肠易激综合征患者粪菌移植至受体小鼠,改变其肠道功能和行为
Title:
Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice
DOI:
10.1126/scitranslmed.aaf6397
Abstract:
Connecting the gut-brain axis: Irritable bowel syndrome (IBS), the most common gastrointestinal disorder worldwide, is characterized by abdominal pain and altered gut function and often is accompanied by anxiety. An association between intestinal dysbiosis and IBS has been reported, but the functional relevance remains unknown. De Palma and colleagues colonized germ-free mice with fecal microbiota from healthy controls or IBS patients with diarrhea (IBS-D) who did or did not have anxiety. They demonstrated that transplantation of fecal microbiota from patients with IBS-D and anxiety resulted in altered gut function and behavior in mouse recipients, including faster gastrointestinal transit, low-grade inflammation, and anxiety-like behavior. Abstract: 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.
All Authors:
Giada De Palma,Michael D J Lynch,Jun Lu,Vi T Dang,Yikang Deng,Jennifer Jury,Genevieve Umeh,Pedro M Miranda,Marc Pigrau Pastor,Sacha Sidani,Maria Ines Pinto-Sanchez,Vivek Philip,Peter G McLean,Moreno-Gabriel Hagelsieb,Michael G Surette,Gabriela E Bergonzelli,Elena F Verdu,Philip Britz-McKibbin,Josh D Neufeld,Stephen M Collins,Premysl Bercik
First Authors:
Giada De Palma
Correspondence:
Premysl Bercik
内容要点:
肠易激综合征(IBS)患者常常伴有焦虑,肠道菌群也发生改变,研究者为此在无菌小鼠中移植有或无焦虑症状的腹泻IBS(IBS-D)病人的粪便菌群,以判断菌群的作用。 受体小鼠中菌群的特征取决于人类供体的菌群特征。尽管接受了IBS-D菌群的小鼠与接受健康对照菌群小鼠展现出分类学上类似的微生物组成,但IBS-D小鼠的血清代谢特征不同。 IBS-D小鼠展现出更快的胃肠道通过、肠屏障功能障碍、先天免疫激活和焦虑样行为。
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