With great interest, we read the article by Lou et al ,1 who reported deviated gut microbiota in children with autism spectrum disorders (ASD). Recently, increasing studies have revealed abnormalities in extraneural tissues, particularly the gastrointestinal (GI) tract.2 Besides, the important role of lipids in the gut-brain axis of ASD is highlighted by their involvement in neurodevelopmental processes disrupted in ASD3 and their susceptibility to remodelling through intestinal intervention.4 In this study, we explored disrupted lipid profiles using lipidomics combined with single-cell transcriptomics, faecal metagenomics and cytokine profiling in multiple tissues of Chd8 -mutant ASD mice (HET), examining how skewed lipidomes were related to ASD-relevant phenotypes. We analysed the lipidome of five tissues—brain, gut, liver, serum and GI contents in HET and wild type (WT) mice, and performed inflammatory cytokine assays and three behavioural tests in the same mice (figure 1a). We identified 726 lipid species in five tissues (online supplemental figure 1a), categorising them into five groups. Analysis of the relative abundance of these lipid species revealed significantly shifted lipidomes and differentially abundant lipid species in all five tissues of HET compared with WT (figure 1b,c). We further calculated the numbers of lipid species with increased or decreased abundance in total (figure 1d) and each lipid category (figure 1e), and observed that glycerophospholipids showed the highest number of changes among lipid categories. Besides, we observed altered levels of gut bacteria-specific lipid species in the GI contents, with increased levels of hydroxy and oxo fatty acids produced by Lactobacillus 5 and glycerophospholipids incorporating these fatty acids in the GI contents of HET. In contrast, PE-ceramides, produced by several bacteria, including Bacteroides ,6 exhibited reduced levels (figure 1f and online supplemental table 1).### Supplementary data [gutjnl-2024-332972supp001.pdf] Figure 1 Disrupted lipid profiles in multiple tissues of Chd8 -mutant …

中文翻译：

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通过整合脂质组学和单细胞转录组学，揭示 Chd8 突变型 ASD 小鼠多个组织中的脂质组学破坏


我们怀着极大的兴趣阅读了 Lou 等人 1 的文章，他们报道了自闭症谱系障碍 （ASD） 儿童的肠道微生物群偏差。最近，越来越多的研究揭示了神经外组织异常，尤其是胃肠道 （GI） .2 此外，脂质在 ASD 肠脑轴中的重要作用还体现在它们参与 ASD3 中断的神经发育过程以及它们对通过肠道干预重塑的敏感性.4 在这项研究中，我们使用脂质组学结合单细胞转录组学探索了被破坏的脂质谱， Chd8 突变型 ASD 小鼠 （HET） 多个组织中的粪便宏基因组学和细胞因子分析，检查偏斜脂质组与 ASD 相关表型的关系。我们分析了 HET 和野生型 （WT） 小鼠的脑、肠道、肝脏、血清和 GI 含量这五个组织的脂质组，并在同一只小鼠中进行了炎性细胞因子测定和三种行为测试（图 1a）。我们在 5 个组织中鉴定了 726 种脂质（在线补充图 1a），将它们分为五组。对这些脂质种类的相对丰度的分析显示，与 WT 相比，HET 的所有五个组织中的脂质组显着偏移和脂质种类差异丰度（图 1b，c）。我们进一步计算了总丰度增加或减少的脂质种类的数量（图 1d）和每种脂质类别（图 1e），并观察到甘油磷脂在脂质类别中显示出最高的变化数量。 此外，我们观察到胃肠道细菌特异性脂质种类水平在 GI 含量中发生变化，乳酸菌 5 产生的羟基和氧代脂肪酸水平增加，甘油磷脂将这些脂肪酸掺入 HET 的 GI 含量中。相比之下，由几种细菌（包括拟杆菌门）6 产生的 PE 神经酰胺水平降低（图 1f 和在线补充表 1）.### 补充数据 [gutjnl-2024-332972supp001.pdf] 图 1 Chd8 突变体多个组织中的脂质谱被破坏......