Pyocyanin Modulates Gastrointestinal Transformation and Microbiota

Phenazines are ubiquitously produced by Pseudomonas spp. in the environment and are widely used in agriculture and clinical therapies, making their accumulation through the food chain cause potential risks to human health. Here, we utilized pyocyanin (PYO) as a representative to study the effects of phenazines on digestive tracts. Pharmacokinetic analysis showed that PYO exhibited low systemic exposure, slow elimination, and low accumulation in both rat and pig models. PYO was subsequently found to induce intestinal microbiota dysbiosis, destroy the mucus layer and physical barrier, and even promote gut vascular barrier (GVB) impairment, consequently increasing the gut permeability. Additionally, integral and metabolomic analyses of the liver demonstrated that PYO induced liver inflammation and metabolic disorders. The metabolic analysis further confirmed that all of the metabolites of PYO retain the nitrogen-containing tricyclic structural skeleton of phenazines, which was the core bioactivity of phenazine compounds. These findings elucidated that PYO could be metabolized by animals. Meanwhile, high levels of PYO could induce intestinal barrier impairment and liver damage, suggesting that we should be alert to the accumulation of phenazines.

Automated summary

Phenazines, widely produced by Pseudomonas spp. and used in agriculture and clinical therapies, can potentially pose risks to human health through accumulation in the food chain. This study focused on the effects of pyocyanin as a representative phenazine on the digestive tracts. The results showed that pyocyanin could disrupt the intestinal microbiota, damage the mucus layer and physical barrier, and increase gut permeability. Furthermore, it induced liver inflammation and metabolic disorders.