Postbiotic effect of Escherichia coli CEC15 and Escherichia coli Nissle 1917 on amurine model of 5-FU-induced intestinal mucositis

Abstract

Abstract Postbiotics are preparations of inanimate microorganisms and/or their components that confers a health benefit on the host. The Escherichia coli strains Nissle 1917 (EcN) and CEC15 have shown beneficial effects, in their live form, in murine models of intestinal inflammation, such as colitis and mucositis. However, the use of live bacteria, in special by immunocompromised individuals, had raised concerns. Based on this, the present study evaluated the effects as postbiotic of heat-inactivated, and cell-free supernatant preparations of EcN and CEC15 in attenuating 5-fluorouracil (5-FU)-induced intestinal mucositis in mice and compared them with the probiotic effects of the live preparations. BALB/c mice were fed daily, by gavage, with 1010 CFU of live or inactivated bacteria, or with 300 µL of cell-free supernatant for 12 days. On the 10th day, all animals, except for the control group, received an intraperitoneal injection of 5-FU (300 mg/kg). After 72 h of 5-FU administration, animals were euthanized, and the ileum and blood were collected for analysis. Treatments with live and heat-inactivated CEC15 mitigated weight loss, preserved intestinal length, reduced histological damage, maintained goblet cells, decreased neutrophil infiltration, and modulated expression of inflammatory and barrier genes, when compared to 5-FU mucositis controls. EcN showed more limited effects. CEC15 upregulated mRNA expression of the mucin MUC2 and tight junction protein TJP1. Overall, CEC15 demonstrated protective effects against 5-FU-induced mucositis, whatever the way it was administered: live bacteria, heat-inactivated bacteria, or cell-free supernatant. This suggests CEC15 mediates a protective response via secreted metabolites and does not require viability.