Use of Saccharomyces boulardii CNCM I‐745 as therapeutic strategy for prevention of nonsteroidal anti‐inflammatory drug‐induced intestinal injury

Abstract Background and Purpose Nonsteroidal anti‐inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. This study examined the protective effects of the probiotic Saccharomyces boulardii CNCM I‐745 in a rat model of diclofenac‐induced enteropathy. Experimental Approach Enteropathy was induced in 40‐week‐old male rats by intragastric diclofenac (4 mg·kg −1 BID for 14 days). S. boulardii CNCM I‐745 (3 g·kg −1 BID by oral gavage) was administered starting 14 days before (preventive protocol) or along with (curative protocol) diclofenac administration. Ileal damage, inflammation, barrier integrity, gut microbiota composition and toll‐like receptors (TLRs)–nuclear factor κB (NF‐κB) pathway were evaluated. Key Results Diclofenac elicited intestinal damage, along with increments of myeloperoxidase, malondialdehyde, tumour necrosis factor and interleukin‐1β, overexpression of TLR2/4, myeloid differentiation primary response 88 (Myd88) and NF‐κB p65, increased faecal calprotectin and butyrate levels, and decreased blood haemoglobin levels, occludin and butyrate transporter monocarboxylate transporter 1 (MCT1) expression. In addition, diclofenac provoked a shift of bacterial taxa in both faecal and ileal samples. Treatment with S. boulardii CNCM I‐745, in both preventive and curative protocols, counteracted the majority of these deleterious changes. Only preventive administration of the probiotic counteracted NSAID‐induced decreased expression of MCT1 and increase in faecal butyrate levels. Occludin expression, after probiotic treatment, did not significantly change. Conclusions and Implications Treatment with S. boulardii CNCM I‐745 prevents diclofenac‐induced enteropathy through anti‐inflammatory and antioxidant activities. Such effects are likely to be related to increased tissue butyrate bioavailability, through an improvement of butyrate uptake by the enteric mucosa.