In Vitro Functional and Immunomodulatory Properties of the Lactobacillus helveticus MIMLh5-Streptococcus salivarius ST3 Association That Are Relevant to the Development of a Pharyngeal Probiotic Product

Department of Food Science and Microbiology, Università degli Studi di Milano, Milan, Italy.
Applied and Environmental Microbiology (Impact Factor: 3.67). 04/2012; 78(12):4209-16. DOI: 10.1128/AEM.00325-12
Source: PubMed


The use of proper bacterial strains as probiotics for the pharyngeal mucosa is a potential prophylactic strategy for upper respiratory tract infections. In this context, we characterized in vitro the functional and immunomodulatory properties of the strains Lactobacillus helveticus MIMLh5 and Streptococcus salivarius ST3 that were selected during previous investigations as promising pharyngeal probiotics. In this study, we demonstrated in vitro that strains MIMLh5 and ST3, alone and in combination, can efficiently adhere to pharyngeal epithelial cells, antagonize Streptococcus pyogenes, and modulate host innate immunity by inducing potentially protective effects. In particular, we found that the strains MIMLh5 and ST3 activate U937 human macrophages by significantly inducing the expression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α). Nonetheless, the induction of the anti-inflammatory interleukin-10 (IL-10) by MIMLh5 or ST3 was never lower than that of TNF-α, suggesting that these bacteria can potentially exert a regulatory rather than a proinflammatory effect. We also found that the strains MIMLh5 and ST3 induce cyclooxygenase 2 (COX-2) expression and demonstrated that toll-like receptor 2 (TLR-2) participates in the recognition of the strains MIMLh5 and ST3 by U937 cells. Finally, we observed that these microorganisms grow efficiently when cocultured in milk, suggesting that the preparation of a milk-based fermented product containing both MIMLh5 and ST3 can be a practical solution for the administration of these bacteria. In conclusion, we propose the combined use of L. helveticus MIMLh5 and S. salivarius ST3 for the preparation of novel products that display probiotic properties for the pharyngeal mucosa.

Download full-text


Available from: Matti Karp,
53 Reads
  • Source
    • "So far, lactobacilli have been predominantly investigated and explicitly proposed as probiotics for their potential beneficial roles on the gastrointestinal tract and its microbiota (Guglielmetti et al., 2011; Ferrario et al., 2014). Nevertheless, the interest for the application of lactobacilli beyond the gut is constantly increasing, leading to the development of new categories of probiotic products that target oral cavity (Guglielmetti et al., 2010a,b; Taverniti et al., 2012; Wescombe et al., 2012), skin (Krutmann, 2009), stomach (Johnson-Henry et al., 2004), urinary tract (Borchert et al., 2008), and vaginal mucosa (Borges et al., 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial vaginosis is one of the most common urogenital diseases affecting women in reproductive age. The administration of probiotics as vaginal suppository has been proposed as a strategy to cure this condition and reduce its recurrence. Nonetheless, also oral consumption of probiotics, which is a more practical route of administration, proved to be an efficient strategy. In this perspective, we studied Lactobacillus paracasei LPC-S01 (DSM 26760), a human vaginal isolate included in commercial probiotic preparations for topical use, in order to assess if this bacterium can also perform as gastrointestinal probiotic. Comparative genomics revealed the presence of several accessory genes suggesting that LPC-S01 is a niche-generalist member of its species. According to a procedure conventionally used to predict the probiotic potential, we demonstrated that the probiotic properties of strain LPC-S01, with respect to those of the well-known probiotic references L. paracasei Shirota and DG, are equal for the bile tolerance and the reduction of NF-κB activation in Caco-2 cells, or superior for the tolerance to gastric juice and the adhesion to Caco-2 epithelial cells. We then demonstrated that LPC-S01 is susceptible to antibiotics indicated by EFSA and does not produce biogenic amines. Finally, a double-blind cross-over pilot intervention trial on healthy human volunteers showed that, after a 7-days oral consumption of capsules containing about 24 billion live cells, the fecal cell concentrations of strains LPC-S01 and DG (evaluated by qPCR) were not dissimilar. Specifically, both probiotics' cell concentrations were above the detection limit for an average of 5 days from the end of the treatment, corresponding to a mean number of evacuations of 7 ± 2. Taken together, these data demonstrate that the vaginal isolate L. paracasei LPC-S01 possesses safety and functional properties that may support its use as probiotic to be administered per os for potential intestinal as well as vaginal applications.
    Frontiers in Microbiology 09/2015; 6. DOI:10.3389/fmicb.2015.00952 · 3.99 Impact Factor
  • Source
    • "Activated DCs, together with the production of IL-2 (Granucci et al., 2003), are necessary to prime natural killer (NK) cells to produce IFNγ and to induce a Th1 response. In a subsequent study, strain MIMLh5 was tested together with the oral isolate S. salivarius ST3 (Guglielmetti et al., 2010a) on the human macrophage U937 cell line (Taverniti et al., 2012). The combination of MIMLh5 and ST3 elicited a balanced ratio of TNF-α and IL-10 that might be produced by a mild activation of the immune system and may be useful for combating infections, potentially without causing a detrimental outcome. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Lactobacillus helveticus is an important industrial thermophilic starter that is predominantly employed in the fermentation of milk for the manufacture of several cheeses. In addition to its technological importance, a growing body of scientific evidence shows that strains belonging to the L. helveticus species have health-promoting properties. In this review, we synthesize the results of numerous primary literature papers concerning the ability of L. helveticus strains to positively influence human health. Several in vitro studies showed that L. helveticus possesses many common probiotic properties, such as the ability to survive gastrointestinal transit, adhere to epithelial cells, and antagonize pathogens. In vivo studies in murine models showed that L. helveticus could prevent gastrointestinal infections, enhance protection against pathogens, modulate host immune responses, and affect the composition of the intestinal microbiota. Interventional studies and clinical trials have also demonstrated a number of health-promoting properties of L. helveticus. Finally, several studies suggested that specific enzymatic activities of L. helveticus could indirectly benefit the human host by enhancing the bioavailability of nutrients, removing allergens and other undesired molecules from food, and producing bioactive peptides through the digestion of food proteins. In conclusion, this review demonstrates that in light of the scientific literature presented, L. helveticus can be included among the bacterial species that are generally considered to be probiotic.
    Frontiers in Microbiology 11/2012; 3:392. DOI:10.3389/fmicb.2012.00392 · 3.99 Impact Factor
  • Source
    • "helveticus MIMLh5, strain ST3 adheres to pharyngeal epithelial cells, antagonizes Strep. pyogenes and modulates host innate immunity by inducing potentially protective effects (Taverniti et al. 2012). Strain NCC1561 modulates the growth of oral bacteria in vitro (Comelli et al. 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of Applied Microbiology 07/2012; 113(6). DOI:10.1111/j.1365-2672.2012.05394.x · 2.48 Impact Factor
Show more