Dietary ß-glucan (MacroGard®) improves innate immune responses and disease resistance in Nile tilapia regardless of the administration period.

The effects of dietary ß-glucan on innate immune responses have been shown in a number of different vertebrate species. However, there is conflicting information about the period of administration (shorter vs. longer), and it is also unclear to what extent ß-glucan's effects can be observed post-treatment in fish. Thus, we fed Nile tilapia for 0 (control group; 45 days of control diet), 15 (30 days of control followed by 15 days of ß-glucan), 30 (15 days of control followed by 30 days of ß-glucan) or 45 days with a diet containing 0.1% of ß-glucan (MacroGard®). We evaluated the growth performance at the end of the ß-glucan feeding trial and the innate immune function immediately after the feeding trial and 7 and 14 days post-feeding trial. In addition, at day 10 post-feeding trial, we assessed the tilapia's resistance against a bacterial infection. No significant differences were observed in growth performance between the groups; however, fish fed with ß-glucan for 30 and 45 days had higher (approx. 8%) relative weight gain compared to the control. Regardless of the administration period, fish fed with ß-glucan had higher innate immune responses immediately after the feeding trial such as lysozyme activity in plasma, liver and intestine and respiratory burst compared to the control, and in general these differences were gradually reduced over the withdrawal period (up to 14 days). No differences were observed in the plasma hemolytic activity of the complement or myeloperoxidase activity in plasma or intestine. Moreover, fish from the control group had early mortalities (2 vs. 4-5 days post-infection, respectively) and a lower survival rate (60 vs. 80%, respectively) compared to fish fed with ß-glucan for 15 or 30 days, and, interestingly, fish fed for 45 days with ß-glucan had no mortality. This study indicates that regardless of the administration period (i.e., 15 up to 45 days), the ß-glucan improved the innate immune responses and the tilapia's resistance to disease, and this protection could be observed up to 10 days post-feeding trial, adding in vivo evidence that ß-glucan may contribute to a trained innate immunity. Additionally, we showed that a longer period of administration did not cause immunosuppression as previously hypothesized but promoted further growth and immune performance. These findings are relevant to the aquaculture industry and demonstrate that a longer ß-glucan feeding protocol may be considered to achieve better results.

Selenization of S. cerevisiae increases its protective potential in experimental autoimmune encephalomyelitis by triggering an intestinal immunomodulatory loop.

Multiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.

Organic Selenium Reaches the Central Nervous System and Downmodulates Local Inflammation: A Complementary Therapy for Multiple Sclerosis?

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). The persistent inflammation is being mainly attributed to local oxidative stress and inflammasome activation implicated in the ensuing demyelination and axonal damage. Since new control measures remain necessary, we evaluated the preventive and therapeutic potential of a beta-selenium-lactic acid derivative (LAD-ßSe), which is a source of organic selenium under development, to control experimental autoimmune encephalomyelitis (EAE) that is an animal model for MS. Two EAE murine models: C57BL/6 and SJL/J immunized with myelin oligodendrocyte glycoprotein and proteolipid protein, respectively, and a model of neurodegeneration induced by LPS in male C57BL/6 mice were used. The preventive potential of LAD-ßSe was initially tested in C57BL/6 mice, the chronic MS model, by three different protocols that were started 14 days before or 1 or 7 days after EAE induction and were extended until the acute disease phase. These three procedures were denominated preventive therapy -14 days, 1 day, and 7 days, respectively. LAD-ßSe administration significantly controlled clinical EAE development without triggering overt hepatic and renal dysfunction. In addition of a tolerogenic profile in dendritic cells from the mesenteric lymph nodes, LAD-ßSe also downregulated cell amount, activation status of macrophages and microglia, NLRP3 (NOD-like receptors) inflammasome activation and other pro-inflammatory parameters in the CNS. The high Se levels found in the CNS suggested that the product crossed the blood-brain barrier having a possible local effect. The hypothesis that LAD-ßSe was acting locally was then confirmed by using the LPS-induced neurodegeneration model that also displayed Se accumulation and downmodulation of pro-inflammatory parameters in the CNS. Remarkably, therapy with LAD-ßSe soon after the first remitting episode in SJL/J mice, also significantly downmodulated local inflammation and clinical disease severity. This study indicates that LAD-ßSe, and possibly other derivatives containing Se, are able to reach the CNS and have the potential to be used as preventive and therapeutic measures in distinct clinical forms of MS.

Effects of the solubility of yeast cell wall preparations on their potential prebiotic properties in dogs.

Derivatives of yeast cell wall (YCW) have been studied for their potential prebiotic effects. Recently, new purified and soluble preparations have been developed in an attempt to increase their biological actions. Two YCW preparations, one conventional and another with higher solubility of the mannan oligosaccharide fraction, were evaluated on dogs. One food formulation was used, divided into the following treatments: CON-control, without yeast cell wall addition; YCW-addition of 0.3% of a conventional yeas cell wall extract; YCWs-addition of 0.3% of a yeast cell wall extract with high mannan oligosaccharide solubility. Twenty-four beagle dogs were used, eight per food, distributed on a block design. Blocks lasted 32 days, and TNF-a, IL-6, IL-10, ex vivo production of hydrogen peroxide and nitric oxide by peripheral neutrophils and monocytes, phagocytic index, and fecal IgA were evaluated at the beginning and end of each period. Additionally, nutrient digestibility, feces production and quality, and fermentation products were quantified. The results were evaluated by analysis of variance and compared using the Tukey test (P<0.05), using the basal immunological parameters as a covariate. The inclusion of YCWs reduced fat digestibility (P<0.05), increased the concentration of butyrate and putrescine, and reduced lactate in feces (P<0.05), showing that mannan oligosaccharide solubilization resulted in higher fermentation of this compound and altered the metabolism of the gut microbiota. Lower IL-6 on serum was verified for dogs fed the YCWs diet (P<0.05), suggesting a reduction in the inflammatory activity of dogs. Higher phagocytic index was verified for peripheral monocytes after the intake of the YCW food, suggesting better innate immunity. In conclusion, the solubilization of the mannooligosaccharide fraction alters its interaction with gut microbiota and biological actions in animals, although both yeast cell wall preparations exhibited prebiotic effects on dogs.