A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ-free rats.

The effects of indomethacin and ibuprofen on gastrointestinal mucosal integrity were studied in conventional and germ-free rats. Only ibuprofen induced significant gastric erosion formation in both conventional and germ-free animals, demonstrating that the presence of micro-organisms is not required in this form of damage. Both indomethacin and ibuprofen caused significant intestinal damage and blood loss in germ-free animals. However, in the conventional counterparts, damage due to indomethacin was enhanced whereas that induced by ibuprofen was not. The results from the present work would suggest that non-steroidal anti-inflammatory drugs such as indomethacin, which are secreted largely in the bile, unlike ibuprofen, may act in concert with bacteria and the constituents of bile to induce, in part, intestinal damage and blood loss.

Effect of dietary arginine on urinary nitrate excretion in germ-free rats.

The effect of dietary arginine on the endogenous synthesis of nitrate in germ-free rats was investigated. The animals were fed, for up to 18 days, purified diets containing either casein or lactalbumin (proteins differing in arginine content) with or without additional free arginine. Urine was collected from all animals for 4 days, and the animals were then dosed ip with Escherichia coli lipopolysaccharide (LPS) to stimulate nitrate synthesis and urine collected for a further 4 days. The urine samples were analysed for nitrate by ion chromatography. Although the excretion of nitrate was markedly stimulated by LPS treatment, there were no significant effects of protein source or arginine supplementation of the diet.

Rat intestinal mucosal responses to a microbial flora and different diets.

The effects of diet on the histochemical composition of intestinal mucosubstances and the morphology of the villi and crypts were investigated by comparing the data of germ free and conventionally maintained rats fed either a purified diet or a commercial diet. The influence of intestinal microflora was evaluated by comparing the germ free rats and those harbouring either a conventional rat flora or a human microbial flora. In both germ free rats and those maintained conventionally, feeding a purified diet resulted in shallower crypts in the small intestine but deeper crypts in the large intestine compared with their counterparts fed on the commercial diet. The preliminary data obtained with association of human flora showed a reduction of the villus height and crypt depth in the small intestine and, to some extent, the amount of neutral mucins in the goblet cells of both small and large intestine and an increase in the amount of sulphated mucins in the large intestine. In rats given the commercial diet the periodic acid Schiff staining for neutral mucins was more intense in the upper crypts of the small intestine than in the lower crypts, and to a lesser extent in the upper crypts of the large intestine. These results provide evidence that the dietary composition, microbial flora, as well as the interactions between the dietary constituents and microbial flora change the mucosal architecture and the mucus composition and therefore alter the functional characteristics of the intestinal tract.