Saccharomyces cerevisiae UFMG A-905 acts in an animal model of asthma by modulating Th17/Treg responses and increasing fatty acid production

Abstract

Background: Asthma prevalence has been increasing, particularly among children and in populations transitioning to Western lifestyle. According to the hygiene hypothesis, early-life exposure to microorganisms may protect against asthma and other allergic conditions. Previous studies demonstrated that Saccharomyces cerevisiae UFMG A-905 reduce bronchial hyperresponsiveness, airway and lung inflammation, and restore IL-10 and IFN-γ. However, the underlying mechanisms remain unclear.

Objective: To investigate the potential pathways by which S. cerevisiae UFMG A-905 modulates asthma.

Materials and methods: Wild-type and Il17a⁻/⁻ mice were treated daily with live yeast or its supernatant (postbiotic) by oral gavage, starting ten days before OVA sensitization and maintained during sensitization and challenge. Control groups received saline. Lung tissues were analyzed by flow cytometry to assess dendritic cells and regulatory T cells. Gene expression of TLR-9, NLRP3, Dectin-1, and Mincle was quantified by qPCR. Short-, medium-, and long-chain fatty acids were measured in feces using gas chromatography, while gut cytokine were evaluated by ELISA.

Results: Treatment with S. cerevisiae UFMG A-905 led to an increase in CD11c⁺MHCII⁺CD11b⁺CD103⁻ dendritic cells, regulatory T cells (CD4⁺CD25⁺FOXP3⁺), and NLRP3 gene expression in the lung, and the fecal levels of dihomo-γ-linolenic acid. Neither gut cytokines nor OVA specific IgE were affected, and the supernatant did not significantly alter cell counts. The beneficial effects were partially dependent on IL-17A.

Conclusion: The effects observed with S. cerevisiae UFMG A-905 correlated with modulation of Th17, dendritic-cell and regulatory T-cell responses, upregulation of NLRP3, and increased fatty acid production, suggesting gut-lung axis involvement.

Keywords: S. cerevisiae UFMG A-905; Asthma; Prevention; Probiotics.

Fig. 1

Saccharomyces cerevisiae UFMG A-905 administration increases the number of CD11c⁺MHCII⁺CD11b⁺CD103⁻ dendritic cells and the percentage of regulatory T cells in lung tissue. Dendritic and regulatory cells were analyzed by flow cytometer. (A-B) Gating strategy used to identify dendritic cells. (C-D) Quantitative analysis of dendritic cells. (E-F) Gating strategy used to identify regulatory T cells. (G) Quantitative analysis of regulatory T cells. Values are shown as box-and-whisker plots (n = 8). *p < 0.05; **p < 0.01; SAL/PBS: BALB/c mice sensitized and challenged with saline, received PBS; OVA/PBS: BALB/c mice sensitized and challenged with ovalbumin (OVA), received PBS; OVA/Sac: BALB/c mice sensitized and challenged with OVA, received S. cerevisiae UFMG A-905

Fig. 2

Effect of Saccharomyces cerevisiae UFMG A-905 on TLR-9 (A), NLRP3 (B), Dectin-1 (C), and Mincle (D) expression in lung tissue. Gene expression was performed by real-time-PCR. Values are shown as box-and-whisker plots (n = 7) * p < 0.05; SAL/PBS: BALB/c mice sensitized and challenged with saline, received PBS; OVA/PBS: BALB/c mice sensitized and challenged with ovalbumin (OVA), received PBS; OVA/Sac: BALB/c mice sensitized and challenged with OVA, received S. cerevisiae UFMG A-905

Fig. 3

Saccharomyces cerevisiae UFMG A-905 increased the fecal percentage of dihomo-γ-linolenic acid and decreased the percentage of dodecanoic acid and oleic acid. Fatty acids were measured in fecal samples using a gas chromatographic method. (A-C) Short-chain fatty acids. (D) Medium-chain fatty acid. (E-I) Long-chain fatty acids. Values are shown as box-and-whisker plots (n = 8). * p < 0.05; **p < 0.001; SAL/PBS: BALB/c mice sensitized and challenged with saline, received PBS; OVA/PBS: BALB/c mice sensitized and challenged with ovalbumin (OVA), received PBS; OVA/Sac: BALB/c mice sensitized and challenged with OVA, received S. cerevisiae UFMG A-905

Fig. 4

Effects of Saccharomyces cerevisiae UFMG A-905 on airway total and differential cell counts and IL-13 levels in BALB/c wild-type and C57BL/6 Il17a⁻/⁻ mice. (A) Total cell counts. (B-E) Differential cell counts. (F) IL-13 levels. Values are shown as box-and-whisker plots (n = 8). *p < 0.05; **p < 0.01; ***p < 0.001; SAL/PBS: mice sensitized and challenged with saline, received PBS; OVA/PBS: mice sensitized and challenged with ovalbumin (OVA), received PBS; OVA/Sac: mice sensitized and challenged with OVA, received S. cerevisiae UFMG A-905

Fig. 5

Postbiotic derived from Saccharomyces cerevisiae UFMG A-905 did not change the airway cellular response. (A) Total cell counts. (B-E) Differential cell counts. Values are shown as box-and-whisker plots (n = 8). * p < 0.05; **p < 0.01; ****p < 0.0001; SAL/PBS: BALB/c mice sensitized and challenged with saline, received PBS; OVA/PBS: BALB/c mice sensitized and challenged with ovalbumin (OVA), received PBS; OVA/Sac: BALB/c mice sensitized and challenged with OVA, received S. cerevisiae UFMG A-905