Non-steroidal anti-inflammatory drugs-induced small intestinal injury and probiotic agents

Abstract

Intestinal bacteria play a role in the development of non-steroidal anti-inflammatory drugs (NSAID)-induced small intestinal injury. Agents such as probiotics, able to modify the gut ecology, might theoretically be useful in preventing small intestinal damage induced by NSAIDs. The clinical studies available so far do suggest that some probiotic agents can be effective in this respect.

Key Words: Non-steroidal anti-inflammatory drugs; Small intestine; Intestinal bacteria; Probiotics

TO THE EDITOR

Park et al[1,2] in their interesting editorial[1] about small intestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs), discussed the possible role of the intestinal flora in the pathogenesis of the enteric damage, but, oddly enough, when listing the pharmacological agents theoretically useful as protective or therapeutic medicines, they omitted to mention probiotics. Live micro-organisms could prevent NSAID-induced small intestinal damage by both modifying intestinal microbial ecology and modulating the local immune function.

Various studies have addressed the issue. While a pilot study in human volunteers failed to demonstrate any effect of Lactobacillus GG in preventing indomethacin-induced alterations of intestinal permeability[3], a subsequent experimental study demonstrated that in rats pre-treated with Lactobacillus casei, strain Shirota significantly prevents the development of indomethacin-induced enteropathy[4], although the mechanism responsible for this phenomenon remains not completely clear.

In a recent trial, patients treated for three months with low-dose enteric-coated aspirin (100 mg daily) were randomized to receive either co-administration of Lactobacillus casei or no additional treatment[5]. Capsule endoscopy, performed before and after treatment, showed a significant decrease (P = 0.039) in the number of mucosal breaks and in the endoscopic score in the probiotic group as compared with controls.

In a randomized, double-blind, cross-over placebo-controlled study in healthy volunteers, the probiotic mixture VSL # 3 was found to prevent the increase in faecal concentration of the inflammatory marker calprotectin during intake of indomethacin 50 mg daily[6].

The role of bacteria in the development of small intestinal lesions during NSAID administration seems indirectly confirmed, but the recent experimental observations showed that proton pump inhibitors significantly worsen intestinal ulcerations and bleeding in naproxen- and celecoxib-treated rats and this is related to substantial shifts in enteric microbial population (e.g., a marked reduction in Actinobacteria and Bifidobacteria)[7].

All in all, it appears that probiotics can represent promising agents in the prevention of NSAID-induced small intestine injury, although additional studies are needed to better clarify this point. However, the efficacy of any single probiotic strain should be evaluated separately, due to the differences in the biological effects and mode of actions of the various agents currently available.