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Updated: May 6, 2026

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Microbiota Co-Metabolism Alterations Precede Changes in the Host Metabolism in the Early Stages of Diet-Induced MASLD

María Martín-Grau1,2, Pilar Casanova1,2, Laura Moreno-Morcillo1,2

  • 1Departament de Patologia, Universitat de València, 46010 Valencia, Spain.

International Journal of Molecular Sciences
|February 13, 2025
PubMed

Insights

Early metabolic-dysfunction-associated steatotic liver disease (MASLD) development involves gut microbiota changes preceding host metabolic alterations. This study tracked MASLD progression in rats, revealing microbiota shifts before subclinical liver steatosis.

Area of Science:

  • Gastroenterology
  • Metabolomics
  • Microbiome Research

Background:

  • Metabolic-dysfunction-associated steatotic liver disease (MASLD) impacts 30% of the global population.
  • Sexual dimorphism and gut microbiota are crucial in early MASLD development.

Purpose of the Study:

  • Investigate metabolic changes during early, subclinical MASLD progression.
  • Identify the sequence of events in MASLD initiation.
  • Evaluate the impact of sexual dimorphism and gut microbiota on early MASLD stages.

Main Methods:

  • Longitudinal study of male and female Wistar rats on chow or high-fat diet (HFD) for 21 weeks.
  • Regular metabolomic analysis of serum, urine, and faeces.
  • 16S rRNA gene sequencing for gut microbiota analysis over time.

Main Results:

  • A 3-week HFD reduced gut bacterial diversity and altered faecal/urine metabolomes.
  • HFD induced changes in host-microbiota co-metabolites across liver, blood, urine, and faeces.
  • Gut microbiota diversity and co-metabolism alterations preceded host metabolic changes.

Conclusions:

  • Gut microbiota alterations play a significant role in the early, subclinical stages of MASLD.
  • Host-microbiota co-metabolism is critical in MASLD initiation.
  • Changes in gut microbiota diversity precede host metabolic shifts in early liver steatosis.
Keywords:
MASLDNMRfaecal microbiotametabolomicssexual dimorphism

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