Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease
Abstract Background The human gut microbiome performs important functions in human health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids and their subsequent deconjugation and transformation by the gut microbiome. To understand these sy...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40168-019-0689-3 |
| _version_ | 1818041884195422208 |
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| author | Almut Heinken Dmitry A. Ravcheev Federico Baldini Laurent Heirendt Ronan M. T. Fleming Ines Thiele |
| author_facet | Almut Heinken Dmitry A. Ravcheev Federico Baldini Laurent Heirendt Ronan M. T. Fleming Ines Thiele |
| author_sort | Almut Heinken |
| collection | DOAJ |
| description | Abstract Background The human gut microbiome performs important functions in human health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids and their subsequent deconjugation and transformation by the gut microbiome. To understand these system-level host-microbe interactions, a mechanistic, multi-scale computational systems biology approach that integrates the different types of omic data is needed. Here, we use a systematic workflow to computationally model bile acid metabolism in gut microbes and microbial communities. Results Therefore, we first performed a comparative genomic analysis of bile acid deconjugation and biotransformation pathways in 693 human gut microbial genomes and expanded 232 curated genome-scale microbial metabolic reconstructions with the corresponding reactions (available at https://vmh.life). We then predicted the bile acid biotransformation potential of each microbe and in combination with other microbes. We found that each microbe could produce maximally six of the 13 secondary bile acids in silico, while microbial pairs could produce up to 12 bile acids, suggesting bile acid biotransformation being a microbial community task. To investigate the metabolic potential of a given microbiome, publicly available metagenomics data from healthy Western individuals, as well as inflammatory bowel disease patients and healthy controls, were mapped onto the genomes of the reconstructed strains. We constructed for each individual a large-scale personalized microbial community model that takes into account strain-level abundances. Using flux balance analysis, we found considerable variation in the potential to deconjugate and transform primary bile acids between the gut microbiomes of healthy individuals. Moreover, the microbiomes of pediatric inflammatory bowel disease patients were significantly depleted in their bile acid production potential compared with that of controls. The contributions of each strain to overall bile acid production potential across individuals were found to be distinct between inflammatory bowel disease patients and controls. Finally, bottlenecks limiting secondary bile acid production potential were identified in each microbiome model. Conclusions This large-scale modeling approach provides a novel way of analyzing metagenomics data to accelerate our understanding of the metabolic interactions between the host and gut microbiomes in health and diseases states. Our models and tools are freely available to the scientific community. |
| first_indexed | 2024-12-10T08:37:31Z |
| format | Article |
| id | doaj.art-dcf614623d0b44eeaf0e6e3d45e6b03b |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-12-10T08:37:31Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-dcf614623d0b44eeaf0e6e3d45e6b03b2022-12-22T01:55:57ZengBMCMicrobiome2049-26182019-05-017111810.1186/s40168-019-0689-3Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel diseaseAlmut Heinken0Dmitry A. Ravcheev1Federico Baldini2Laurent Heirendt3Ronan M. T. Fleming4Ines Thiele5School of Medicine, National University of Ireland, GalwaySchool of Medicine, National University of Ireland, GalwayLuxembourg Centre for Systems Biomedicine, University of LuxembourgLuxembourg Centre for Systems Biomedicine, University of LuxembourgDivision of Analytical Biosciences, Leiden Academic Centre for Drug Research, Faculty of Science, University of LeidenSchool of Medicine, National University of Ireland, GalwayAbstract Background The human gut microbiome performs important functions in human health and disease. A classic example for host-gut microbial co-metabolism is host biosynthesis of primary bile acids and their subsequent deconjugation and transformation by the gut microbiome. To understand these system-level host-microbe interactions, a mechanistic, multi-scale computational systems biology approach that integrates the different types of omic data is needed. Here, we use a systematic workflow to computationally model bile acid metabolism in gut microbes and microbial communities. Results Therefore, we first performed a comparative genomic analysis of bile acid deconjugation and biotransformation pathways in 693 human gut microbial genomes and expanded 232 curated genome-scale microbial metabolic reconstructions with the corresponding reactions (available at https://vmh.life). We then predicted the bile acid biotransformation potential of each microbe and in combination with other microbes. We found that each microbe could produce maximally six of the 13 secondary bile acids in silico, while microbial pairs could produce up to 12 bile acids, suggesting bile acid biotransformation being a microbial community task. To investigate the metabolic potential of a given microbiome, publicly available metagenomics data from healthy Western individuals, as well as inflammatory bowel disease patients and healthy controls, were mapped onto the genomes of the reconstructed strains. We constructed for each individual a large-scale personalized microbial community model that takes into account strain-level abundances. Using flux balance analysis, we found considerable variation in the potential to deconjugate and transform primary bile acids between the gut microbiomes of healthy individuals. Moreover, the microbiomes of pediatric inflammatory bowel disease patients were significantly depleted in their bile acid production potential compared with that of controls. The contributions of each strain to overall bile acid production potential across individuals were found to be distinct between inflammatory bowel disease patients and controls. Finally, bottlenecks limiting secondary bile acid production potential were identified in each microbiome model. Conclusions This large-scale modeling approach provides a novel way of analyzing metagenomics data to accelerate our understanding of the metabolic interactions between the host and gut microbiomes in health and diseases states. Our models and tools are freely available to the scientific community.http://link.springer.com/article/10.1186/s40168-019-0689-3Gut microbiomeBile acidsHost-microbe interactionsMetabolismGenome-scale reconstructionConstraint-based modeling |
| spellingShingle | Almut Heinken Dmitry A. Ravcheev Federico Baldini Laurent Heirendt Ronan M. T. Fleming Ines Thiele Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease Microbiome Gut microbiome Bile acids Host-microbe interactions Metabolism Genome-scale reconstruction Constraint-based modeling |
| title | Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| title_full | Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| title_fullStr | Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| title_full_unstemmed | Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| title_short | Systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| title_sort | systematic assessment of secondary bile acid metabolism in gut microbes reveals distinct metabolic capabilities in inflammatory bowel disease |
| topic | Gut microbiome Bile acids Host-microbe interactions Metabolism Genome-scale reconstruction Constraint-based modeling |
| url | http://link.springer.com/article/10.1186/s40168-019-0689-3 |
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