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Early postnatal antibiotic-associated gut microbiota alterations might promote long-term lipid metabolism via brown

Huijing Liang1,2, Fengling Jiang1,3, Lei Ren1

  • 1Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.

Gut Microbes
|May 5, 2026
PubMed

Insights

Early life gut microbiota disruption, via antibiotics in mice, surprisingly improved adult lipid metabolism. This effect, linked to enhanced brown adipose tissue (BAT) function, suggests early microbiota targeting for obesity prevention.

Area of Science:

  • Metabolic programming
  • Gut microbiota
  • Adipose tissue biology

Background:

  • The Developmental Origins of Health and Disease (DOHaD) theory highlights early life as critical for long-term metabolic health.
  • The gut microbiota is increasingly recognized as a key mediator in early-life metabolic programming.
  • Perturbations during this window may have lasting effects on health outcomes.

Purpose of the Study:

  • To investigate the long-term effects of early postnatal gut microbiota disruption on adult lipid metabolism.
  • To examine the underlying mechanisms involving thermogenic adipose tissue programming and gut microbiota remodeling.
  • To assess sex-specific differences in response to early-life perturbations.

Main Methods:

  • Neonatal mice received antibiotic treatment to perturb the gut microbiota.
  • Adult mice were challenged with a high-fat diet to assess lipid metabolism.
  • Mechanisms were investigated through analysis of adipose tissue (brown and white) and gut microbiota structure.
  • Interleukin-6 signaling and M2 macrophage polarization were examined.

Main Results:

  • Early antibiotic exposure significantly disrupted gut microbiota development.
  • Surprisingly, this disruption attenuated high-fat diet-induced lipid disturbances in adulthood, particularly in males.
  • Metabolic improvements were associated with enhanced brown adipose tissue (BAT) thermogenic activation, not white adipose tissue browning.
  • Gut microbiota alterations were linked to enhanced BAT development via IL-6 signaling and M2 macrophage polarization.

Conclusions:

  • Early-life gut microbiota perturbations can have long-term, sex-specific effects on lipid metabolism.
  • Enhanced BAT development and thermogenesis, potentially mediated by IL-6 and M2 macrophages, contribute to improved metabolic health.
  • The gut microbiota represents a modifiable target for early-life interventions aimed at preventing obesity and metabolic disease.

Keywords:
Early postnatalantibioticbrown adipose tissuegut microbiotalipid metabolismmetabolic programming

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