RESUMEN
The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.
RESUMEN
Background: The administration of probiotics has been shown to be beneficial in asthma. The administration of Saccharomyces cerevisiae UFMG A-905 prevented asthma development. Traditionally, probiotics are administered using dairy-based matrices, but other vehicles (e.g., fruit juices, biscuits, candies, and breads) can be used. Objectives: This study aimed to assess the effect of bread fermented with S. cerevisiae UFMG A-905 in asthma prevention. Methods: Three breads were produced: fermented with commercial yeast, fermented with S. cerevisiae UFMG A-905, and fermented with S. cerevisiae UFMG A-905 with the addition of alginate microcapsules containing live S. cerevisiae UFMG A-905. Characterization of the microbial composition of the breads was performed. Male Balb/c mice were sensitized and challenged with ovalbumin. Breads were administered 10 d before the first sensitization and during sensitization and challenge protocol. Yeast fecal count, in vivo airway hyperresponsiveness, and airway and lung inflammation were assessed. Results: In UFMG A-905 bread, there was an increase in yeast number and a decrease in total and lactic acid bacteria. Animals that received S. cerevisiae UFMG A-905 fermented bread with microcapsules had a significant increase in yeast recovery from feces. S. cerevisiae UFMG A-905-fermented breads partially reduced airway inflammation, decreasing eosinophils and IL5 and IL13 concentrations. When adding microcapsules, the bread also diminished airway hyperresponsiveness and increased IL17A concentrations. Conclusions: S. cerevisiae UFMG A-905 was able to generate long-fermentation breads. Microcapsules were a safe and viable way to inoculate the live yeast into food. The administration of breads fermented with S. cerevisiae UFMG A-905 prevented asthma-like characteristics, being more pronounced when the breads contained microcapsules with live yeast.
RESUMEN
Probiotics should be administered in adequate amounts to confer health benefits. Probiotic dose-response studies are still missing. Saccharomyces cerevisiae UFMG A-905 prevented asthma development; however, the ideal dose has not been investigated. We evaluated the optimal dose and administration regimen of S. cerevisiae UFMG A-905 in the prevention of asthma. Male Balb/c mice were sensitized intraperitoneally with ovalbumin (OVA) and challenged with OVA intranasally. Mice received, via gavage, daily or alternate-day S. cerevisiae UFMG A-905. In daily regimen, different concentrations (107, 108, or 109 CFU/mL) were given 10 days before OVA sensitization and during challenges. In alternate-day regimen, a concentration of 109 CFU/mL was administered three times per week for 5 weeks, starting 2 weeks prior to the first sensitization. After the last challenge, in vivo bronchial hyperresponsiveness and airway and lung inflammation were assessed. OVA-challenged mice, when compared to saline-challenged mice, presented a significant increase in bronchial hyperresponsiveness and airway and lung inflammation. Daily and alternate-day administration of 109 CFU/mL of S. cerevisiae UFMG A-905 significantly reduced bronchial hyperresponsiveness; lower concentrations of S. cerevisiae UFMG A-905 did not significantly reduce bronchial hyperresponsiveness. Daily regimen with the highest concentration significantly reduced total cell number, eosinophil count in the BAL, and the levels of IL-4, IL-5, and IL-13. Daily administration of S. cerevisiae UFMG A-905 at 107 and 108 CFU/mL and alternate-day regimen did not significantly decrease airway and lung inflammation. S. cerevisiae UFMG A-905 led to a significant attenuation of bronchial hyperresponsiveness and lung inflammation in a dose-dependent manner.