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Yeast cells can play a crucial role in immune activation in fish and shellfish predominantly due to the cell wall component β-1,3-glucan, providing protection against bacterial or viral infections. However, the immunostimulatory capacity of dietary yeast cells remains poorly studied in bivalves. To understand the role of yeast cell wall components (mannan, β-glucan and chitin) as immune activators, this study characterized the surface carbohydrate exposure of the wild-type baker's yeast Saccharomyces cerevisiae (WT) and its Δmnn9 mutant, which presents a defective mannan structure, and compared these profiles with that of β-glucan particles, using fluorescein isothiocyanate (FITC)-labeled lectin binding analysis. Then, a first trial evaluated the immunological response in Crassostrea gigas juveniles after being fed for 24 h with an algae-based diet (100A) and its 50% substituted version (based on dry weight) with WT (50A50WT) and Δmnn9 (50A50Y), and the posterior resistance of the juveniles against Vibrio coralliilyticus infection (trial 1). The mRNA expression was measured for β-glucan-binding protein (CgβGBP), Toll-like receptor 4 (CgTLR4), C-type lectin receptor 3 (CgCLec-3), myeloid differentiation factor 88 (CgMyD88), nuclear factor-kappa B (CgNFκB), lysozyme (CgLys), interleukin 17-5 (CgIL17-5), and superoxide dismutase (CgSOD), in oysters, before and 24 h after the bacterial inoculation. A second trial tested the effect of incorporating Δmnn9 into the 100A diet for 24 h at different substitution levels: 0, 5, 10, 25, and 50% (100A, 95A5Y, 90A10Y, 75A25Y, and 50A50Y), followed by the bacterial challenge with V. coralliilyticus (trial 2). Our findings showed that the outer cell wall surface of WT is largely composed of mannan, while Δmnn9 presents high exposure of β-glucan and chitin, exhibiting similar FITC-lectin binding profiles (fluorescence intensity) to β-glucan particles. A significantly higher survival after the bacterial challenge was observed in oysters fed on 50A50Y compared to those fed 50A50WT and 100A in trial 1. This better performance of 50A50Y was supported by significantly higher gene expressions of CgLys, CgSOD, CgMyD88, and CgβGBP compared to 100A, and CgSOD and CgNFκB in relation to those fed on 50A50WT, prior to the bacterial inoculation. Furthermore, improved survival was observed in oysters fed 50A50Y compared to those offered lower Δmnn9 levels and 100A in trial 2. The superior performance of Δmnn9-fed oysters is mostly associated with the elevated presence of unmasked β-glucans on Δmnn9 cell wall surface, facilitating their interactions with oyster hemocytes. Further studies are needed to evaluate administration dose and frequency of Δmnn9 to develop strategies for long-term feeding.

Trained immunity refers to the memory acquired by innate immune cells, leading to cross-protection and non-specific responses to subsequent infection, thereby improving host survival. Trained immunity induction is a combined effect of immune signaling, metabolic changes, and epigenetic modifications. The present study evaluated the induction of markers of the phenomenon of trained immunity in common carp, which is trained using β-glucan. The mammalian target of rapamycin (mtor) and hypoxia-inducible factor (hif1α), the metabolic basis of trained immunity; the histone deacetylase (hdac7), one of the markers of epigenetic modifications, metabolic activity of activated cells and expression profiles of proinflammatory cytokines viz. il6a, tnfαa2, and ifnγ were targeted in the study and analyzed in vivo. Besides in vivo analysis, in vitro analysis of mtorc2, hif1α, hdac7, and ifnγ were analyzed. In vitro analyses were performed on head kidney macrophages isolated and maintained in L-15 media and double trained with β-glucan at 100μg/mL. The culture supernatant was collected at different time intervals and processed for expression studies. Healthy common carp were injected with β-glucan at 20 mg/kg body weight for training followed by a resting phase for 6 days and were restimulated with the same dose. Head kidney was collected from the fish post-induction as well as post-restimulation. The expression profile of mtorc2, hdac7, and hif1α were found elevated post-stimulation of β-glucan. Further, a significantly upregulated expression profile of proinflammatory cytokines (ifnγ, il6a and tnfαa2) was observed. Increased glycolysis in the cells post-β-glucan stimulation was confirmed by the high lactate and LDH production detected in the cell culture supernatant. Overall, the study revealed the expression profile of the trained immunity markers and the increased metabolic activity in cells induced with β-glucan, which further validates that the action of trained immunity is indispensable in fish on encounter with a potential ligand. The study supports the existing reports on trained immunity in teleost fish with evidence at the genomic level. However, further studies are required to understand the responses and actions of trained immune cells during infection in detail.

