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<p>An unhealthy diet disrupts feeding behavior and the gut microbiota, but whether early-life dietary effects persist, or can be restored later in life, remains unclear. We investigated whether microbiota-targeted interventions (FOS + GOS or <i>Bifidobacterium longum</i> 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<sup>+</sup> 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 + GOS induced extensive microbiome compositional shifts and sex-specific restoration of gut-brain pathways, while <i>B. longum</i> 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.</p>

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Bifidobacterium longum and prebiotic interventions restore early-life high-fat/high-sugar diet-induced alterations in feeding behavior in adult mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月24日

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  • Cristina Cuesta-Marti,
  • Eduardo Ponce-España,
  • Friederike Uhlig,
  • Iris Stoltenborg,
  • Luiza A. Wasiewska,
  • Lamiah Kareem,
  • Dara Hedayatpour,
  • Loreto Olavarría-Ramírez,
  • Cristina Rosell-Cardona,
  • Thomaz. F. S. Bastiaanssen,
  • Gabriel. S. S. Tofani,
  • Benjamin Valderrama,
  • Klara Vlckova,
  • Suzanne L. Dickson,
  • Aonghus Lavelle,
  • Catherine Stanton,
  • R. Paul Ross,
  • John F. Cryan,
  • Timothy G. Dinan,
  • Gerard Clarke,
  • Siobhain M. O’Mahony,
  • Harriët Schellekens

摘要

An unhealthy diet disrupts feeding behavior and the gut microbiota, but whether early-life dietary effects persist, or can be restored later in life, remains unclear. We investigated whether microbiota-targeted interventions (FOS + GOS or Bifidobacterium longum 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+ 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 + GOS induced extensive microbiome compositional shifts and sex-specific restoration of gut-brain pathways, while B. longum 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.