Pyocyanin Modulates Gastrointestinal Transformation and Microbiota

Area of Science:

• Microbiology
• Toxicology
• Environmental Science

Background:

• Phenazines are microbial compounds with agricultural and clinical uses.
• Environmental accumulation of phenazines poses potential human health risks.
• Pyocyanin (PYO) serves as a model compound to study phenazine effects.

Purpose of the Study:

• To investigate the toxicological effects of phenazines, using PYO, on animal digestive tracts.
• To assess the pharmacokinetic behavior and metabolic fate of PYO in vivo.
• To elucidate the impact of PYO on intestinal barrier function and liver health.

Main Methods:

• Pharmacokinetic analysis in rat and pig models.
• Assessment of intestinal microbiota and barrier integrity.
• Liver integral and metabolomic analyses.
• Metabolite structural analysis.

Main Results:

• PYO showed low systemic exposure, slow elimination, and minimal accumulation.
• PYO induced intestinal microbiota dysbiosis, mucus layer destruction, and increased gut permeability.
• PYO impaired the gut vascular barrier (GVB).
• PYO caused liver inflammation and metabolic disorders.
• PYO metabolites retained the core phenazine structural skeleton, indicating metabolism by animals.

Conclusions:

• Phenazines like PYO are metabolized by animals but can induce significant intestinal barrier impairment and liver damage at high concentrations.
• Alertness to phenazine accumulation is warranted due to observed toxicity.
• Findings highlight potential risks associated with environmental phenazine exposure.