Pyocyanin Modulates Gastrointestinal Transformation and Microbiota

Abstract

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.

Dietary lead modulates the mouse intestinal microbiome: Subacute exposure to lead acetate and lead contaminated soil

“…Phenazine and angucycline related compound genes can be plasmid linked ( Novakova et al, 2013 ; Rui et al, 2012 ) so co-occurrence with metal resistance genes is possible, however generally not reported in the intestinal tract. However, the phenazine compound pyocyanin, when introduced into the intestinal tract, does modulate both the intestinal flora and metabolism ( Peng et al, 2022 ).…”

The two faces of pyocyanin - why and how to steer its production?

“…Li et al (2018) also reported that PYO is well-tolerated by probiotic microorganisms (Lactobacillus spp.). However, considering an opposing conclusion made by Peng et al (2022) who indicated that PYO may be detrimental to the function of intestinal microbiota, it appears that further experimental investigations still have to be carried out. Regarding humans, the current data cannot exclude that ingesting PYO will cause adverse effects.…”

“…However, higher concentrations resulted in opposite observations. Peng et al (2022) analysed the influence of PYO on mice and pig digestive tracts. The authors proved that PYO exposure led to dysbiosis of microbiota and damage to the mucus layer.…”

Metal complexes with valuable biomolecules produced by Pseudomonas aeruginosa: a review of the coordination properties of pyocyanin, pyochelin and pyoverdines

“…3,4 Due to the broad-spectrum antimicrobial activity against various bacterial and fungal pathogens, several phenazines, such as phenazine-1-carboxylic acid and phenazine 5-oxide, have been approved as pesticides in agricultural crops. 5,6 Phenazines have low molecular weight and zwitterionic properties, allowing them to easily penetrate cell membranes and cross through the blood–brain barrier, resulting in cell damage. 7 Moreover, the redox-active tricyclic zwitterion forms reactive oxygen species (ROS), a process which can influence the cardiovascular, respiratory, urological, and central nervous systems.…”