NSAID enteropathy and bacteria: a complicated relationship.

The clinical significance of small intestinal damage caused by nonsteroidal anti-inflammatory drugs (NSAIDs) remains under-appreciated. It occurs with greater frequency than the damage caused by these drugs in the upper gastrointestinal tract, but is much more difficult to diagnose and treat. Although the pathogenesis of NSAID enteropathy remains incompletely understood, it is clear that bacteria, bile, and the enterohepatic circulation of NSAIDs are all important factors. However, they are also interrelated with one another. Bacterial enzymes can affect the cytotoxicity of bile and are essential for enterohepatic circulation of NSAIDs. Gram-negative bacteria appear to be particularly important in the pathogenesis of NSAID enteropathy, possibly through release of endotoxin. Inhibitors of gastric acid secretion significantly aggravate NSAID enteropathy, and this effect is due to significant changes in the intestinal microbiome. Treatment with antibiotics can, in some circumstances, reduce the severity of NSAID enteropathy, but published results are inconsistent. Specific antibiotic-induced changes in the microbiota have not been causally linked to prevention of intestinal damage. Treatment with probiotics, particularly Bifidobacterium, Lactobacillus, and Faecalibacteriaum prausnitzii, has shown promising effects in animal models. Our studies suggest that these beneficial effects are due to colonization by the bacteria, rather than to products released by the bacteria.

Environmental and NSAID-enteropathy: dysbiosis as a common factor.

At first sight, environmental enteropathy and NSAID enteropathy may appear to have little in common. One occurs almost exclusively in poor countries and the other primarily in rich countries. One is the consequence of unhygienic living conditions, while the other is a consequence of use of a drug for relief of pain and inflammation. However, there may be a common pathogenic link between these two conditions, namely a significant alteration in the microbiome (dysbiosis), and this raises the possibility of common approaches to treatment. Correction of the dysbiosis that is central to the intestinal tissue injury and dysfunction observed in environmental and nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathies is a logical approach to bringing about restoration of intestinal function. For both conditions, removal of the trigger for dysbiosis is the simplest approach, but is not always feasible. Correcting the underlying dysbiosis through the use of probiotics or prebiotics may be a viable option.