Probiotic survival during a multi-layered tablet development as tested in a dynamic, computer-controlled in vitro model of the stomach and small intestine (TIM-1).

The aim of the research was to develop a galenical formulation for the combination of the three probiotic strains Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3 and Bifidobacterium bifidum MF 20/5 that would lead to the presence of a high amount of viable cells in the small intestine, the presumed site of action of these strains. This was tested in a validated, dynamic in vitro model of the stomach and small intestine (TIM-1), simulating human adults after intake of a meal. Experiments were performed both in the gastric compartment of the model, as well as in the complete system (stomach + small intestine). Survival of the strains in an unformulated probiotic powder after transit through the gastric compartment was 5·3% for the bifidobacteria and 1% for L. gasseri. After transit through the complete gastrointestinal tract, this dropped to 2% for bifidobacteria and 0·1% for Lactobacillus. After several rounds of optimization, an enteric-coated tablet was developed that increased the delivery of viable cells reaching the small intestine to 72% (gastric survival) for bifidobacteria, and 53% (gastric) for L. gasseri. Also survival in the small intestine increased by about an order of magnitude. The final galenical formulation was tested in two applications: adults and elderly, both of which have their own physiological parameters. These experiments corroborated the results obtained in the development phase of the project. In conclusion, the developed enteric coating led to a 20- to 40-fold increase in the delivery of viable cells to the small intestine. SIGNIFICANCE AND IMPACT OF THE STUDY: Predictive GI in vitro models are very helpful and reliable tools for the development of new galenical formula containing probiotics, and in the current example helped to deliver >10-fold higher numbers of viable cells to the small intestine, presumably leading to improved functionality of the strains.

Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN Study).

BACKGROUND/OBJECTIVES: An imbalance between Th1 and Th2 cells is involved in allergic rhinitis (AR) that may be improved by probiotics. To test the efficacy of the probiotic Lactobacillus paracasei subsp. paracasei LP-33, a double-blind, placebo-controlled, randomized trial was carried out in patients with AR to grass pollen treated with loratadine and presenting altered quality of life. SUBJECTS/METHODS: Subjects with persistent AR, symptomatic during the grass pollen season, and a positive skin test or specific immunoglobulin E to grass pollens were included by general practitioners (GPs). All received loratadine for 5 weeks. The primary end point was the improvement in Rhinitis Quality of Life (RQLQ) global score at the fifth week of LP-33 consumption compared with placebo (in addition to loratadine). Secondary end points included nasal and ocular symptoms (individual and total symptom scores), visual analogue scale and time of first exacerbation of the symptoms when loratadine was stopped. RESULTS: A total of 425 subjects were included. Using intent-to-treat analysis, the RQLQ global score decreased significantly more in the LP-33 group than in the placebo group (P=0.0255, difference=-0.286 (95% confidence interval (CI): -0.536; -0.035)). No significant differences were noted for the change of the rhinitis total symptom score 5 global score between groups (P=0.1288, difference=-0.452 (95% CI: -1.036; 0.132)). Significant differences in ocular symptoms (RQLQ) were observed between groups (P=0.0029, difference=-0.4087 (95% CI: -0.6768; -0.1407)). CONCLUSIONS: This study performed by GPs shows that LP-33 improves the quality of life of subjects with persistent AR who are currently being treated with an oral H1-antihistamine. Whereas nasal symptoms had not changed, ocular symptoms had consistently improved.

Beneficial effects of probiotics in upper respiratory tract infections and their mechanical actions to antagonize pathogens.

Probiotics are live micro-organisms with beneficial effects on human health, which have the ability to counteract infections at different locations of the body. Clinical trials have shown that probiotics can be used as preventive and therapeutic agents in upper respiratory tract infections (URTIs) and otitis. Their mechanical properties allow them to aggregate and to compete with pathogens for nutrients, space and attachment to host cells. Consequently, they can directly antagonize pathogens and thus exert beneficial effects without directly affecting the metabolism of the host. An overview of the probiotics with such traits, tested up to date in clinical trials for the prevention or treatment of URTIs and otitis, is presented in this review. Their mechanical properties in the respiratory tract as well as at other locations are also cited. Species with interesting in vitro properties towards pharyngeal cells or against common respiratory pathogens have also been included. The potential safety risks of the cited species are then discussed. This review could be of help in the screening of probiotic strains with specific mechanical properties susceptible to have positive effects in clinical trials against URTIs.