Ozone controls the metabolism of tryptophan protecting against sepsis-induced intestinal damage by activating aryl hydrocarbon receptor.

BACKGROUND

Intestinal injury is the most common complication of sepsis, and the mitigation of intestinal damage is crucial for treating sepsis.

AIM

To examine the use of ozone-rich water and its action in preventing intestinal damage caused by sepsis.

METHODS

Through histological analysis, immunohistochemistry, immunofluorescence assays, and Western blot detection, we evaluated the therapeutic efficacy of ozone in mitigating intestinal injury during sepsis. Additionally, by conducting 16S rRNA sequencing and untargeted metabolomics analysis on fecal samples, we identified alterations in the gut microbiota and specific metabolites in septic mice following ozone treatment. This comprehensive approach aims to further elucidate the mechanistic underpinnings of ozone therapy in alleviating sepsis-induced intestinal damage.

RESULTS

Our results demonstrate that ozonated water significantly ameliorates pathological damage in intestinal tissues, enhances the expression of tight junction proteins, and inhibits the polarization of intestinal macrophages, thereby reducing the expression of inflammatory cytokines in intestinal tissues of cecal ligation and puncture-induced septic mice. 16S rRNA sequencing analysis revealed that ozonated water increased the abundance of beneficial bacteria and alleviated gut microbiota dysbiosis. Studies using broad-spectrum antibiotic-treated mice indicated that the protective effects of ozonated water on intestinal injury are dependent on the gut microbiota. Furthermore, metabolomic analysis identified an increase in the tryptophan metabolite DL-tryptophan in the ozonated water treatment group. This suggests that ozonated water protects against intestinal injury by activating the aryl hydrocarbon receptor and suppressing necroptosis in intestinal epithelial cells.

CONCLUSION

Ozone protected against sepsis-induced intestinal injury through regulation of the gut microbiota and tryptophan metabolism, inhibiting necrotic apoptosis of intestinal epithelial cells through activation of the aryl hydrocarbon receptor.