Protective effects of Saccharomyces boulardii CNCM I-745 Against Nonsteroidal anti-inflammatory drug-induced intestinal injury

Introduction The use of nonsteroidal anti-inflammatory drugs (NSAIDs) can induce gastrointestinal detrimental effects. There is evidence that NSAIDs could elicit an impairment of intestinal epithelial barrier (IEB) integrity associated with gut dysbiosis, thus favouring the development of mucosal inflammation and injury. Aims & Methods The aim of this study was to examine the protective effects of the probiotic yeast S. boulardiiCNCM I-745 (Biocodex, France) in a rat model of diclofenac-induced enteropathy. 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. At the end of treatments, the ileum was processed for the metagenomic analysis of residing bacterial populations and evaluation of interleukin (IL)-1β levels, as well as for the expression of the tight junction protein occludin and butyrate transporter MCT1. In addition, fecal levels of short chain fatty acids (SCFAs) propionate and butyrate as well as metagenomic analysis of bacteria in the feces were also assessed. Results Diclofenac elicited intestinal inflammation, triggering an increase in tissue concentrations of IL-1β. Moreover, the NSAID induced a decrease in ileal occludin and MCT1 expression and an increase in fecal butyrate levels. Diclofenac also provoked a shift of bacterial taxa in both faecal (higher abundance of Lachnospiraceae) and ileal samples (increased Enterococcus and Staphylococcusand decreased Lactobacillus). The curative protocol elicited several variations in the microbiota composition compared to treatment with diclofenac, such as the reduction of Enterococcus in both faecal and ileal samples, along with an increase in Pediococcus abundance in stool and in Bifidobacterium, Ruminococcus, and Roseburia in the ileum. Preventive treatment also lowered Enterococcus abundance in both biological samples, additionally increasing Pediococcus and Lachnospiraceae in faeces and reducing Staphylococcus in the ileum. Of interest, only preventive administration of the probiotic counteracted NSAID-induced decreased expression of MCT1 and increase in fecal butyrate levels. No significant changes were observed for the occludin expression after treatment with S. boulardii CNCM I-745 in both preventive and curative protocol. Conclusion Treatment with S. boulardii CNCM I-745, in both preventive and curative protocol, partially reverted the diclofenac-induced shift of bacterial community composition. In addition, treatment with S. boulardii CNCM I-745 exerted beneficial effects on tissue butyrate bioavailability, typically altered in inflammatory conditions. Such positive effect is ascribable to the ability of S. boulardii CNCM I-745 to improve the transport of butyrate by the enteric mucosa, as documented by the reduction of faecal butyrate levels and the increased expression of MCT1 transporter.