Effect of Lactobacillus ingestion on the gastrointestinal mucosal barrier alterations induced by indometacin in humans

Background: Chronic nonsteroidal anti-inflammatory drug (NSAID) ingestion strongly affects the gastrointestinal mucosa as a first stage before ulceration. Some Lactobacillus strains may stabilize the mucosal barrier by increasing mucin expression, reducing bacterial overgrowth, stimulating mucosal immunity and synthetizing antioxidant substances; these events are altered in NSAID-associated gastroenteropathy. Aim: To determine whether ingestion of the probiotic Lactobacillus GG (LGG) protects the gastrointestinal mucosa against indometacin-induced alterations of permeability. Subjects and methods: Four gastrointestinal permeability tests were carried out in random order in 16 healthy volunteers: (i) basal; (ii) after indometacin; (iii) after 5 days of living LGG ingestion before indometacin administration; (iv) after 5 days of heat-killed LGG ingestion before indometacin administration. Results: Indometacin significantly increased basal sucrose urinary excretion (29.6 mg [17.1-42.1] vs. 108.5 mg [68.2-148.7], P=0.0030) (means [95% CI]) and lactulose/mannitol urinary excretion (1.03% [0.73-1.32] vs. 2.93% [1.96-3.90], P=0.00012). Heat-killed LGG did not modify the indometacin-induced increase of gastrointestinal permeability, while live bacteria significantly reduced the alteration of gastric (47.8 mg [31.1-64.6], P=0.012) but not intestinal permeability induced by NSAID. Conclusions: Regular ingestion of LGG protects the integrity of the gastric mucosal barrier against indometacin, but has no effect at the intestinal level.