Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s

Abstract 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...

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Autores principales:	Weng Sheng Kong, Naohiro Tsuyama, Hiroko Inoue, Yun Guo, Sho Mokuda, Asako Nobukiyo, Nobuhiro Nakatani, Fumiya Yamaide, Taiji Nakano, Yoichi Kohno, Kazutaka Ikeda, Yumiko Nakanishi, Hiroshi Ohno, Makoto Arita, Naoki Shimojo, Masamoto Kanno
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/95ab8af9fd2e4b68b71d4d1fb2c3d1f5
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spelling	oai:doaj.org-article:95ab8af9fd2e4b68b71d4d1fb2c3d1f52021-12-02T18:02:54ZLong-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s10.1038/s41598-021-92282-02045-2322https://doaj.org/article/95ab8af9fd2e4b68b71d4d1fb2c3d1f52021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92282-0https://doaj.org/toc/2045-2322Abstract 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.Weng Sheng KongNaohiro TsuyamaHiroko InoueYun GuoSho MokudaAsako NobukiyoNobuhiro NakataniFumiya YamaideTaiji NakanoYoichi KohnoKazutaka IkedaYumiko NakanishiHiroshi OhnoMakoto AritaNaoki ShimojoMasamoto KannoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Weng Sheng Kong Naohiro Tsuyama Hiroko Inoue Yun Guo Sho Mokuda Asako Nobukiyo Nobuhiro Nakatani Fumiya Yamaide Taiji Nakano Yoichi Kohno Kazutaka Ikeda Yumiko Nakanishi Hiroshi Ohno Makoto Arita Naoki Shimojo Masamoto Kanno Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
description	Abstract 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.
format	article
author	Weng Sheng Kong Naohiro Tsuyama Hiroko Inoue Yun Guo Sho Mokuda Asako Nobukiyo Nobuhiro Nakatani Fumiya Yamaide Taiji Nakano Yoichi Kohno Kazutaka Ikeda Yumiko Nakanishi Hiroshi Ohno Makoto Arita Naoki Shimojo Masamoto Kanno
author_facet	Weng Sheng Kong Naohiro Tsuyama Hiroko Inoue Yun Guo Sho Mokuda Asako Nobukiyo Nobuhiro Nakatani Fumiya Yamaide Taiji Nakano Yoichi Kohno Kazutaka Ikeda Yumiko Nakanishi Hiroshi Ohno Makoto Arita Naoki Shimojo Masamoto Kanno
author_sort	Weng Sheng Kong
title	Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
title_short	Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
title_full	Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
title_fullStr	Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
title_full_unstemmed	Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s
title_sort	long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ilc3s
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/95ab8af9fd2e4b68b71d4d1fb2c3d1f5
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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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