β-glucans are produced by many organisms and could be used as supplementary feed to enhance immunity and growth in some aquatic animals. This study aimed to compare the effectiveness of β-glucans derived from two marine diatoms (Chaetoceros muelleri and Thalassiosira weissflogii) as growth promoters and immunity enhancers in banana shrimp (Penaeus merguiensis). Shrimp were divided into 3 groups: the control group was fed without β-glucan; the second and the third group were fed with 2 g kg

Yuying Xu,1,* Jintao Huang,2,* Yapei Fan,1 Haiyue Long,1 Minting Liang,1 Qunjie Chen,1 Zhiping Wang,2 Chaoxi Wu,1 Yifei Wang1 1Department of Cell Biology, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chaoxi Wu; Yifei Wang, Email chaoxiw@gmail.com; twang-yf@163.comAim: This study focuses on constructing of an anti-inflammatory drug delivery system by encapsulation of berberine in the β-glucan nanoparticles and evaluates its effect on treating ulcerative colitis.Methods: β-Glucan and the anti-inflammatory drug berberine (BER) are self-assembled into nanoparticles to construct a drug delivery system (GLC/BER). The interaction between the drug and the carrier was characterized by circular dichroism, ultraviolet-visible spectroscopy, and dynamic light scattering. The anti-inflammatory effect of the GLC/BER was evaluated through a lipopolysaccharide (LPS)-induced RAW264.7 macrophage inflammation model and a sodium sulfate (DSS)-induced C57BL/6 mouse ulcerative colitis model.Results: The GLC/BER nanoparticles have a particle size of 80– 120 nm and a high encapsulation efficiency of 37.8± 4.21%. In the LPS-induced RAW264.7 macrophage inflammation model, GLC/BER significantly promoted the uptake of BER by RAW264.7 cells. RT-PCR and ELISA assay showed that it could significantly inhibit the inflammatory factors including IL-1β, IL-6 and COX-2. Furthermore, GLC/BER shows inhibiting effect on the secretion of pro-inflammatory factors such as IL-1β and IL-6, down-regulating the production of nitrite oxide; in animal studies, GLC/BER was found to exert a relieving effect on mice colitis.Conclusion: The study found that GLC/BER has an anti-inflammatory effect in vitro and in vivo, and the GLC carrier improves the potency and bioavailability of BER, providing a new type of nanomedicine for the treatment of colitis.Keywords: β-glucan, chiral, drug carrier, immunoregulation, anti-inflammation

Obesity is associated with other diseases such as diabetes and cancer. Botryosphaeran, a fungal (1→3)(1→6)-β-d-glucan, is described to present antimutagenic, hypoglycemic, hypocholesterolemic, and antitumor activities when administered by gavage over 15 days in rats and mice. Thus, the present study aims to analyze the metabolic effects of Botryosphaeran (12 mg/kg body weight/day) treatment over 30 days in obese Wistar male rats. Obesity was induced in the rats by a high-fat/high-sugar diet for 8 weeks. Control rats received a standard diet. On the 5th week, Botryosphaeran treatment commenced. Groups: control, obese, and obese+Botryosphaeran 30 days. In the 8th week, obesity was characterized. Feed intake, glucose and lipid profiles, glucose tolerance, and insulin sensitivity were analyzed. Obese rats showed accumulation of visceral adipose tissue, reduction of muscle mass, glucose intolerance, insulin resistance, hyperglycemia, and dyslipidemia. Botryosphaeran effectively reduced weight gains and the accumulation of retroperitoneal adipose tissue, corrected the levels of glucose, triglycerides, and very low-density lipoprotein-cholestrol, and improved insulin sensitivity. Treatment for 30 days was effective in maintaining the beneficial effects demonstrated by this β-glucan when administered for 15 days without promoting side effects. Treatment with (1→3)(1→6)-β- d-glucan presented anti-obesogenic and beneficial metabolic effects in Wistar rats; important for the treatment of obesity and its comorbidities.

