The Probiotic Parabacteroides johnsonii Ameliorates Metabolic Disorders Through Promoting BCAAs to BSCFAs Conversion

Area of Science:

• Microbiology
• Metabolic Disorders
• Gut Microbiome

Background:

• Parabacteroides spp. show therapeutic potential for metabolic disorders.
• The specific role of Parabacteroides johnsonii in metabolic disorders remains uncharacterized.

Purpose of the Study:

• To investigate the role of Parabacteroides johnsonii in metabolic disorders.
• To elucidate the mechanisms by which P. johnsonii exerts its effects.

Main Methods:

• Correlation analysis of P. johnsonii abundance with metabolic parameters in obese patients.
• Oral administration of P. johnsonii in high-fat diet-induced obese mice.
• Analysis of gut barrier integrity, systemic inflammation, and metabolite profiles.
• Investigating the effect of isobutyrate and stachyose interventions.

Main Results:

• P. johnsonii abundance negatively correlated with blood glucose and lipid levels in obese patients.
• Oral P. johnsonii improved metabolic dysfunction, reduced leaky gut, and systemic inflammation in mice.
• P. johnsonii enhanced branched-chain amino acid catabolism to branched-chain short-chain fatty acids (BSCFAs), particularly valine to isobutyrate.
• Isobutyrate mimicked P. johnsonii's effects, increasing H3K14 acetylation and FGF1B transcription via HDAC3 inhibition, improving intestinal barrier.
• Stachyose promoted P. johnsonii growth and exhibited anti-obesity effects.

Conclusions:

• P. johnsonii demonstrates significant therapeutic potential for metabolic disorders.
• Isobutyrate mediates P. johnsonii's beneficial effects on gut barrier integrity and metabolism.
• Stachyose may be a prebiotic enhancing P. johnsonii for metabolic health.