Bacterial microcompartments and energy metabolism drive gut colonization by Bilophila wadsworthia

Lizbeth Sayavedra (), Muhammad Yasir, Andrew Goldson, Arlaine Brion, Gwenaelle Le Gall, Mar Moreno-Gonzalez, Annalisa Altera, Michael D. Paxhia, Martin Warren, George M. Savva, A. Keith Turner, Naiara Beraza and Arjan Narbad
Additional contact information
Lizbeth Sayavedra: Norwich Research Park
Muhammad Yasir: Norwich Research Park
Andrew Goldson: Norwich Research Park
Arlaine Brion: Norwich Research Park
Gwenaelle Le Gall: Norwich Research Park
Mar Moreno-Gonzalez: Norwich Research Park
Annalisa Altera: Norwich Research Park
Michael D. Paxhia: Norwich Research Park
Martin Warren: Norwich Research Park
George M. Savva: Norwich Research Park
A. Keith Turner: Norwich Research Park
Naiara Beraza: Norwich Research Park
Arjan Narbad: Norwich Research Park

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60180-y

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