{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T03:46:06Z","timestamp":1782618366558,"version":"3.54.5"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009035","name":"Program on Open Innovation Platform with Enterprises, Research Institute and Academia","doi-asserted-by":"publisher","award":["JPMJOP1833"],"award-info":[{"award-number":["JPMJOP1833"]}],"id":[{"id":"10.13039\/501100009035","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biomed"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Maternal separation (MS) is a widely used model of early-life stress, yet the biological pathways transmitting maternal stress signals to offspring remain incompletely understood. Breast milk represents a primary biological interface between mother and infant, and stress-induced changes in milk composition may influence offspring development through the gut microbiota\u2013brain axis. Here, we investigated whether MS alters the breast milk metabolome and whether such changes are associated with offspring gut microbiota composition, serum metabolite profiles, and serotonin-related gene expression in the prefrontal cortex. Using an integrated multi-omics approach in mice, we found that MS dams had elevated myristic acid and ethanolamine levels in breast milk. MS offspring exhibited reduced\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    abundance in the cecal microbiota, elevated myristic acid and decreased inosine in cecal contents, decreased inosine in serum, and reduced\n                    <jats:italic>Tph2<\/jats:italic>\n                    and\n                    <jats:italic>Htr1b<\/jats:italic>\n                    expression in the prefrontal cortex. Oral myristic acid supplementation in neonatal pups reduced\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    abundance, and inosine supplementation selectively increased\n                    <jats:italic>Htr1a<\/jats:italic>\n                    expression. Spearman correlation analyses using paired individual data revealed a negative association between cecal myristic acid and cecal inosine levels, and a positive correlation between cecal inosine and prefrontal\n                    <jats:italic>Tph2<\/jats:italic>\n                    expression, supporting quantitative links among these components. Collectively, these findings identify coordinated associations among maternal stress-induced milk fatty acid changes, offspring gut microbiota, microbial metabolites, and serotonin-related gene expression, providing an exploratory framework for understanding milk-mediated effects on the developing gut\u2013brain axis.\n                  <\/jats:p>","DOI":"10.1186\/s43556-026-00508-2","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T03:32:34Z","timestamp":1782617554000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal separation-induced changes in breast milk fatty acid composition are associated with altered gut microbiota and serotonergic gene expression in neonatal mice"],"prefix":"10.1186","volume":"7","author":[{"given":"Eman A.","family":"Mady","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein M.","family":"El-Husseiny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Kambe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Masukado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiho","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Terajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-1380","authenticated-orcid":false,"given":"Kentaro","family":"Nagaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"508_CR1","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.cobeha.2017.03.005","volume":"14","author":"NAV Derks","year":"2017","unstructured":"Derks NAV, Krugers HJ, Hoogenraad CC, Jo\u00ebls M, Sarabdjitsingh RA. Effects of early life stress on rodent hippocampal synaptic plasticity: a systematic review. Curr Opin Behav Sci. 2017;14:155\u201366. https:\/\/doi.org\/10.1016\/j.cobeha.2017.03.005.","journal-title":"Curr Opin Behav Sci"},{"key":"508_CR2","doi-asserted-by":"publisher","first-page":"7735","DOI":"10.1038\/ncomms8735","volume":"6","author":"G De Palma","year":"2015","unstructured":"De Palma G, Blennerhassett P, Lu J, Deng Y, Park AJ, Green W, et al. Microbiota and host determinants of behavioural phenotype in maternally separated mice. Nat Commun. 2015;6:7735. https:\/\/doi.org\/10.1038\/ncomms8735.","journal-title":"Nat Commun"},{"issue":"1","key":"508_CR3","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1080\/10253890.2017.1389883","volume":"21","author":"R Orso","year":"2018","unstructured":"Orso R, Wearick-Silva LE, Creutzberg KC, Centeno-Silva A, Glusman Roithmann L, Pazzin R, et al. Maternal behavior of the mouse dam toward pups: implications for maternal separation model of early life stress. Stress. 2018;21(1):19\u201327. https:\/\/doi.org\/10.1080\/10253890.2017.1389883.","journal-title":"Stress"},{"issue":"4","key":"508_CR4","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1002\/jdn.10329","volume":"84","author":"N Rowshan","year":"2024","unstructured":"Rowshan N, Anjomshoa M, Farahzad A, Bijad E, Amini-Khoei H. Gut\u2013brain barrier dysfunction bridge autistic-like behavior in mouse model of maternal separation stress: a behavioral, histopathological, and molecular study. Int J Dev Neurosci. 2024;84(4):314\u201327. https:\/\/doi.org\/10.1002\/jdn.10329.","journal-title":"Int J Dev Neurosci"},{"key":"508_CR5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.bbr.2013.03.040","volume":"248","author":"JP Aguggia","year":"2013","unstructured":"Aguggia JP, Su\u00e1rez MM, Rivarola MA. Early maternal separation: neurobehavioral consequences in mother rats. Behav Brain Res. 2013;248:25\u201331. https:\/\/doi.org\/10.1016\/j.bbr.2013.03.040.","journal-title":"Behav Brain Res"},{"key":"508_CR6","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.bbi.2022.10.005","volume":"107","author":"JD Galley","year":"2023","unstructured":"Galley JD, Mashburn-Warren L, Blalock LC, Lauber CL, Carroll JE, Ross KM, et al. Maternal anxiety, depression and stress affects offspring gut microbiome diversity and bifidobacterial abundances. Brain Behav Immun. 2023;107:253\u201364. https:\/\/doi.org\/10.1016\/j.bbi.2022.10.005.","journal-title":"Brain Behav Immun"},{"issue":"1","key":"508_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/01652176.2024.2349948","volume":"44","author":"EA Mady","year":"2024","unstructured":"Mady EA, Osuga H, Toyama H, El-Husseiny HM, Inoue R, Murase H, et al. Relationship between the components of mare breast milk and foal gut microbiome: shaping gut microbiome development after birth. Vet Q. 2024;44(1):1\u20139. https:\/\/doi.org\/10.1080\/01652176.2024.2349948.","journal-title":"Vet Q"},{"issue":"7","key":"508_CR8","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.3390\/nu16071074","volume":"16","author":"J Yu","year":"2024","unstructured":"Yu J, Zhang Y, Wells JCK, Wei Z, Bajaj-Elliott M, Nielsen DS, et al. A stress reduction intervention for lactating mothers alters maternal gut, breast milk, and infant gut microbiomes: data from a randomized controlled trial. Nutrients. 2024;16(7):1074. https:\/\/doi.org\/10.3390\/nu16071074.","journal-title":"Nutrients"},{"key":"508_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2023.105195","volume":"150","author":"EA Mady","year":"2023","unstructured":"Mady EA, Doghish AS, El-Dakroury WA, Elkhawaga SY, Ismail A, El-Mahdy HA, et al. 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