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ToolsSayavedra, Lizbeth, Yasir, Muhammad, Goldson, Andrew, Brion, Arlaine, Le Gall, Gwenaelle, Moreno-Gonzalez, Mar, Altera, Annalisa, Paxhia, Michael D., Warren, Martin, Savva, George M., Turner, A. Keith, Beraza, Naiara and Narbad, Arjan (2025) Bacterial microcompartments and energy metabolism drive gut colonization by Bilophila wadsworthia. Nature Communications, 16. ISSN 2041-1723
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Abstract
High-fat diets reshape gut microbiota composition and promote the expansion of Bilophila wadsworthia, a sulfidogenic bacterium linked to inflammation and gut barrier dysfunction. The genetic basis for its colonisation and physiological effects remain poorly understood. Here, we show that B. wadsworthia colonises the gut of germ-free male mice fed a high-fat diet by relying on genes involved in microcompartment formation and anaerobic energy metabolism. Using genome-wide transposon mutagenesis, metatranscriptomics and metabolomics, we identify 34 genes essential for gut colonisation, including two clusters encoding a bacterial microcompartment (BMC),and a NADH dehydrogenase (hdrABC-flxABCD) complex. These systems enable B. wadsworthia to metabolise taurine and isethionate, producing H2S, acetate, and ethanol. We further demonstrate that B. wadsworthia can produce and consume ethanol depending on the available electron donors. While B.wadsworthia reached higher abundance and H₂S production in the absence of the simplified microbiota, its co-colonisation with the defined microbial consortium exacerbated host effects, including increased gut permeability, slightly elevated liver ethanol concentrations, and hepatic macrophage infiltration. Our findings reveal how microbial interactions and metabolic flexibility -including using alternative energy sources such as formate- rather than H₂S alone, shape B. wadsworthia’s impact on host physiology, with implications for understanding diet-driven microbiome–host interactions.
| Item Type: | Article |
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| Additional Information: | Data availability statement: TraDIS sequencing data generated in this study have been deposited in the NCBI Sequence Read Archive (SRA) under the project PRJNA1115966 [https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1115966]. Metatranscriptomic sequencing data of the mice caecum are available under project PRJNA1113627 [https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1113627]. The complete genome of Bilophila wadsworthia QI0013 was submitted under project PRJNA1085689 [https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1085689]. The plasmid pQtnpATnC5mPv2.1 is available from Keith Turner. The E. coli strain MFDPir can be obtained from the Institut Pasteur’s Biological Resources Centre (CRBIP). Source Data underlying all figures and statistical analyses are provided with this paper. Individual-level metadata of the faecal human donor cannot be made available as they are protected by the QIB Colon Model (NCT02653001) ethical approvals. Source data are provided with this paper. Code availability statement: Custom code to create some of the graphs is available at GitHub: github.com/lsayaved/Bilophila archived on Zenodo as: https://doi.org/10.5281/zenodo.15356479. Funding information: This research was funded by the BBSRC Institute Strategic Programme Food Microbiome & Health ISP BB/X011054/1 and its constituent project BBS/E/QU/230001. LS was supported by a BBSRC Discovery Fellowship (BB/Z514445/1). |
| Faculty \ School: | Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Science Faculty of Medicine and Health Sciences > School of Health Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 04 Jun 2025 14:30 |
| Last Modified: | 04 Jun 2025 14:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/99391 |
| DOI: | 10.1038/s41467-025-60180-y |
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