Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s.
Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s.
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母乳中的长链饱和脂肪酸通过诱导炎性ILC3与特应性皮炎的发病机制相关。
DOI：
10.1038/s41598-021-92282-0
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发表时间：
2021-06-23
影响因子：
4.6
通讯作者：
Kanno M
中科院分区：
文献类型：
--
作者：
Kong WS;Tsuyama N;Inoue H;Guo Y;Mokuda S;Nobukiyo A;Nakatani N;Yamaide F;Nakano T;Kohno Y;Ikeda K;Nakanishi Y;Ohno H;Arita M;Shimojo N;Kanno M
母乳喂养会影响婴儿免疫系统的发育，甚至可能影响生命后期的各种免疫反应。母乳为婴儿的生长发育提供了丰富的早期营养来源。然而，母乳中某些化合物的存在，与不健康的生活方式或哺乳母亲的饮食有关，可能对婴儿产生负面影响。基于对特应性皮炎（AD）的队列研究，我们发现母乳中存在损伤相关分子模式（DAMPs）活性。通过非靶向代谢组学分析，我们确定了长链饱和脂肪酸（LCSFA）作为DAMPs（+）的生物标志物。类似地，在一个小鼠模型中，母乳喂养的后代被喂食含有高LCSFA的牛奶，结果显示阿尔茨海默病的发病年龄较晚。我们证明LCSFA是一种损伤相关的分子模式，它在肠道中启动一系列涉及3型先天淋巴样细胞（ILC3s）的炎症事件。在肠道中观察到炎性ILC3s的显著增加，这些ILC3s向皮肤的迁移可能是AD的潜在触发因素。从肠道分离ILC3s的基因表达分析显示，ILC3s和趋化因子/趋化因子受体增加的基因上调，这可能在ILC向皮肤迁移中发挥作用。即使在没有适应性免疫的情况下，喂食高lccsfa牛奶的Rag1基因敲除小鼠也会出现湿疹，并伴有肠道ILC3s的增加。我们还发现，ad易发的PA乳喂养小鼠的肠道微生物群与非ad的OA/ND乳喂养小鼠不同。本研究提示，婴儿早期暴露于LCSFAs可能会影响肠道先天免疫平衡，导致ILC3s增殖、白细胞介素-17和白细胞介素-22产生的高度炎症环境，这些因素可能是AD的潜在触发或加重因素。
Breastfeeding influences the immune system development in infants and may even affect various immunological responses later in life. Breast milk provides a rich source of early nutrition for infant growth and development. However, the presence of certain compounds in breast milk, related to an unhealthy lifestyle or the diet of lactating mothers, may negatively impact infants. Based on a cohort study of atopic dermatitis (AD), we find the presence of damage-associated molecular patterns (DAMPs) activity in the mother’s milk. By non-targeted metabolomic analysis, we identify the long-chain saturated fatty acids (LCSFA) as a biomarker DAMPs (+) breast milk samples. Similarly, a mouse model in which breastfed offspring are fed milk high in LCSFA show AD onset later in life. We prove that LCSFA are a type of damage-associated molecular patterns, which initiate a series of inflammatory events in the gut involving type 3 innate lymphoid cells (ILC3s). A remarkable increase in inflammatory ILC3s is observed in the gut, and the migration of these ILC3s to the skin may be potential triggers of AD. Gene expression analysis of ILC3s isolated from the gut reveal upregulation of genes that increase ILC3s and chemokines/chemokine receptors, which may play a role in ILC migration to the skin. Even in the absence of adaptive immunity, Rag1 knockout mice fed a high-LCSFA milk diet develop eczema, accompanied by increased gut ILC3s. We also present that gut microbiota of AD-prone PA milk-fed mice is different from non-AD OA/ND milk-fed mice. Here, we propose that early exposure to LCSFAs in infants may affect the balance of intestinal innate immunity, inducing a highly inflammatory environment with the proliferation of ILC3s and production of interleukin-17 and interleukin-22, these factors may be potential triggers or worsening factors of AD.
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影响因子：
8
作者：
通讯作者：
--
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
6.5
作者：
Cochez, Perrine M.;Michiels, Camille;Dumoutier, Laure
通讯作者：
Dumoutier, Laure
影响因子：
10.5
作者：
Du, Yang;Yang, Marie;Wan, Yihong
通讯作者：
Wan, Yihong
影响因子：
3.1
作者：
Brooke, HC
通讯作者：
Brooke, HC