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HIGH LACTATE-PRODUCING BIFIDOBACTERIA AS A POTENTIAL PROPHYLACTIC THERAPY FOR NSAID-ENTEROPATHY
S Syer1, G McKnight1, P Langella2, A Aucouturier2, R Martin2, J Wallace11McMaster University, Hamilton, ON; 2INRA, Jouy en Josas, France
Aims: For patients chronically treated with nonsteroidal anti-inflammatory drugs (NSAIDs), the risk of GI ulceration and bleeding is common and potentially serious. Such damage occurs in the small intestine more frequently than previously recognized, likely with a different pathogenesis than the gastric damage induced by NSAIDs. There is clear evidence for a crucial role of enteric bacteria (particularly gram-negative) in NSAID-enteropathy. We recently demonstrated that suppression of gastric acid secretion with proton pump inhibitors (PPIs) exacerbates NSAID-enteropathy by altering the small intestinal flora; specifically, PPIs cause a diminution of intestinal levels of Bifidobacteria (Wallace et al. 2011). Here we examined the possibility that treatment with Bifidobacteria would protect the intestine from NSAID-damage. We further attempted to determine if the ability of Bifidobacteria to produce lactate was important in any observed protective effect, given that lactate has recently been shown to reduce NSAID-induced intestinal damage in rats (Watanabe et al. 2009).
Methods: Rats (n >=5 per group) were orally treated with vehicle, Bifidobacterium adolescentis DSM20219 (BA; high lactate-producing) or Bifidobacteria longum DSM 20083(BL; low lactate-producing) at various concentrations once-daily for nine days. During the final four days, the rats were treated orally, twice-daily, with an anti-inflammatory dose of naproxen (10 mg/kg). Small intestinal damage was blindly scored at the end of the treatment period. Samples of cecum and small intestine were taken for PCR analysis of the microbiota. To determine if general increases in Actinobacteria could be protective against NSAID enteropathy, groups of rats (n >=5 per group) were given drinking water supplemented with 1% inulin (from chicory) starting one week prior to, and continuing during naproxen administration.
Results: BA , but not BL (both at 109 CFU), significantly reduced naproxen-induced small intestinal damage as compared to controls. There was an ~82% decrease in intestinal damage when BA treated animals compared to controls (P=0.02). Rats given water supplemented with inulin exhibited naproxen-induced small intestinal damage comparable in severity to that seen in controls.
Conclusions: A lactate-producing species of Bifidobacteria significantly reduced the severity of NSAID-enteropathy in rats, while a species of Bifidobacteria not producing lactate had no effect. Similarly, inulin, which has been shown to increase intestinal Bifidobacteria levels, did not attenuate NSAID-enteropathy. This suggests that lactate production is a key factor in the beneficial effects observed with Bifidobacteria. Lactate-producing Bifidobacteria may represent a viable prophylactic therapy for NSAID-enteropathy.