A. Zeidan
Format: Article
Language:English
Published: Nature Portfolio 2021-12-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-021-00207-4
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author Marie Schöpping
Paula Gaspar
Ana Rute Neves
Carl Johan Franzén
Ahmad A. Zeidan
author_facet Marie Schöpping
Paula Gaspar
Ana Rute Neves
Carl Johan Franzén
Ahmad A. Zeidan
author_sort Marie Schöpping
collection DOAJ
description Abstract Although bifidobacteria are widely used as probiotics, their metabolism and physiology remain to be explored in depth. In this work, strain-specific genome-scale metabolic models were developed for two industrially and clinically relevant bifidobacteria, Bifidobacterium animalis subsp. lactis BB-12® and B. longum subsp. longum BB-46, and subjected to iterative cycles of manual curation and experimental validation. A constraint-based modeling framework was used to probe the metabolic landscape of the strains and identify their essential nutritional requirements. Both strains showed an absolute requirement for pantethine as a precursor for coenzyme A biosynthesis. Menaquinone-4 was found to be essential only for BB-46 growth, whereas nicotinic acid was only required by BB-12®. The model-generated insights were used to formulate a chemically defined medium that supports the growth of both strains to the same extent as a complex culture medium. Carbohydrate utilization profiles predicted by the models were experimentally validated. Furthermore, model predictions were quantitatively validated in the newly formulated medium in lab-scale batch fermentations. The models and the formulated medium represent valuable tools to further explore the metabolism and physiology of the two species, investigate the mechanisms underlying their health-promoting effects and guide the optimization of their industrial production processes.
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spelling doaj.art-ac2fb7f572e14a6ea4afb5d172e624ff2022-12-21T21:43:25ZengNature Portfolionpj Systems Biology and Applications2056-71892021-12-017111510.1038/s41540-021-00207-4Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modelingMarie Schöpping0Paula Gaspar1Ana Rute Neves2Carl Johan Franzén3Ahmad A. Zeidan4Systems Biology, DiscoverySystems Biology, DiscoverySystems Biology, DiscoveryDivision of Industrial Biotechnology, Department of Biology and Biological Engineering, Chalmers University of TechnologySystems Biology, DiscoveryAbstract Although bifidobacteria are widely used as probiotics, their metabolism and physiology remain to be explored in depth. In this work, strain-specific genome-scale metabolic models were developed for two industrially and clinically relevant bifidobacteria, Bifidobacterium animalis subsp. lactis BB-12® and B. longum subsp. longum BB-46, and subjected to iterative cycles of manual curation and experimental validation. A constraint-based modeling framework was used to probe the metabolic landscape of the strains and identify their essential nutritional requirements. Both strains showed an absolute requirement for pantethine as a precursor for coenzyme A biosynthesis. Menaquinone-4 was found to be essential only for BB-46 growth, whereas nicotinic acid was only required by BB-12®. The model-generated insights were used to formulate a chemically defined medium that supports the growth of both strains to the same extent as a complex culture medium. Carbohydrate utilization profiles predicted by the models were experimentally validated. Furthermore, model predictions were quantitatively validated in the newly formulated medium in lab-scale batch fermentations. The models and the formulated medium represent valuable tools to further explore the metabolism and physiology of the two species, investigate the mechanisms underlying their health-promoting effects and guide the optimization of their industrial production processes.https://doi.org/10.1038/s41540-021-00207-4
spellingShingle Marie Schöpping
Paula Gaspar
Ana Rute Neves
Carl Johan Franzén
Ahmad A. Zeidan
Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
npj Systems Biology and Applications
title Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
title_full Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
title_fullStr Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
title_full_unstemmed Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
title_short Identifying the essential nutritional requirements of the probiotic bacteria Bifidobacterium animalis and Bifidobacterium longum through genome-scale modeling
title_sort identifying the essential nutritional requirements of the probiotic bacteria bifidobacterium animalis and bifidobacterium longum through genome scale modeling
url https://doi.org/10.1038/s41540-021-00207-4
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