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

BACKGROUND AND PURPOSE: The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be associated with severe adverse digestive effects. The aim of this study was to examine the protective effects of the probiotic S. boulardii CNCM I-745 in a rat model of diclofenac-induced enteropathy.

EXPERIMENTAL APPROACH: Enteropathy was induced in 40-wk-old male rats by intragastric diclofenac (4 mg/kg BID for 14 days). S. boulardii CNCM I-745 (3 g/kg BID by oral gavage) was administered starting 14 days before (preventive protocol) or in concomitance (curative protocol) with diclofenac administration. Ileal damage, inflammation, barrier integrity, gut microbiota composition, and TLRs-NF-kB-pathway were evaluated.

KEY RESULTS: Diclofenac elicited intestinal damage, along with increments of myeloperoxidase, malondialdehyde, tumor necrosis factor and interleukin-1β, overexpression of TLR-2/-4, MyD88, and NF-kB p65, increased faecal calprotectin and butyrate levels as well as a decrease in blood hemoglobin levels, occludin and butyrate transporter 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 protocol, 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. No significant changes were observed for the occludin expression after probiotic treatment.

CONCLUSION 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.