The Role of Intestinal Bacteria, Bacterial Translocation and Endotoxin in Dextran Sodium Sulphate-Induced Colitis in the Mouse

Abstract

Experimental inflammation of the large intestine can be induced in mice by oral administration of dextran sodium sulphate (DSS) given in the drinking water. This inflammation has been considered to require the presence of a normal microbiota. We have earlier shown that germ-free (GF) mice are susceptible to DSS-induced intestinal inflammation. To further investigate the relative importance of bacteria in this model we induced DSS-intestinal inflammation in GF mice, in mice with a restricted microbiota, and in mice with a conventional microbiota. In addition we used mice which are resistant to endotoxin. It was shown that the intestinal inflammation in GF mice and conventional bacteria associated mice had a similar histological appearance and anatomical localisation. In mice with a restricted microbiota, endotoxin measurements of serum samples showed that varying endotoxin levels could be found in healthy animals as well as in animals with DSS-induced intestinal inflammation. Bacteriological investigations of organs such as the lung, liver, spleen, mesenterial lymph nodes and blood were performed and no bacteria were found in healthy mice. In diseased mice varying amounts of bacteria were found but did not conform to the mortality in these mice. The endotoxin receptor-deficient C3H/HeJ mice given DSS showed the same mortality as conventional C3H/HeN mice. It was concluded that neither bacterial translocation from the intestine nor systemic endotoxin has a crucial role in the mortality seen in severe cases of DSS-induced intestinal inflammation.

Key Words:

• disease models
• mice
• ulcerative colitis
• dextran sulphate
• endotoxin