Genome-Scale Model and Omics Analysis of Metabolic Capacities of Akkermansia muciniphila Reveal a Preferential Mucin-Degrading Lifestyle
Open accessAbstract
The composition and activity of the microbiota in the human gastrointestinal tract are primarily shaped by nutrients derived from either food or the host. Bacteria colonizing the mucus layer have evolved to use mucin as a carbon and energy source. One of the members of the mucosa-associated microbiota is Akkermansia muciniphila , which is capable of producing an extensive repertoire of mucin-degrading enzymes. To further study the substrate utilization abilities of A. muciniphila , we constructed a genome-scale metabolic model to test amino acid auxotrophy, vitamin biosynthesis, and sugar-degrading capacities. The model-supported predictions were validated by in vitro experiments, which showed A. muciniphila to be able to utilize the mucin-derived monosaccharides fucose, galactose, and N -acetylglucosamine. Growth was also observed on N -acetylgalactosamine, even though the metabolic model did not predict this. The uptake of these sugars, as well as the nonmucin sugar glucose, was enhanced in the presence of mucin, indicating that additional mucin-derived components are needed for optimal growth. An analysis of whole-transcriptome sequencing (RNA-Seq) comparing the gene expression of A. muciniphila grown on mucin with that of the same bacterium grown on glucose confirmed the activity of the genes involved in mucin degradation and revealed most of these to be upregulated in the presence of mucin. The transcriptional response was confirmed by a proteome analysis, altogether revealing a hierarchy in the use of sugars and reflecting the adaptation of A. muciniphila to the mucosal environment. In conclusion, these findings provide molecular insights into the lifestyle of A. muciniphila and further confirm its role as a mucin specialist in the gut. IMPORTANCE Akkermansia muciniphila is among the most abundant mucosal bacteria in humans and in a wide range of other animals. Recently, A. muciniphila has attracted considerable attention because of its capacity to protect against diet-induced obesity in mouse models. However, the physiology of A. muciniphila has not been studied in detail. Hence, we constructed a genome-scale model and describe its validation by transcriptomic and proteomic approaches on bacterial cells grown on mucus and glucose, a nonmucus sugar. The results provide detailed molecular insight into the mucus-degrading lifestyle of A. muciniphila and further confirm the role of this mucin specialist in producing propionate and acetate under conditions of the intestinal tract.
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Akkermansia muciniphila has been experimentally shown to use mucin-derived monosaccharides, including fucose, galactose, N-acetylglucosamine, and N-acetylgalactosamine, supporting its adaptation to the mucus layer.
“Akkermansia muciniphila has been experimentally shown to use mucin-derived monosaccharides, including fucose, galactose, N-acetylglucosamine, and N-acetylgalactosamine, supporting its adaptation to the mucus layer. 35”
In Akkermansia, adhesion to the mucus layer is relevant because access to mucins supports its ecological role.
“In Akkermansia , adhesion to the mucus layer is relevant because access to mucins supports its ecological role. 24,35”
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- Authors
- Ottman, N., Davids, M., Suarez-Diez, M., Boeren, S., Schaap, P. J., Martins dos Santos, V. A. P., Smidt, H., Belzer, C., & de Vos, W. M.
- Affiliations
- Wageningen University & Research (NL)
- Laboratory of Systems and Synthetic Biology, Wageningen University, Wageningen, the Netherlands
- Laboratory of Microbiology, Wageningen University, Wageningen, the Netherlands
- Venue
- Applied and Environmental Microbiology
- Publisher
- American Society for Microbiology
- Published
- 2017-09-15
- Volume
- 83
- Issue
- 18
- ISSN
- 0099-2240 (ISSN-L)
- 1098-5336
- PMC
- PMC5583483
- OpenAlex
- W2729285740
- Cited by
- 269
- References
- 11
- Citations by year
- 2026: 36 · 2025: 36 · 2024: 37 · 2023: 34 · 2022: 39 · 2021: 35 · 2020: 23 · 2019: 15 · 2018: 11 · 2017: 2
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Applied and Environmental Microbiology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, cc-by)
- Socio-Environmental Systems Modeling (acceptedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (024.002.002, Spinoza)
- Suomen Akatemia (141130)
- EC | FP7 | FP7 Ideas: European Research Council (250172)
- EC | FP7 | FP7 People: Marie-Curie Actions (215553-2)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- Akkermansia muciniphila, mucin degradation, genome-scale metabolic models, mucosa-associated microbiota, amino acid auxotrophy, vitamin biosynthesis, sugar utilization, fucose, galactose, N-acetylglucosamine, N-acetylgalactosamine, gene expression, proteome, bacterial lifestyle, propionate, acetate, gut microbiota
- MeSH terms
- Animals, Bacterial Proteins, Glucose, Intestinal Mucosa, Intestines, Mucins, Swine, Genome, Bacterial, Proteomics, Verrucomicrobia
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