Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy Original paper

What was studied?

This clinical study investigated whether metronidazole can reduce intestinal inflammation and blood loss in patients with non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. The researchers designed a prospective trial involving 13 patients with confirmed NSAID enteropathy and assessed key markers of gastrointestinal damage before and after a 2–12-week course of oral metronidazole (800 mg/day). They evaluated changes in intestinal permeability, fecal excretion of radiolabeled neutrophils (to assess inflammation), labeled red blood cell loss (to quantify GI bleeding), and gastroduodenal endoscopy findings.

Who was studied?

The investigators enrolled thirteen adult patients with rheumatoid or osteoarthritis who had been taking NSAIDs for more than six months and had documented NSAID-induced small intestinal inflammation. These individuals continued their NSAID therapy unchanged during the study period. The researchers used healthy volunteers and patients with irritable bowel syndrome as controls for baseline measurements of permeability and blood loss. All subjects gave informed consent and underwent rigorous inpatient evaluation, including endoscopy, leukocyte and red blood cell radiolabeling, and urinary permeability testing.

What were the most important findings?

The study found that metronidazole significantly reduced intestinal inflammation and blood loss in patients with NSAID enteropathy. After treatment, fecal excretion of indium-111-labeled neutrophils dropped from a mean of 4.7% to 1.5% (p <0.001), and mean daily gastrointestinal blood loss fell from 2.6 mL/day to 0.9 mL/day (p <0.01). These improvements occurred without significant changes in intestinal permeability, suggesting that metronidazole targets the inflammatory cascade rather than the primary permeability defect. Endoscopic and histological examinations of the gastroduodenal mucosa revealed no consistent changes, further pointing to the small intestine as the main site of injury.

The authors proposed that a metronidazole-sensitive microbe, likely anaerobic, may play a central role in attracting neutrophils to the intestinal mucosa, initiating tissue damage and bleeding. While the exact organism remains unidentified, the study supports the theory that NSAID-induced changes in permeability allow microbial antigens to invade the lamina propria, triggering neutrophil activation. From a microbiome perspective, this implicates the anaerobic community in NSAID-associated inflammation, possibly involving species from the Bacteroides or Clostridium genera, which are susceptible to metronidazole.

This research aligns with broader microbiome literature suggesting that NSAIDs promote dysbiosis and barrier dysfunction. By selectively reducing neutrophil-driven damage, metronidazole may modulate microbial-immune interactions, although this benefit must be weighed against its known microbiome-disruptive effects.

What are the implications of this study?

This study offers critical insights for clinicians managing patients with NSAID enteropathy. By demonstrating that metronidazole can mitigate intestinal inflammation and bleeding without altering gut permeability, the researchers highlight its potential as a microbiome-targeted intervention during flare-ups or in cases of refractory anemia or hypoalbuminemia. For microbiome-focused practice, the findings underscore the role of gut bacteria in perpetuating enteropathy. This positions metronidazole as both a microbiome modulator and a clinical therapeutic, capable of interrupting a host-microbe inflammatory feedback loop in the small intestine. However, its use must be judicious, given the risks of peripheral neuropathy and microbiome disruption with long-term administration.