Cell-free probiotic supernatant (CFS) treatment alleviates indomethacin-induced enterocolopathy in BALB/c mice by down-modulating inflammatory response and oxidative stress: potential alternative targeted treatment

Probiotics and their metabolites appear to be a promising approach that targets both the intestinal inflammation and dysbiosis in bowel diseases. In this context, the emergence of the probiotic cell-free supernatant (CFS) has attracted more attention as a safe and targeted alternative therapy with reduced side effects. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause significant intestinal alterations and inflammation, leading to experimental enterocolopathy resembling Crohn disease. Therefore, we investigated the effect of CFS supplementation on the inflammation and the mucosal intestinal alterations induced by NSAIDs, indomethacin. In the current study, a murine model of intestinal inflammation was generated by the oral gavage (o.g) of indomethacin (10 mg/kg) to BALB/C mice. A group of mice treated with indomethacin was concomitantly treated orally by CFS for 5 days. The Body Health Condition index was monitored, and histological scores were evaluated. Moreover, oxidative and pro-inflammatory markers were assessed. Interestingly, we observed that CFS treatment attenuated the severity of the intestinal inflammation in our enterocolopathy model and resulted in the improvement of the clinical symptoms and the histopathological features. Notably, nitric oxide, tumor necrosis factor alpha, malondialdehyde, and myeloperoxidase levels were down-modulated by CFS supplementation. Concomitantly, an attenuation of NF-κB p65, iNOS, COX2 expression in the ileum and the colon was reported. Collectively, our data suggest that CFS treatment has a beneficial effect in experimental enterocolopathy model and could constitute a good therapeutic candidate for alleviating inflammatory responses and to maintain mucosal homeostasis during chronic and severe conditions of intestinal inflammation.