Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice

Xiaotian Mao, Sabina Birgitte Larsen, Line Sidsel Fisker Zachariassen, Anders Brunse, Signe Adamberg, Josue Leonardo Castro Mejia, Frej Larsen, Kaarel Adamberg, Dennis Sandris Nielsen, Axel Kornerup Hansen, Camilla Hartmann Friis Hansen and Torben Sølbeck Rasmussen ()
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Xiaotian Mao: University of Copenhagen
Sabina Birgitte Larsen: University of Copenhagen
Line Sidsel Fisker Zachariassen: University of Copenhagen
Anders Brunse: University of Copenhagen
Signe Adamberg: Tallinn University of Technology
Josue Leonardo Castro Mejia: University of Copenhagen
Frej Larsen: University of Copenhagen
Kaarel Adamberg: Tallinn University of Technology
Dennis Sandris Nielsen: University of Copenhagen
Axel Kornerup Hansen: University of Copenhagen
Camilla Hartmann Friis Hansen: University of Copenhagen
Torben Sølbeck Rasmussen: University of Copenhagen

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Metabolic syndrome encompasses amongst other conditions like obesity and type-2 diabetes and is associated with gut microbiome (GM) dysbiosis. Fecal microbiota transplantation (FMT) has been explored to treat metabolic syndrome by restoring the GM; however, concerns on accidentally transferring pathogenic microbes remain. As a safer alternative, fecal virome transplantation (FVT, sterile-filtrated feces) has the advantage over FMT in that mainly bacteriophages are transferred. FVT from lean male donors have shown promise in alleviating the metabolic effects of high-fat diet in a preclinical mouse study. However, FVT still carries the risk of eukaryotic viral infections. To address this, recently developed methods are applied for removing or inactivating eukaryotic viruses in the viral component of FVT. Modified FVTs are compared with unmodified FVT and saline in a diet-induced obesity model on male C57BL/6 N mice. Contrasted with obese control, mice administered a modified FVT (nearly depleted for eukaryotic viruses) exhibits enhanced blood glucose clearance but not weight loss. The unmodified FVT improves liver pathology and reduces the proportions of immune cells in the adipose tissue with a non-uniform response. GM analysis suggests that bacteriophage-mediated GM modulation influences outcomes. Optimizing these approaches could lead to the development of safe bacteriophage-based therapies targeting metabolic syndrome through GM restoration.

Date: 2024
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DOI: 10.1038/s41467-024-49152-w

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