Rats were orally treated with vehicle or Bifidobacterium longum subsp. Adolescentis (BA), a low acetate producer, or B. longum subsp. longum (BL), a high acetate producer (both at 109 CFU), for 9 days. In addition, two isogenic strains were also tested: a second BL strain (BN) and its derivative (BNKO) in which a gene deletion results in low acetate production. Naproxen (20 mg/kg) was co‐administered on the final 4 days, then small intestinal damage was blindly scored.Treatment with BA decreased naproxen‐induced intestinal damage by 82%; p<0.05, while BL exerted no effect. BN reduced damage by 75% (p<0.05), and a similar beneficial effect was observed with the low acetate‐producing knockout bacterium, BNKO (62% reduction; p<0.05).Small intestinal injury by NSAIDs is a serious clinical problem, with no available treatments. Acetate production by these Bifidobacterium strains does not appear to be important for prevention of NSAID‐enteropathy, given that a high acetate producing Bifidobacteria (BL) exhibited no protective effect, while a low acetate‐producing mutant (BNKO) was as effective in reducing damage as another high acetate‐producing bacterium (BN).