Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome.
Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome.
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DOI：
10.1194/jlr.ra120000950
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发表时间：
2021
影响因子：
6.5
通讯作者：
Johnson EL
中科院分区：
文献类型：
--
作者：
Lee MT;Le HH;Johnson EL
肠道微生物组的功能对宿主代谢健康有越来越多的影响，饮食是对微生物组组成最重要的影响之一。饮食与肠道微生物组之间的密切联系表明，包括脂质在内的各种常量营养素发挥着关键作用，但个别类别的饮食脂质如何与微生物组相互作用仍在很大程度上未知。鞘脂是大多数食物的生物活性成分，也由主要的肠道微生物产生。这使得鞘脂成为塑造饮食-微生物组相互作用的有趣候选物。在这里，我们使用了一种基于点击化学的方法来跟踪生物正交膳食ω-炔基二氢鞘氨醇[二氢鞘氨醇炔（SAA）]掺入到小鼠肠道微生物群落（生物正交标记）。我们通过对含SAA的微生物进行基于荧光的分选（Sort）、16 S rRNA基因测序以鉴定鞘脂相互作用微生物（Seq）和比较代谢组学以鉴定微生物组（Spec）同化SAA的产物来鉴定微生物和SAA特异性代谢产物。总之，这种被称为生物正交标记-排序-序列-规格（BOSSS）的方法揭示了SAA同化几乎完全由肠道拟杆菌执行，表明鞘脂产生细菌在加工膳食鞘氨醇中起主要作用。SAA处理小鼠盲肠微生物群的比较代谢组学显示SAA转化为一系列二氢神经酰胺，与拟杆菌和双歧杆菌的代谢活性一致。此外，还鉴定了其他鞘脂相互作用微生物，重点关注拟杆菌和双歧杆菌代谢膳食鞘脂的未表征能力。我们的结论是，BOSSS提供了一个平台来研究几乎任何炔标记的代谢物在饮食-微生物组相互作用中的通量。
Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions. Here, we used a click chemistry-based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine [sphinganine alkyne (SAA)] into the murine gut microbial community (bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet-microbiome interactions.