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

Abstract

Background and PurposeThe 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 ApproachEnteropathy 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 ResultsDiclofenac 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 ImplicationsTreatment 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.

Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools

“…The unrestrained increase in the use of NSAIDs over the years is still controversial, since there are an escalating incidences of toxicity [ 17 ]. Unexpectedly, adverse gastrointestinal reactions, including occult bleeding, so-called enteropathy [ 18 ], kidney failure [ 19 ], and liver damage [ 20 ], were reported to be the most pervasive and unavoidable side effects of the prolonged consumption of NSAIDs, putting people all over the world in jeopardy. Notably, the alarming spread of adverse toxicity in certain segments of the population, the high cost, and the upsurge in drug resistance are three specific hindrances to increasing the use of NSAIDs, which are becoming less supportive with a narrow safety window.…”