Beneficial effects of 1,3-1,6 ß-glucans produced by Aureobasidium pullulans on non-esterified fatty acid levels in diabetic KKAy mice and their potential implications in metabolic dysregulation.

Objectives: In this study, we used an obese and diabetic mouse model to compare two strains of Aureobasidium pullulans (AFO-202 and N-163) produced beta-glucans (ß-glucans), which alleviate lipotoxicity. Methods: Four groups of KK-Ay mice were used, with six subjects in each group. Group 1: sacrificed on day 0 for baseline values; Group 2: control (drinking water); Group 3: AFO-202 beta glucan-200 mg/kg/day; Group 4: N-163 beta glucan-300 mg/kg/day for 28 consecutive days. Results: Group 4 (N-163) had the lowest non-esterified fatty acids (NEFA) levels and marginally decreased triglyceride levels compared to the other groups. There were no significant differences in blood glucose, hemoglobin A1c (HbA1c), triglycerides, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol levels. N-163 ß-glucans decreased NEFA levels after 28 days. Conclusion: These results, although modest, warrant further in-depth research into lipotoxicity and associated inflammatory cascades in both healthy and diseased subjects for the prevention and management of metabolic dysregulation and associated diseases such as non-alcoholic fatty liver disease (NAFLD).

Hepatoprotective Effects of Aureobasidium pullulans Derived ß 1,3-1,6 Glucans in a Murine Model of Non-alcoholic Steatohepatitis.

Background: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Conventional modalities are mainly symptomatic, with no definite solution. Beta-glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta-glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study. Methods: In the STAM™ murine model of NASH, five groups were studied for 8 weeks: (1) vehicle (RO water), (2) AFO-202 beta-glucan; (3) N-163 beta-glucan, (4) AFO-202+N-163 beta-glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed. Results: AFO-202 beta-glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta-glucan decreased fibrosis and inflammation significantly (P value < 0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups. Conclusion: This preclinical study supports the potential of N-163 and AFO-202 beta-glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.

ß­glucan vaccine adjuvant approach for cancer treatment through immune enhancement (B­VACCIEN) in specific immunocompromised populations (Review).

The incidence of cancer, which is the second leading cause of mortality globally, continues to increase, although continued efforts are being made to identify effective treatments with fewer side­effects. Previous studies have reported that chronic microinflammation, which occurs in diseases, including diabetes, along with weakened immune systems, may ultimately lead to cancer development. Chemotherapy, radiotherapy and surgery are the mainstream approaches to treatment; however, they all lead to immune system weakness, which in turn increases the metastatic spread. The aim of the present review was to provide evidence of a biological response modifier ß­glucan [ß­glucan vaccine adjuvant approach to treating cancer via immune enhancement (B­VACCIEN)] and its beneficial effects, including vaccine­adjuvant potential, balancing metabolic parameters (including blood glucose and lipid levels), increasing peripheral blood cell cytotoxicity against cancer and alleviating chemotherapy side effects in animal models. This suggests its value as a potential strategy to provide long­term prophylaxis in immunocompromised individuals or genetically prone to cancer.

Beneficial Effects of novel Aureobasidium Pullulans strains produced Beta-1,3-1,6 Glucans on Interleukin-6 and D-Dimer levels in COVID-19 patients; results of a randomized multiple-arm pilot clinical study

ObjectiveCytokine storm and Coagulopathy have been implicated as major causes of morbidity and mortality in COVID-19 patients. A black yeast Aureobasidium pullulans AFO-202 strain produced beta 1,3-1,6 glucan has been reported to offer potential immune enhancement and metabolism balancing, as well as mitigation of coagulopathy risks. The N-163 strain produced beta glucan is an efficient anti-inflammatory immune modulator. In this pilot clinical study, we report the beneficial effects of these two beta glucans on the biomarkers for cytokine storm and coagulopathy in COVID-19 patients. MethodsA total of 24 RT-PCR positive COVID-19 patients were recruited (Age range: 18[~]62; 17 males and 7 females). Patients were randomly divided into three groups (Gr): Gr. 1 control (n=8); Gr. 2: AFO-202 beta glucan (n=8); and Gr. 3, a combination of AFO-202 and N-163 beta glucans (n=8). All three groups received the standard care while groups 2 and 3 received additional supplementation of beta glucans for 30 days. In addition to basic clinical parameters, we periodically evaluated D-Dimer, IL-6, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the neutrophil to lymphocyte ratio (NLR), the lymphocyte to CRP ratio (LCR) and the leukocyte-CRP ratio (LeCR). ResultsThe duration of hospital stay for all three groups was nearly equivalent. There was no mortality of the subjects in any of the groups. Intermittent oxygen was administered from day of admission for up to four to five days with mask (two to four Lpm) to two subjects in Gr. 2 and one subject in Gr. 3. None of the subjects required ventilation. The D-Dimer values in Gr. 1, which was on average 751 ng/ml at baseline, decreased to 143.89 ng/ml on day 15, but increased to 202.5 ng/ml on day 30, which in groups 2 and 3 decreased on day 15 and continued to remain at normal levels until day 30. IL-6 levels decreased on day 15 from an average of 7.395 pg/ml to 3.16 pg/ml in the control, 26.18 pg/ml to 6.94 pg/ml in Gr. 2 and 6.25 pg/ml to 5.22 pg/ml in Gr. 3. However, when measured on day 30, in Gr. 1, the IL-6 increased to 55.37 pg/ml while there was only slight marginal increase in Gr. 2 but within normal range, and the levels further decreased to less than 0.5 pg/ml in Gr. 3. The same trend was observed with ESR. LCR and LeCR increased significantly in Gr. 3. NLR decreased significantly in groups 2 and 3. There was no difference in CRP within the groups. ConclusionIn this exploratory study, consumption of Aureobasidium pullulans produced beta glucans for thirty days, results in a significant control of IL6, D-Dimer and NLR, a significant increase in LCR, LeCR and marginal control of ESR in COVID-19 patients. As these beta glucans are well known food supplements with decades of a track record for safety, based on these results, we recommend larger multi-centric clinical studies to validate their use as an adjunct in the management of COVID-19 and the ensuing long COVID-19 syndrome.