Implications of oral streptococcal bacteriophages in autism spectrum disorder.

Implications of oral streptococcal bacteriophages in autism spectrum disorder.
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DOI:
10.1038/s41522-022-00355-3
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发表时间:
2022-11-18
影响因子:
9.2
通讯作者:
Kang, Yu
Kang, Yu
中科院分区:
生物学1区
文献类型:
--
作者:
Tong, Zhan;Zhou, Xin;Chu, Yanan;Zhang, Tianxu;Zhang, Jie;Zhao, Xiaoyan;Wang, Zuqun;Ding, Rui;Meng, Qingren;Yu, Jun;Wang, Juan;Kang, Yu

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越来越多的证据表明自闭症谱系障碍 (ASD) 的口腔和肠道微生物群发生了改变,但人们对噬菌体的改变和作用知之甚少,尤其是在 ASD 受试者的口腔微生物群中。我们纳入了自闭症谱系障碍 (n = 26) 和神经典型受试者 (n = 26),控制了口腔卫生,并对口腔和粪便样本 (n = 104) 的宏基因组进行了鸟枪法测序和比较。我们观察到与肠道相当的广泛且多样化的口腔噬菌体,以及个体内口腔到肠道噬菌体菌株转移的清晰信号。然而,这两个位点的总体噬菌体组差异很大,并且自闭症谱系障碍和对照受试者之间的口腔群落相似性更低。 ASD 口腔噬菌体的丰度和 α 多样性显着降低,但链球菌噬菌体异常富集,通常在群落中占主导地位。链球菌噬菌体的过度表达伴随着口腔链球菌毒力因子和链球菌细菌的丰富,所有这些都与 ASD 临床表现的严重程度呈正相关。在肠道菌群的平行采样中没有观察到这些变化,这表明链球菌噬菌体过度富集与 ASD 发病机制之间存在先前未知的口腔特异性关联。这些发现为独立的微生物群-口-脑联系提供了新的证据,加深了我们对噬菌体和口腔微生物群的生长动态如何促进自闭症谱系障碍的理解,并指出了新的有效治疗方法。
Growing evidence suggests altered oral and gut microbiota in autism spectrum disorder (ASD), but little is known about the alterations and roles of phages, especially within the oral microbiota in ASD subjects. We enrolled ASD (n = 26) and neurotypical subjects (n = 26) with their oral hygiene controlled, and the metagenomes of both oral and fecal samples (n = 104) are shotgun-sequenced and compared. We observe extensive and diverse oral phageome comparable to that of the gut, and clear signals of mouth-to-gut phage strain transfer within individuals. However, the overall phageomes of the two sites are widely different and show even less similarity in the oral communities between ASD and control subjects. The ASD oral phageome exhibits significantly reduced abundance and alpha diversity, but the Streptococcal phages there are atypically enriched, often dominating the community. The over-representation of Streptococcal phages is accompanied by enriched oral Streptococcal virulence factors and Streptococcus bacteria, all exhibiting a positive correlation with the severity of ASD clinical manifestations. These changes are not observed in the parallel sampling of the gut flora, suggesting a previously unknown oral-specific association between the excessive Streptococcal phage enrichment and ASD pathogenesis. The findings provide new evidence for the independent microbiome-mouth-brain connection, deepen our understanding of how the growth dynamics of bacteriophages and oral microbiota contribute to ASD, and point to novel effective therapeutics.
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