Association of breast milk miRNA with the pathogenesis of atopic dermatitis

• Project/Area Number: 18K16138
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: Chiba University
• Principal Investigator: Nakano Taiji 千葉大学, 医学部附属病院, 助教 (90708306)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 母乳 / microRNA / アトピー性皮膚炎 / 食物アレルギー / アレルギー

Outline of Final Research Achievements

In a high-risk birth cohort study, breastfeeding (OR: 2.64, 95% CI: 1.45-4.81) was found to be a risk factor for egg white sensitization at one year of age. These results suggest that immune substances and microRNAs in breast milk may be involved in egg white sensitization.
Therefore, we analyzed miRNA expression in breast milk samples from five atopic dermatitis (AD) subjects and five non-AD subjects, and found that hsa-miR-342-5p was significantly lower in the AD group than in the non-AD group. In silico analysis showed that hsa-miR-342-5p was involved in VEGF, TGFb signaling and may be involved in the development of allergic diseases.

Academic Significance and Societal Importance of the Research Achievements

アトピー性皮膚炎含むアレルギー疾患は有病率も高く、QOLを著しく低下させるためその予防や病態解明は社会的意義が高い。また、離乳食が始まる前の新生児期から乳児期は母乳もしくは人工乳が唯一の栄養であり児に与える影響は大きい。母乳栄養が卵白感作のリスク因子となることが我々の独立した２つの出生コホート研究から分かっており、アレルギー疾患発症にも母乳成分が関与している可能性が示唆された。今回は母乳中のmiRNAに着目して研究を行い、母乳中のある特定のmiRNAがアトピー性皮膚炎発症した児において低値であることが判明したことで今後さらに母乳中成分の関わりが着目される。

