孤独症谱系障碍（autism spectrum disorder，ASD）是一种广泛神经发育障碍性疾病，其主要特点为言语及社交障碍、兴趣狭窄、重复刻板行为等[1]。近年我国ASD患病率逐年上升，患病率达1% [2]。目前以教育康复训练为主的疗效有限，缺乏更有效的治疗方法。

肠道微生物组已被报道可通过菌群-肠-脑轴参与ASD的发病机制[3]，影响其胃肠道功能和行为[4,5]。因此，以肠道微生物组为靶点治疗/预防孤独症可能是一种新的安全、有效、无副作用的突破点。

2024年9月10日，广州医科大学附属第二医院邓宇虹研究团队在《Frontiers in Nutrition》期刊发表了题为：Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial的研究论文。

该研究表明：BF839可显著改善ASD儿童的异常行为及胃肠道症状，尤其是反映刻板行为的运动能力，小于4岁可能是益生菌干预有效的窗口期；且BF839可促进ASD儿童肠内双歧杆菌生长。

儿童孤独症是一种始发于婴幼儿期的广泛性发育障碍，我国对该疾病的研究起步较晚。尽管医学界已经针对孤独症进行了长达半世纪的研究，但是关于孤独症的成因仍然没有定论。随着研究深入，研究人员已经发现了部分可能影响孤独症的因素，包括遗传因素和感染与免疫因素等。而在临床上，孤独症主要表现为社会交往障碍、交流障碍以及狭隘兴趣和重复刻板行。DSM-V根据孤独症的临床表现给出了较为权威的诊断标准，但这个标准是描述性的。孤独症成因尚未确定，绝对化的标准也无法确定。

在应对孤独症方面，目前被广泛接受的思路是：干预为主，药物为辅。治疗方法包括但不限于结构化教育、行为治疗和人际关系发展干预。

在这项最新的研究中，研究团队通过观察接受 BF839 固体冻干粉末（10 g/袋，含 ≥106 CFU 的活菌，2 袋/天）及安慰剂的儿童，发现BF839 显著且安全地改善了 ASD 患儿的异常行为和胃肠道症状。

越来越多的动物研究[6-10]和临床试验[11-21]都报道了单一菌株或复合菌株益生菌可在一定程度上改善ASD行为表现及胃肠道症状，此研究结果提示BF839在改善ASD儿童行为症状方面显示出较为优秀的功效。有研究显示[18]，通过粪菌移植（FMT）2个月后，CARS评分较基线下降了10.8%（对照组仅下降了0.8%，P<0.001）；此研究干预16周后，在基线CARS≥30分的ASD儿童中，BF839降低了14.50%（对照组降低了5.93%，P=0.044），此研究结果与FMT疗效相似。

此研究发现，与安慰剂组及干预前对比，经BF839干预16w后，假小链双歧杆菌（Bifidobacterium pseudocatenulatum）、长双歧杆菌（Bifidobacterium longum）、两歧双歧杆菌（Bifidobacterium bifidum）丰度显著增加，我们的肠道菌群结果提示BF839可以促进ASD儿童肠道内双歧杆菌的生长，致使一些神经活性化合物的代谢功能显著变化，这可能是BF839能有效改善ASD儿童症状原因之一。

此研究结果对于人类使用肠道微生态制剂治疗神经发育障碍性疾病有重要的实践和理论意义。

* 论文链接：

Frontiers | Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial

* 参考文献：

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