Abstract
There is an urgent need for sustainable protein sources to meet rising global nutritional demands. Here, we show that a commercially scalable microbial lysate from Methylococcus capsulatus Bath (McB), used as a dietary protein, orchestrates host-diet-microbe interactions that protect against gastrointestinal inflammation. McB administration rapidly reshapes the gut microbiota and upregulates microbial fermentation pathways, while robustly increasing peripherally induced regulatory T cells (pTregs) across intestinal regions, independent of the microbiota. In contrast, McB-driven induction of tolerogenic Th17 cells requires a functional microbiota with intact fermentation capacity. In models of mucositis and colitis, McB preserves villus architecture, restores mucosal …
Abstract
There is an urgent need for sustainable protein sources to meet rising global nutritional demands. Here, we show that a commercially scalable microbial lysate from Methylococcus capsulatus Bath (McB), used as a dietary protein, orchestrates host-diet-microbe interactions that protect against gastrointestinal inflammation. McB administration rapidly reshapes the gut microbiota and upregulates microbial fermentation pathways, while robustly increasing peripherally induced regulatory T cells (pTregs) across intestinal regions, independent of the microbiota. In contrast, McB-driven induction of tolerogenic Th17 cells requires a functional microbiota with intact fermentation capacity. In models of mucositis and colitis, McB preserves villus architecture, restores mucosal integrity, and reduces disease severity. Mechanistically, these effects depend on microbial fermentation and functional GLP-2 receptor signalling, yet are independent of endogenous GLP-2 secretion, indicating a fermentation-driven molecular mimicry of GLP-2R activation. Collectively, our findings position microbial lysates as a sustainable nutritional strategy that improves gastrointestinal health through defined immune and microbial pathways.
Data availability
Shotgun sequencing data are uploaded to a public repository with study BioProject Accession number: PRJNA1390501 and the following link: https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1390501. All non-omics datasets included in the current study are available in the figshare repository https://doi.org/10.6084/m9.figshare.30911216. Additionally, all data in this manuscript are available from the corresponding author.
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Acknowledgements
This work was primarily funded by an Excellence Emerging Investigator grant (NNF21OC0066931) issued to BAHJ by Novo Nordisk Foundation, and partly by a grant from the Louis Hansen Fonden (24-2B-16713), issued to S.K.Y.J. Calysta provided the Feedkind® material. BSYC is supported by the BRIDGE–Translational Excellence Program, funded by the Novo Nordisk Foundation (NNF20SA0064340) and by a postdoctoral fellowship from the Fonds de recherche du Québec–Santé (FRQS). The funding bodies had no share in data integration and presentation. Illustrations and schematics were generated via Biorender.com. Furthermore, we want to extend our gratitude to the Core Facility for Integrated Microscopy at the Faculty of Health and Medical Sciences, University of Copenhagen, as well as the members of UCPH Histolab–Associate Professor Jens Brings Jacobsen, Biomedical Laboratory Technologists Bente Stærgaard and Heidi Paulsen, and Associate Professor Steen Seier Poulsen for their valuable support with histological processing and imaging. We would also like to thank the Core Facility for Flow Cytometry and Single Cell Analysis, Faculty of Health and Medical Sciences, University of Copenhagen, for inputs regarding flow cytometry analysis. We gratefully acknowledge Calysta (UK) Ltd. for providing access to commercial McB lysates (Feedkind ®). We want to express our sincere gratitude to Staff Scientist Si Brask Sonne for invaluable help and instruction in the laboratory, and likewise Laboratory Scientists Lene Brus Albæk and Anette Bjerregaard for instrumental assistance with radioimmunoassays and genotyping the GLP-2R and GLP-1R mice. Finally, a thank to Isabella Paul and Cecilie Anastacia Stokkeby Koch for their help, input, and discussions during their traineeship.
Author information
Author notes
These authors contributed equally: Sune K. Yang-Jensen, Béatrice S.-Y. Choi.
Authors and Affiliations
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Sune K. Yang-Jensen, Béatrice S.-Y. Choi, Nora S. Nägele, Simone I. Pærregaard, Kobe Neven, Vytautas Savickas, Nazuk Gupta, Ida M. Modvig, Hannelouise Kissow, Jens J. Holst, Bolette Hartmann & Benjamin A. H. Jensen 1.
Cmbio A/S, Copenhagen, Denmark
Jacob B. Holm 1.
Department of Biology, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
Karsten Kristiansen 1.
The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Jens J. Holst
Authors
- Sune K. Yang-Jensen
- Béatrice S.-Y. Choi
- Nora S. Nägele
- Simone I. Pærregaard
- Kobe Neven
- Vytautas Savickas
- Nazuk Gupta
- Ida M. Modvig
- Jacob B. Holm
- Karsten Kristiansen
- Hannelouise Kissow
- Jens J. Holst
- Bolette Hartmann
- Benjamin A. H. Jensen
Contributions
Study design: S.K.Y.J., B.S.Y.C., S.I.P., and B.A.H.J. S.K.Y.J., B.S.Y.C., N.S.N., K.N., V.S., N.G., I.M.M., and S.I.P., performed experiments. J.B.H. and K.K. were responsible for metagenomic sequencing and subsequent analyses with S.K.Y.J. and B.A.H.J. H.K., J.J.H., and B.H. were involved in breeding GLP-1R and GLP-2R mice, 5-FU experiments, and gut hormone measurements. S.K.Y.J. wrote the first manuscript draft, revised together with B.S.Y.C., and finalized it with B.A.H.J. All authors contributed significantly to the manuscript and approved the final version.
Corresponding author
Correspondence to Benjamin A. H. Jensen.
Ethics declarations
Competing interests
B.A.H.J., J.B.H., and K.K. are co-inventors of an issued patent (US and EU) related to McB and gut dysbiosis. B.A.H.J., S.K.Y.J., and B.S.Y.C. are co-inventors of a patent application related to McB’s potential in treating or preventing gastrointestinal barrier dysfunction. The remaining authors declare that there are no conflicts of interest.
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Yang-Jensen, S.K., Choi, B.SY., Nägele, N.S. et al. Microbial activation of the GLP-2R mitigates gastrointestinal inflammation. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68551-9
Received: 01 July 2025
Accepted: 06 January 2026
Published: 15 January 2026
DOI: https://doi.org/10.1038/s41467-026-68551-9