Treatment of murine colitis by Saccharomyces boulardii secreting atrial natriuretic peptide.

Inflammatory bowel disease is a lifelong disorder that involves chronic inflammation in the small and large intestines. Current therapies, including aminosalicylates, corticosteroids, and anti-inflammatory biologics, can only alleviate the symptoms and often cause adverse effects with long-term usage. Engineered probiotics provide an alternative approach to treat inflammatory bowel disease in a self-renewable and local delivery fashion. In this work, we utilized a yeast probiotic Saccharomyces boulardii for this purpose. We developed a robust method to integrate recombinant genes into the Ty elements of S. boulardii. Stable yeast cell lines that secreted various anti-inflammatory proteins, including IL-10, TNFR1-ECD, alkaline phosphatase, and atrial natriuretic peptide (ANP), were successfully created and investigated for their efficacies to the DSS-induced colitis in mice through oral administration. While IL-10, TNFR1-ECD, and alkaline phosphatase did not show therapeutic effects, the ANP-secreting S. boulardii effectively ameliorated the mouse conditions as reflected by the improvements in body weight, disease activity index, and survival rate. A post-mortem examination revealed that the ANP-treated mice exhibited significant downregulations of TNF-α and IL-1ß and an upregulation of IL-6 in colon tissues. This observation is consistent with the previous reports showing that TNF-α and IL-1ß are responsible for initiating the pathogenesis, whereas IL-6 plays a protective role in colitis. Overall, we demonstrated that S. boulardii is a safe and robust vehicle for recombinant protein delivery in the gastrointestinal tract, and ANP is a potential anti-inflammatory drug for colitis treatment. KEY MESSAGES: Recombinant genes can be robustly integrated into the transposable elements of S. boulardii. Oral administration of S. boulardii secreting IL-10 or TNF-α inhibitor did not exert therapeutic effects for DSS-induced colitis in mice. Atrial natriuretic peptide-secreting S. boulardii effectively ameliorated the murine colitis as reflected by improved body weight, disease activity index, and survival rate. The ANP-treated mice exhibited decreased mRNA levels of TNF-α and IL-1ß and an increased mRNA level of IL-6 in colon tissues.

Saccharomyces boulardii CNCM I-745 probiotic does not alter the pharmacokinetics of amoxicillin.

Background Probiotics are live microbial organisms that provide benefit to the host while co-habitating in the gastrointestinal tract. Probiotics are safe, available over the counter, and have clinical benefit by reducing the number of antibiotic-associated diarrhea days. Prescriptions from providers and direct consumer demand of probiotics appear to be on the rise. Several recent animal studies have demonstrated that probiotics may have significant effect on absorption of co-administered drugs. However, to date, most probiotic-drug interaction studies in animal models have been limited to bacterial probiotics and nonantibiotic drugs. Methods We performed a traditional pharmacokinetic mouse study examining the interactions between a common commercially available yeast probiotic, Saccharomyces boulardii CNCM I-745 (Florastor®) and an orally administered amoxicillin. Results We showed that there were no significant differences in pharmacokinetic parameters (half-life, area under the curve, peak concentrations, time to reach maximum concentration, elimination rate constant) of amoxicillin between the probiotic treated and untreated control groups. Conclusions Altogether, our findings suggest that coadministration or concurrent use of S. boulardii probiotic and amoxicillin would not likely alter the efficacy of amoxicillin therapy.

Growth performance, nutrient digestibility, bone mineralization, and hormone profile in broilers fed with phosphorus-deficient diets supplemented with butyric acid and Saccharomyces boulardii.

The present study evaluated the effects of butyric acid supplementation and Saccharomyces boulardii (alone or in combination) on growth performance, nutrient digestibility, bone mineralization, and blood hormones of male broiler chickens fed a diet including reduced levels of nonphytate phosphorus (NPP). The chickens were allocated to 6 dietary treatments: 1) positive control diet with adequate amounts of NPP (PC; 0.48, 0.43, and 0.39% in the starter, grower, and finisher period, respectively); 2) negative control diet with low amounts of NPP (NC; 0.38, 0.33, and 0.29% in the starter, grower, and finisher period, respectively); 3) NC plus 500 FTU/kg microbial phytase (PHY); 4) NC plus 0.2% butyric acid (BA); 5) NC plus 1 × 108 cfu/kg S. boulardii (SB); 6) NC plus butyric acid and S. boulardii (BA+SB). Each treatment had 5 pen replicates of 25 birds. After 6 wk, the body weight and ADG in birds fed with any of the diets were higher (P < 0.001) than those in birds fed with the NC diet, where the birds fed with the PHY and BA+SB diets had the highest values. However, only the PHY diet improved (P = 0.041) overall F:G. All diets, except the SB diet, resulted in the increased apparent ileal digestibility coefficient (AIDC) of CP, AMEn, and tibia ash content and decreased serum alkaline phosphatase level compared with the NC diet (P < 0.05). Broiler chickens fed with the PHY, SB, and BA+SB diets also had increased AIDC of phosphorus (P = 0.017) than those fed with the NC and PC diets. Feeding PC, PHY, and BA+SB diets increased (P = 0.007) the tibia phosphorus content but decreased (P = 0.033) serum parathyroid hormone concentration. Overall, the present data indicate that the simultaneous inclusion of butyric acid plus S. boulardii in the low-NPP diets was beneficial for improving growth rate and bone mineralization, but not for feed efficiency.