# \(\beta\)-Glucans from Yeast--Immunomodulators from Novel Waste Resources
## 6 Yeast \(\beta\)-Glucan Administration to Humans
### Immune-Modulatory Effects of Black Yeast \(\beta\)-Glucan  
_Aureobasidium pullulans_ produce a \(\beta\)-glucan extracellularly. A study by [PERSON] et al. (2013), analysed the effects of \(\beta\)-glucans isolated from _A. pullulans_ on intestinal immune systems in normal and immunosuppressed mice. After treatment, cells from the Peyer's patch (P.P.) secrete higher IL-5, IL-6, and IgA levels. Dendritic cells from the Peyer's patch secreted more elevated levels of IL-6 when treated with the \(\beta\)-glucans. After oral administration, IgA production was higher in the intestine. This work demonstrated that \(\beta\)-glucans have the potential to activate dendritic cells in the Peyer's patches and induce IL-6 and IgA from the Peyer cells [83].  
[PERSON] et al. (2021), investigated a low molecular weight \(\beta\)-glucans isolated from _A. pullulans_ and their anti-inflammatory ability by measuring reducing LPS-activated Nuclear factor-kappa B (NF-kB) and mitogen-activated protein kinase pathway (MAPKs) in LPS-stimulated RAW 264.7 cells. \(\beta\)-glucans isolated from _A. pullulans_, despite numerous potential benefits, have not translated to clinical application. A reason for this is the high viscosity of the extracellular polysaccharide; therefore, in this study, the authors reduced the thickness and molecular weight using mechanochemical ball-milling and named the extract LMW-AP-FBG. Results demonstrated that LMW-AP-FBG reduced LPS-induced nitric oxide, IL-1\(\beta\), TNF-\(\alpha\), and IL-6 secretion, with more significant effects observed in the higher doses used. The extract also decreased LPS-induced inflammation by inhibiting NF-kB and MAPK signalling pathways. Other studies using \(\beta\)-glucans _A. pullulans_ found that the extract induced the production of IL-5, IL-6, and IgA in the Peyer's patches [1].  
The pathophysiology of COVID-19 is characterised by the presence of endothelial dysfunction that characterises pulmonary injury in both epithelial and endothelial cells of the alveolar-capillary barrier [84].  
The immunological profile of COVID-19 from pathogenesis through progression to severe illness has been described as distinct, with a cytokine storm measured by elevation of biomarkers such as IL-6 assessed by elevation of markers such as D-Dimer. In this pilot clinical study, the authors describe the positive benefits of \(\beta\)-glucans generated from two strains of _A. pullulans_ on biomarkers for cytokine storm in COVID-19 patients. In either of the groups, there was no mortality or need for ventilation of the participants. The combination of \(\beta\)-glucans was effective in lowering D-Dimer levels; they were maintained on day 30. Levels rose in the control group. In COVID-19, IL-6 levels were considerably high and related to poor clinical outcomes. In the current study, IL-6 levels were reduced from levels that predicted more significant mortality due to COVID-19. On day 30, it returned to normal levels in the \(\beta\)-glucans groups exclusively, but it climbed to levels predictive of more significant mortality in the control groups. The addition of \(\beta\)-glucans has aided in preserving the primary biomarkers of clinical severity and mortality of COVID-19 [85]. This study is an excellent prediction of the potential benefits of clinical administration of \(\beta\)-glucans. As this was pilot research with few participants, validation in more extensive multi-centric clinical studies would be required [85].