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

## TL;DR

Early-life high-fat/high-sugar diets cause lasting feeding issues in adult mice, which can be reversed with specific gut microbiota interventions.

## Contribution

The study reveals sex-specific effects of early-life diets and shows that microbiota interventions can restore feeding behavior through distinct mechanisms.

## Key findings

- Early-life HFHS diets cause persistent, sex-specific feeding alterations in adult mice.
- Bifidobacterium longum and prebiotics restore these effects via different mechanisms.
- Females show greater vulnerability with disrupted metabolism and fewer hypothalamic cells.

## Abstract

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.

Here, the authors show that early-life high-fat/high-sugar diet induces sex-specific alterations in adult feeding behavior, hypothalamic transcriptome and blood metabolome, with Bifidobacterium longum and prebiotic FOS + GOS administration restoring these effects via distinct mechanisms, highlighting their therapeutic potential.