Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice. / Mao, Xiaotian; Larsen, Sabina Birgitte; Zachariassen, Line Sidsel Fisker; Brunse, Anders; Adamberg, Signe; Mejia, Josue Leonardo Castro; Larsen, Frej; Adamberg, Kaarel; Nielsen, Dennis Sandris; Hansen, Axel Kornerup; Hansen, Camilla Hartmann Friis; Rasmussen, Torben Sølbeck.
I: Nature Communications, Bind 15, 4704, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Transfer of modified gut viromes improves symptoms associated with metabolic syndrome in obese male mice
AU - Mao, Xiaotian
AU - Larsen, Sabina Birgitte
AU - Zachariassen, Line Sidsel Fisker
AU - Brunse, Anders
AU - Adamberg, Signe
AU - Mejia, Josue Leonardo Castro
AU - Larsen, Frej
AU - Adamberg, Kaarel
AU - Nielsen, Dennis Sandris
AU - Hansen, Axel Kornerup
AU - Hansen, Camilla Hartmann Friis
AU - Rasmussen, Torben Sølbeck
N1 - Publisher Copyright: © 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-024-49152-w
DO - 10.1038/s41467-024-49152-w
M3 - Journal article
C2 - 38830845
AN - SCOPUS:85195006914
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 4704
ER -
ID: 394532695