Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.
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微生物群转移疗法改变肠道生态系统并改善胃肠道和自闭症症状：一项开放标签研究。
DOI：
10.1186/s40168-016-0225-7
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发表时间：
2017-01-23
期刊：
影响因子：
15.5
通讯作者：
Krajmalnik-Brown R
中科院分区：
文献类型：
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作者：
Kang DW;Adams JB;Gregory AC;Borody T;Chittick L;Fasano A;Khoruts A;Geis E;Maldonado J;McDonough-Means S;Pollard EL;Roux S;Sadowsky MJ;Lipson KS;Sullivan MB;Caporaso JG;Krajmalnik-Brown R
自闭症谱系障碍（ASD）是一种复杂的神经生物学障碍，损害社会互动和沟通，并导致行为，兴趣和活动的限制，重复和刻板模式。这些疾病的原因仍然知之甚少，但肠道微生物群，人类肠道中的1013种细菌，已经被牵连，因为ASD儿童经常遭受与ASD严重程度相关的胃肠道（GI）问题。先前的几项研究报告了ASD儿童的肠道细菌异常。肠道微生物组-ASD连接已在ASD小鼠模型中进行了测试，其中微生物组与异常代谢物和行为有机械联系。同样，一项针对ASD儿童的研究发现，口服非吸收性抗生素治疗可以改善GI和ASD症状，尽管是暂时的。在这里，一项小型开放标签临床试验评估了微生物群转移疗法（MTT）对18名ASD诊断儿童的肠道微生物群组成以及GI和ASD症状的影响。MTT包括2周的抗生素治疗，肠道清洁，然后使用高初始剂量进行延长的粪便微生物群移植（FMT），然后每天和较低的维持剂量持续7-8周。胃肠道症状评定量表显示，治疗结束时GI症状减少约80%，包括便秘、腹泻、消化不良和腹痛症状的显著改善。治疗后持续改善8周。同样，临床评估显示行为ASD症状显著改善，并在治疗结束后8周保持改善。细菌和噬菌体深度测序分析显示，供体微生物群成功部分植入，肠道环境发生了有益的变化。具体而言，在MTT后，总体细菌多样性和双歧杆菌属、普雷沃氏菌属和脱硫弧菌属等分类群的丰度增加，并且这些变化在治疗停止后持续（随后8周）。因此，这种探索性的、持续时间延长的治疗方案似乎是改变肠道微生物组和病毒组并改善ASD的GI和行为症状的有希望的方法。GI症状，ASD症状和微生物组的改善在治疗结束后持续至少8周，这表明了长期影响。该试验已在ClinicalTrials.gov上注册，注册号为NCT 02504554。本文的在线版本（doi：10.1186/s40168-016-0225-7）包含补充材料，可供授权用户使用。
Autism spectrum disorders (ASD) are complex neurobiological disorders that impair social interactions and communication and lead to restricted, repetitive, and stereotyped patterns of behavior, interests, and activities. The causes of these disorders remain poorly understood, but gut microbiota, the 1013 bacteria in the human intestines, have been implicated because children with ASD often suffer gastrointestinal (GI) problems that correlate with ASD severity. Several previous studies have reported abnormal gut bacteria in children with ASD. The gut microbiome-ASD connection has been tested in a mouse model of ASD, where the microbiome was mechanistically linked to abnormal metabolites and behavior. Similarly, a study of children with ASD found that oral non-absorbable antibiotic treatment improved GI and ASD symptoms, albeit temporarily. Here, a small open-label clinical trial evaluated the impact of Microbiota Transfer Therapy (MTT) on gut microbiota composition and GI and ASD symptoms of 18 ASD-diagnosed children. MTT involved a 2-week antibiotic treatment, a bowel cleanse, and then an extended fecal microbiota transplant (FMT) using a high initial dose followed by daily and lower maintenance doses for 7–8 weeks. The Gastrointestinal Symptom Rating Scale revealed an approximately 80% reduction of GI symptoms at the end of treatment, including significant improvements in symptoms of constipation, diarrhea, indigestion, and abdominal pain. Improvements persisted 8 weeks after treatment. Similarly, clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended. Bacterial and phagedeep sequencing analyses revealed successful partial engraftment of donor microbiota and beneficial changes in the gut environment. Specifically, overall bacterial diversity and the abundance of Bifidobacterium, Prevotella, and Desulfovibrio among other taxa increased following MTT, and these changes persisted after treatment stopped (followed for 8 weeks). This exploratory, extended-duration treatment protocol thus appears to be a promising approach to alter the gut microbiome and virome and improve GI and behavioral symptoms of ASD. Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact. This trial was registered on the ClinicalTrials.gov, with the registration number NCT02504554 The online version of this article (doi:10.1186/s40168-016-0225-7) contains supplementary material, which is available to authorized users.