THE POTENTIAL IMMUNOMODULATING CAPACITY AND PROTECTIVE ROLE OF PROBIOTICS AGAINST INTESTINAL BARRIER FAILURE IN EXPERIMENTAL CIRRHOSIS

Probiotics are now used in many countries for prevention and treatment of some diseases. Liver cirrhosis induces intestinal mucosal barrier dysfunction and impairs mucosal defences against luminal bacteria. This work aims to study the histological changes in the intestine of cirrhotic rats and to determine the ability of Lactobacillus casei (L. casei) as a probiotic to immune-modulate or prevent cirrhosis-induced intestinal changes. Twenty seven adult rats were used in this study and classified into 3 groups: 9 rats were used as control, 9 were injected i.p. with CCI4 (0.2ml/100 g/ b.w. twice weekly for 12 weeks) to induce cirrhosis, and 9 animals received 0.5 ml of L. casei prepared suspension orally ten days before CCU injection and continued for 12 weeks during injection. Sera from all animals were tested for tumour necrosis factor-alpha (TNF-a) and interferon-gamma (INF-y). Also, intestinal segments from each animal were examined histologically by using light and electron microscopes. In cirrhotic rats (group II) TNF-a was increased significantly while INF-y showed non-significant increase as compared with the control. Histologically, the intestine showed degenerated lining epithelium and increased thickness of submucosa. PAS-stained sections showed apparently decreased goblet cells number and decreased in reactivity of the brush border. Ultrastructurally, the intestinal columnar cells showed degenerated microvilli, wide intercellular spaces, dilated rER, swollen mitochondria, shrunken irregular nuclei and many secondary lysosomes. In group III, TNF-a was increased non-significantly while IFN-y showed a significant increase. Histologically, the intestinal villi appeared normal with intact lining epithelium except few areas that were slightly affected. Except for mild rER dilatation and presence of few secondary lysosomes, most of enterocytes organelles appeared normal. Also, the brush border of the intestinal epithelium and goblet cells maintained their normal PAS-positive reaction. These results support L. casei as a good probiotic in preventing intestinal mucosal damage associated with cirrhosis. These effects may be mediated by immunomodulation through TNF-a and IFN-y