Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice
Transplanting Fecal Virus-Like Particles Reduces High-Fat Diet-Induced Small Intestinal Bacterial Overgrowth in Mice
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DOI：
10.3389/fcimb.2019.00348
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发表时间：
2019-10-15
影响因子：
5.7
通讯作者：
Lin, Henry C.
中科院分区：
文献类型：
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作者：
Lin, Derek M.;Koskella, Britt;Lin, Henry C.
粪便微生物区系移植(FMT)是治疗艰难梭菌感染的一种有效手段。对于与生物失调有关的其他形式的人类疾病，FMT的效果较差。粪便微生物群含有高密度的病毒样颗粒(VLP)，其中高达90%是噬菌体，被认为对调节肠道细菌种群有作用。我们假设，在小肠细菌过度生长(SIBO)的反生菌环境中，移植含有噬菌体的粪便VLP组分可能会降低细菌密度。在一项使用粪便移植的实验中，我们比较了粪便VLP部分(去除细菌)和“完整”FMT(细菌完整)对回肠微生物群的影响。受试者要么接受为期30天的高脂饮食(HFD)治疗，作为生物失调的模型，以诱发SIBO，要么接受标准饮食(SD)。我们观察到，将供者的粪便VLP移植到HFD上足以改变回肠微生物区系，但这种影响取决于受者的饮食。接受HFD治疗的受者回肠细菌密度降低。在接受SD的受者中，回肠微生物群向与HFD相关的成分过渡。在两个受者组中，单独移植粪便VLP部分产生的结果与整个FMT相同。两种处理都没有改变抗菌肽的表达。这些发现证明了VLP的潜在作用，可能是噬菌体，在营养不良期间改变肠道微生物群。
Fecal microbiota transplantation (FMT) is an effective tool for treating Clostridium difficile infection in the setting of dysbiosis of the intestinal microbiome. FMT for other forms of human disorders linked to dysbiosis have been less effective. The fecal microbiota contains a high density of virus-like particles (VLP), up to 90% of which are bacteriophages, thought to have a role in regulating gut bacterial populations. We hypothesized that transplantation of the phage-containing fecal VLP fraction may reduce bacterial density in the dysbiotic setting of small intestinal bacterial overgrowth (SIBO). In an experiment using fecal transplantation, we compared the effect of the fecal VLP fraction (bacteria removed) against "Whole" FMT (bacteria intact) on the ileal microbiome. Recipients were either treated with a 30-day high-fat diet (HFD) as a model of dysbiosis to induce SIBO or were on a standard diet (SD). We observed that transplantation of fecal VLPs from donors on a HFD was sufficient to alter the ileal microbiota, but the effect was dependent on diet of the recipient. In recipients on a HFD, ileal bacterial density was reduced. In recipients on a SD, the ileal microbiome transitioned toward the composition associated with a HFD. In both recipient groups, transplantation of fecal VLP fraction alone produced the same outcome as whole FMT. Neither treatment altered expression of antimicrobial peptides. These findings demonstrated a potential role of VLPs, likely phages, for modifying the gut microbiome during dysbiosis.