Berberine alters gut microbial function through modulation of bile acids.

Area of Science:

• Microbiology
• Metabolomics
• Systems Biology

Background:

• Berberine (BBR) is a plant-derived nutraceutical with historical use for diarrhea and modern application in improving lipid profiles.
• BBR's lipid-lowering effects are linked to increased bile acid synthesis and excretion.
• The impact of BBR on gut microbiome composition and function remains incompletely understood, particularly the interplay with bile acids.

Purpose of the Study:

• To investigate the effects of Berberine (BBR) on gut microbiome function and bile acid metabolism.
• To establish a model for identifying correlations between bile acids and bacterial transcripts under BBR treatment.
• To elucidate the mechanisms by which BBR influences the gut microbial community.

Main Methods:

• Germfree mice were colonized with a defined bacterial consortium (B4PC2) capable of bile acid metabolism.
• Multi-omics analyses including bile acid metabolomics, 16S rDNA sequencing, and cecal metatranscriptomics were employed.
• Network analysis was used to correlate bile acid profiles with bacterial gene expression in the presence and absence of BBR.

Main Results:

• BBR treatment led to significant alterations in gut microbial network topology and functional connectivity, despite no changes in alpha or beta diversity.
• Cecal bile acid concentrations, particularly deoxycholic acid (DCA), were significantly increased by BBR.
• Transcriptome analysis revealed species-specific and common functional responses to BBR, including upregulation of Na+/H+ antiporter, cell wall processes, and metabolic pathways.

Conclusions:

• BBR significantly impacts gut microbiome function and bile acid metabolism in vivo.
• The study highlights the intricate network between bile acids and bacterial gene expression influenced by BBR.
• Findings provide a foundation for developing targeted pharmaceutical interventions based on BBR's microbiome-modulating effects.