Probiotic Saccharomyces boulardii attenuates cardiopulmonary bypass-induced acute lung injury by inhibiting ferroptosis.

OBJECTIVE

Acute lung injury (ALI) is one of the most common and fatal complications of cardiopulmonary bypass (CPB). Probiotics treatment has been shown to reduce lung injury in different experimental models. However, the effect of probiotics on CPB-induced ALI is still poorly understood. This study aimed to investigate whether probiotic CNCM I-745 treatment protects against lung injury in a rat model of CPB.

METHODS

Rats were orally gavaged with CNCM I-745 once a day for 5 days before being subjected to CPB. Rats were euthanized post-CPB, and samples of lung tissue were processed for later investigation. The levels of inflammatory cytokines were measured by ELISA. The expression levels of ferroptosis markers in lungs were assessed by western blot. The microbes in feces and proximal colon of rats were analyzed by using 16S rDNA amplicon sequencing method. The ratio and maturity of conventional dendritic cells (cDCs) were determined by flow-cytometry.

RESULTS

CNCM I-745 treatment improved lung function, attenuated pathologic lung changes and decelerated the exacerbation of inflammatory cytokine level after experimental CPB. CNCM I-745 treatment also inhibited CPB-induced ferroptosis, as evidenced by the changes of main markers of ferroptosis, namely, the increase of Glutathione peroxidase 4 (GPX4) and the decrease of Acyl-CoA synthetase long chain family member 4 (ACSL4). In addition, after CNCM I-745 treatment, the ratio and maturity of conventional dendritic cells (cDCs) in the guts of rats with CPB were significantly up-regulated.

CONCLUSION

Our findings suggest that probiotic CNCM I-745 reduces CPB-induced lung injury through suppression of the ferroptosis in lung and up-regulation of the ratio and maturity of cDCs in gut.