Food Science, University of Copenhagen, Frederiksberg, Denmark
Veterinary and Animal Sciences, University of Copenhagen, Frederiksberg, Denmark.
Gut. 2020 Dec;69(12):2122-2130. doi: 10.1136/gutjnl-2019-320005. Epub 2020 Mar 12.
Development of obesity and type 2 diabetes (T2D) are associated with gut microbiota (GM) changes. The gut viral community is predominated by bacteriophages (phages), which are viruses that attack bacteria in a host-specific manner. The antagonistic behaviour of phages has the potential to alter the GM. As a proof-of-concept, we demonstrate the efficacy of faecal virome transplantation (FVT) from lean donors for shifting the phenotype of obese mice into closer resemblance of lean mice.
The FVT consisted of viromes with distinct profiles extracted from the caecal content of mice from different vendors that were fed a low-fat (LF) diet for 14 weeks. Male C57BL/6NTac mice were divided into five groups: LF (as diet control), high-fat (HF) diet, HF+ampicillin (Amp), HF+Amp+FVT and HF+FVT. At weeks 6 and 7 of the study, the HF+FVT and HF+Amp+FVT mice were treated with FVT by oral gavage. The Amp groups were treated with Amp 24 hours prior to first FVT treatment.
Six weeks after first FVT, the HF+FVT mice showed a significant decrease in weight gain compared with the HF group. Further, glucose tolerance was comparable between the LF and HF+FVT mice, while the other HF groups all had impaired glucose tolerance. These observations were supported by significant shifts in GM composition, blood plasma metabolome and expression levels of genes associated with obesity and T2D development.
Transfer of caecal viral communities from mice with a lean phenotype into mice with an obese phenotype led to reduced weight gain and normalised blood glucose parameters relative to lean mice. We hypothesise that this effect is mediated via FVT-induced GM changes.
肥胖和 2 型糖尿病（T2D）的发展与肠道微生物群（GM）的变化有关。肠道病毒群落主要由噬菌体（phages）组成，噬菌体是一种以宿主特异性方式攻击细菌的病毒。噬菌体的拮抗行为有可能改变 GM。作为概念验证，我们证明了从瘦供体进行粪便病毒组移植（FVT）的有效性，可将肥胖小鼠的表型转变为更接近瘦小鼠的表型。
FVT 由从来自不同供应商的低脂（LF）饮食喂养 14 周的小鼠盲肠内容物中提取的具有不同特征的病毒组组成。雄性 C57BL/6NTac 小鼠分为五组：LF（作为饮食对照）、高脂肪（HF）饮食、HF+氨苄青霉素（Amp）、HF+Amp+FVT 和 HF+FVT。在研究的第 6 和第 7 周，HF+FVT 和 HF+Amp+FVT 组通过口服灌胃接受 FVT 治疗。Amp 组在首次 FVT 治疗前 24 小时接受 Amp 治疗。
首次 FVT 后 6 周，HF+FVT 小鼠的体重增加明显低于 HF 组。此外，LF 和 HF+FVT 小鼠的葡萄糖耐量相当，而其他 HF 组的葡萄糖耐量均受损。这些观察结果得到了 GM 组成、血浆代谢组和与肥胖和 T2D 发展相关的基因表达水平的显著变化的支持。
将具有瘦表型的小鼠的盲肠病毒群落转移到肥胖表型的小鼠中，可导致体重增加减少，血糖参数正常化，与瘦小鼠相比。我们假设这种效果是通过 FVT 诱导的 GM 变化介导的。
