Section of Food Microbiology, Gut Health, and Fermentation, Department of Food Science, University of Copenhagen, Frederiksberg, Denmark.
Section of Preclinical Disease Biology, Department of Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Nat Commun. 2024 Jun 3;15(1):4704. doi: 10.1038/s41467-024-49152-w.
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.
代谢综合征包括肥胖症和 2 型糖尿病等疾病，与肠道微生物组（GM）失调有关。通过恢复 GM，粪便微生物群移植（FMT）已被探索用于治疗代谢综合征；然而，人们仍然担心会意外转移致病微生物。作为一种更安全的选择，粪便病毒群移植（FVT，无菌过滤粪便）在传递物上主要是噬菌体，相对于 FMT 具有优势。来自瘦型雄性供体的 FVT 在一项临床前小鼠研究中显示出有希望减轻高脂肪饮食的代谢影响。然而，FVT 仍存在真核病毒感染的风险。为了解决这个问题，最近开发的方法被应用于去除或失活 FVT 病毒成分中的真核病毒。在雄性 C57BL/6N 小鼠的饮食诱导肥胖模型中，对改良的 FVT 与未改良的 FVT 和生理盐水进行了比较。与肥胖对照组相比，给予改良 FVT（几乎耗尽真核病毒）的小鼠表现出血糖清除增强，但体重未减轻。未改良的 FVT 可改善肝脏病理，并减少脂肪组织中免疫细胞的比例，但反应不均匀。GM 分析表明，噬菌体介导的 GM 调节影响结果。优化这些方法可能会导致通过 GM 恢复开发针对代谢综合征的安全噬菌体为基础的治疗方法。
