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.