Research Products

• [Journal Article] Increase in eosinophil-derived neurotoxin level in school children with allergic disease (2022)
  • Author(s): Kim Chang-Keun、Kang Dong Yoon、Callaway Zak、Kim Kyoung Soo、Kwon Eun Mi、Yamaide Fumiya、Nakano Taiji、Suzuki Yoichi、Mashimo Yoichi、Hata Akira、Okamoto Yoshitaka、Shimojo Naoki
  • Journal Title: Asia Pacific Allergy Volume: 12 Issue: 3 Pages: e25-e25
  • DOI: 10.5415/apallergy.2022.12.e25
  • Peer Reviewed
• [Journal Article] Association of the Maternal Gut Microbiota/Metabolome with Cord Blood CCL17 (2021)
  • Author(s): Tanabe Hiromi、Sakurai Kenichi、Nakanishi Yumiko、Kato Tamotsu、Kawasaki Yohei、Nakano Taiji、Yamaide Fumiya、Taguchi-Atarashi Naoko、Shiko Yuki、Takashima Ikumi、Watanabe Masahiro、Ochiai Shingo、Ohno Hiroshi、Fukuoka Hideoki、Shimojo Naoki、Mori Chisato
  • Journal Title: Nutrients Volume: 13 Issue: 8 Pages: 2837-2837
  • DOI: 10.3390/nu13082837
  • Peer Reviewed
• [Journal Article] Long-chain saturated fatty acids in breast milk are associated with the pathogenesis of atopic dermatitis via induction of inflammatory ILC3s. (2021)
  • Author(s): 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.
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 13109-13109
  • DOI: 10.1038/s41598-021-92282-0
  • Peer Reviewed / Open Access
• [Journal Article] Precision medicine reaching out to the patients in allergology - a German-Japanese workshop report (2021)
  • Author(s): Pfaar O, Blumchen K, Boateng E, Hamelmann E, Iinuma T, Jakob T, Krauss-Etschmann S, Nagase H, Nakajima S, Nakano T, Renz H, Sato S, Taube C, Wagenmann M, Werfel T, Worm M, Izuhara K
  • Journal Title: Allergologie select Volume: 5 Issue: 01 Pages: 162-179
  • DOI: 10.5414/alx02234e
  • Peer Reviewed / Open Access
• [Journal Article] Breastfeeding Promotes Egg White Sensitization in Early Infancy (2020)
  • Author(s): Nakano T, Ochiai S, Suzuki S, Yamaide F, Morita Y, Inoue Y, Arima T, Kojima H, Suzuki H, Nagai K, Morishita N, Hata A, Shozu M, Suzuki Y, Taniguchi M, Takemori T, Kohno Y, Shimojo N.
  • Journal Title: Pediatr Allergy Immunol Volume: 31(3) Issue: 3 Pages: 315-318
  • DOI: 10.1111/pai.13208
  • Peer Reviewed
• [Journal Article] Staphylococcus Agr virulence is critical for epidermal colonization and associates with atopic dermatitis development (2020)
  • Author(s): Nakamura Y, Takahashi H, Takaya A, Inoue Y, Katayama Y, Kusuya Y, Shoji T, Takada S, Nakagawa S, Oguma R, Saito N, Ozawa N, Nakano T, Yamaide F, Dissanayake E, Suzuki S, Villaruz A, Varadarajan S, Matsumoto M, Kobayashi T, Kono M, Sato Y, Akiyama M, Otto M, Matsue H, Nunez G, Shimojo N.
  • Journal Title: Sci Transl Med. Volume: 8 Issue: 551 Pages: 4068-4068
  • DOI: 10.1126/scitranslmed.aay4068
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Skin Care and Synbiotics for Prevention of Atopic Dermatitis or Food Allergy in Newborn Infants: A 2 × 2 Factorial, Randomized, Non-Treatment Controlled Trial (2019)
  • Author(s): Dissanayake E, Tani Y, Nagai K, Sahara M, Mitsuishi C, Togawa Y, Suzuki Y, Nakano T, Yamaide F, Ohno H, Shimojo N.
  • Journal Title: Int Arch Allergy Immunol Volume: 180(3) Issue: 3 Pages: 202-211
  • DOI: 10.1159/000501636
  • Peer Reviewed
• [Journal Article] Association of the Maternal Microbiome in Japanese Pregnant Women With the Cumulative Prevalence of Dermatitis in Early Infancy: A Pilot Study From the Chiba Study of Mother and Child Health Birth Cohort (2019)
  • Author(s): Tanabe H, Sakurai K, Kato T, Kawasaki Y, Nakano T, Yamaide F, Taguchi-Atarashi N, Watanabe M, Ochiai S, Ohno H, Fukuoka H, Shimojo N, Mori C.
  • Journal Title: World Allergy Organ J Volume: 1;12(10) Issue: 10 Pages: 100065-100065
  • DOI: 10.1016/j.waojou.2019.100065
  • Peer Reviewed / Open Access
• [Journal Article] Soluble CD14 in Breast Milk and Its Relation to Atopic Manifestations in Early Infancy (2019)
  • Author(s): Fikri B, Tani Y, Nagai K, Sahara M, Mitsuishi C, Togawa Y, Nakano T, Yamaide F, Ohno H, Shimojo N.
  • Journal Title: Nutrients Volume: 5;11(9) Issue: 9 Pages: 2118-2118
  • DOI: 10.3390/nu11092118
  • Peer Reviewed / Open Access
• [Journal Article] Hsa-mir-144-3p expression is increased in umbilical cord serum of infants with atopic dermatitis. (2019)
  • Author(s): Dissanayake E, Inoue Y, Ochiai S, Eguchi A, Nakano T, Yamaide F, Hasegawa S, Kojima H, Suzuki H, Mori C, Kohno Y, Taniguchi M, Shimojo N
  • Journal Title: J Allergy Clin Immunol. Volume: Jan;143(1) Issue: 1 Pages: 447-450
  • DOI: 10.1016/j.jaci.2018.09.024
  • Peer Reviewed
• [Presentation] ビタミンDによるアレルギー発症予防の可能性 (2021)
  • Author(s): 中野 泰至
  • Organizer: 日本小児アレルギー学会
• [Presentation] Breastfeeding is a risk factor of egg white sensitization (2020)
  • Author(s): Taiji Nakano
  • Organizer: JSA/WAO Joint Congress 2020
  • Int'l Joint Research
• [Presentation] Identification of microRNAs in human breast milk related to atopic dermatitis (2019)
  • Author(s): Taiji Nakano
  • Organizer: inVIVO
  • Int'l Joint Research
• [Presentation] MicroRNA in pediatric allergic diseases (2019)
  • Author(s): Taiji Nakano
  • Organizer: Annual Congress of Korean Academy of Pediatric Allergy and Respiratory Disease
  • Int'l Joint Research / Invited
• [Presentation] Risk factors of pediatric allergic diseases. Insights from birth cohort study in Chiba, Japan (2019)
  • Author(s): Taiji Nakano
  • Organizer: DGAKI-JSA Joint Meeting
  • Int'l Joint Research / Invited
• [Presentation] 千葉市でのハイリスク出生コホート研究（CHIBA study）における7歳までの感作率及びアレルギー疾患の推移 (2019)
  • Author(s): 中野泰至、山出史也、下条直樹
  • Organizer: 日本小児アレルギー学会
• [Presentation] Identification of microRNAs in human breast milk related to atopic dermatitis (2018)
  • Author(s): Taiji Nakano
  • Organizer: European Academy of Allergy and Clinical Immunology
  • Int'l Joint Research
• [Funded Workshop] in VIVO meeting (2019)