Multi-strain Probiotics for Treatment of Necrotizing Enterocolitis in Preterm Rats: Histological and Immunohistochemical Evaluation.

Necrotizing enterocolitis (NEC) is a commonly encountered disease of the gastrointestinal tract in premature infants. The aim of the study was to evaluate the therapeutic role of probiotics on NEC in a preterm rat model. NEC model was induced in preterm formula-fed rats, exposed daily to hypoxia, hypothermia, and administered pathogenic bacteria. Then rats were randomly divided into four different groups: control group, NEC group, NEC-antibiotic group, and NEC-probiotic group. All rats were sacrificed at the end of the experiment. Histological examination of ileal wall under light and electron microscopes was done, and TNF-α and IL-18 staining was also assessed. Statistical analysis of data was performed. Histological examination of the ileal mucosa of NEC group showed inflammatory infiltration, various degrees of separation of the submucosa, thinning of the wall, sloughing, and loss of the intestinal villi. The villus heights significantly decreased (p ≤ 0.05) in the NEC group. Electron micrographs demonstrated signs of enterocytic death, lost microvilli, abnormal nuclei, vacuolated cytoplasm, swollen mitochondria, and loss of junctional complexes. These findings were almost reversed in the probiotic group that regained the normal villous height, and to a lesser extent in the antibiotic group which was still significant compared to the CG (p ≤ 0.05). Immunohistochemical staining showed significantly increased expression of proinflammatory cytokines TNF-α and IL-18 (p ≤ 0.05) in the intestinal mucosa of the NEC group and NEC-antibiotic group as compared to the control group and the NEC-probiotic group. Probiotics could hold therapeutic potential for NEC in preterm neonatal rats.