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We investigated whether microbiota-targeted interventions (FOS\u2009+\u2009GOS or\n                    <jats:italic>Bifidobacterium longum<\/jats:italic>\n                    APC1472) could restore early-life high-fat\/high-sugar (HFHS) diet-induced feeding alterations in adult female and male mice. HFHS exposure exclusively in early-life induced persistent, sex-specific feeding alterations in adult mice, despite normalized body weight. Early-life HFHS diet reduced hypothalamic cells expressing feeding-related markers (POMC, GHSR, PNOC, NOD2) in adult mice. Females were more vulnerable, with reduced LEPR\n                    <jats:sup>+<\/jats:sup>\n                    cells and disrupted arginine\/tryptophan metabolism, while males showed impaired peptidoglycan sensing and steroid metabolism. We show that microbiota interventions restore these effects via distinct mechanisms. FOS\u2009+\u2009GOS induced extensive microbiome compositional shifts and sex-specific restoration of gut-brain pathways, while\n                    <jats:italic>B. longum<\/jats:italic>\n                    APC1472 induced greater behavioral restoration with minimal microbiome compositional changes. These findings highlight sex-specific vulnerabilities and mechanism-dependent therapeutic potential of microbiota-based interventions after exposure to early-life unhealthy diets.\n                  <\/jats:p>","DOI":"10.1038\/s41467-026-68968-2","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:03:40Z","timestamp":1771927420000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bifidobacterium longum and prebiotic interventions restore early-life high-fat\/high-sugar diet-induced alterations in feeding behavior in adult mice"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-9394","authenticated-orcid":false,"given":"Cristina","family":"Cuesta-Marti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6197-0041","authenticated-orcid":false,"given":"Eduardo","family":"Ponce-Espa\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-1951","authenticated-orcid":false,"given":"Friederike","family":"Uhlig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Stoltenborg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiza A.","family":"Wasiewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamiah","family":"Kareem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dara","family":"Hedayatpour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Olavarr\u00eda-Ram\u00edrez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3627-9413","authenticated-orcid":false,"given":"Cristina","family":"Rosell-Cardona","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6891-734X","authenticated-orcid":false,"given":"Thomaz. 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Zenodo https:\/\/doi.org\/10.5281\/ZENODO.17831151 (2025).","DOI":"10.5281\/ZENODO.17831151"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68968-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68968-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68968-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:04:01Z","timestamp":1771927441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-68968-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":174,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["68968"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-68968-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"2 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing non-financial interests. The following competing financial interests are declared: G.C. received honoraria from Janssen, Probi, Ingelheim Boehringer and Apsen, as an invited speaker, and research funding from Pharmavite, Reckitt, Tate & Lyle PLC, Nestle, Fonterra and is or has been a paid consultant for Heel Pharmaceuticals, Bayer Healthcare, Yakult and Zentiva; H.S. has obtained research funding from Pharmavite, Cremo, Tate & Lyle PLC, Pepsico, and Fonterra. This support did not influence or constrain the study design, data analysis, collection, data interpretation, writing or overall content of this manuscript. H.S., T.D., J.F.C., and C.S. are inventors on a patent for other findings previously identified with the in-house bacterial strain used in the present work (filed and pending, EP17187989.3, entitled: \u201c\n                      Bifidobacterium longum\n                      APC1472 for treating obesity and weight management\u201d). The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1653"}}