Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice
Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice
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DOI：
10.1126/scitranslmed.aaf6397
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发表时间：
2017-03-01
影响因子：
17.1
通讯作者：
Bercik, Premysl
中科院分区：
文献类型：
--
作者：
De Palma, Giada;Lynch, Michael D. J.;Bercik, Premysl
肠易激综合征（IBS）是一种以肠道功能改变为特征的常见疾病，通常伴有共病焦虑。虽然肠道微生物群的变化已被记录，但其与IBS临床表现的相关性尚不清楚。为了评估肠道细菌在IBS中的功能作用，我们用来自健康对照个体或患有腹泻的IBS患者（IBS-D）的粪便微生物群定殖无菌小鼠，有或没有焦虑，并监测移植小鼠的肠道功能和行为。受体小鼠中的微生物群谱根据人类供体的微生物群谱聚类。接受IBS-D粪便微生物群的小鼠显示出与接受健康对照粪便微生物群的小鼠在分类学上相似的微生物组成。然而，IBS-D小鼠表现出不同的血清代谢谱。接受IBS-D粪便微生物群而不是健康对照粪便微生物群的小鼠表现出更快的胃肠道传输、肠屏障功能障碍、先天免疫激活和焦虑样行为。这些结果表明，肠道微生物群可能有助于IBS-D的肠道和行为表现，并表明微生物群导向疗法在IBS患者中的潜在价值。
Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mice with the fecal microbiota from healthy control individuals or IBS patients with diarrhea (IBS-D), with or without anxiety, and monitored gut function and behavior in the transplanted mice. Microbiota profiles in recipient mice clustered according to the microbiota profiles of the human donors. Mice receiving the IBS-D fecal microbiota showed a taxonomically similar microbial composition to that of mice receiving the healthy control fecal microbiota. However, IBS-D mice showed different serum metabolomic profiles. Mice receiving the IBS-D fecal microbiota, but not the healthy control fecal microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation, and anxiety-like behavior. These results indicate the potential of the gut microbiota to contribute to both intestinal and behavioral manifestations of IBS-D and suggest the potential value of microbiota-directed therapies in IBS patients.