6 Pág. Centro de Investigación en Sanidad Animal (CISA), Disease prevention by vaccination is, on economic, environmental and ethical grounds the most appropriate method for pathogen control currently available to the aquaculture sector. However, vaccine administration in aquatic animals faces obvious technical problems not encountered in other land animals. Thus, oral vaccines are highly demanded by the aquaculture sector that requests alternatives to the labor-intensive injectable vaccines that require individual handling of fish, provoking stress-related immunosuppression and handling mortalities. Despite this, most previous attempts to obtain effective oral vaccines have failed both in fish and mammals. This could be a consequence of very restricted tolerance mechanisms in the intestine given the fact that this mucosa is at the frontline upon antigen encounter and has to balance the delicate equilibrium between tolerance and immunity in a microbe rich aquatic environment. In this context, the search for an optimal combination of antigen and adjuvant that can trigger an adequate immune response able to circumvent intestinal tolerance is needed for each pathogen. To this aim, we have explored potential of molecules such as β-glucans, flagellin, CpG and bacterial lipopolysacharide (LPS) as oral adjuvants. For this, we have determined the effects of these adjuvants ex vivo in rainbow trout intestine tissue sections, and in vitro in leucocytes isolated from rainbow trout spleen and intestine. The effects were evaluated by analyzing the levels of transcription of different genes related to the innate and adaptive immune response, as well as evaluating the number of IgM-secreting cells. LPS seems to be the molecule with stronger immunostimulatory potential, and could safely be used as a mucosal adjuvant in rainbow trout. Moreover, the designed strategy provides a fast methodology to screen adjuvants that are suitable for oral vaccination, providing us with valuable information about how the intestinal mucosa is regulated in fish., This work was financed by the Spanish Ministry of Science, 2016 725061 TEMUBLYM Innovation and Universities (projects AGL2017-85494-C2-1-R and PID2020-113268RB-I00), by the Comunidad de Madrid (grant 2016-T1/BIO-1672 ) and the European Research Council (ERC Consolidator Grant ).

Trained immunity defines long-term memory of innate immunity based on transcriptional, epigenetic, and metabolic modifications of myeloid cells, which are characterized by elevated proinflammatory responses toward homologous or heterologous secondary stimuli in mammals. However, the evidence of trained immunity-associated immune cells and its molecular mechanism in teleost fish remains largely unknown. In this study, we established a trained immunity activation model in turbot (Scophthalmus maximus) and found that administration with β-glucan induces protection against a bacterial infection. Through single-cell RNA sequencing to annotate 14 clusters of innate and adaptive immune cells, as well as two clusters of blood cells, from head kidney and spleen, respectively, we characterized that neutrophil displays cardinal features of trained immunity by analyzing the expression abundance of trained immunity database–related genes at the single-cell level. Subsequently, through establishing an in vivo training and in vitro neutrophil challenge model, we found that the trained neutrophils exhibit a significant elevation of the IL-1R signaling pathway after Edwardsiella piscicida infection. Furthermore, inhibition of neutrophil’s IL-1R signaling pathway through anakinra treatment impaired the heightened production of reactive oxygen, nitrogen species, lactate, as well as the neutrophil extracellular traps formation and bacterial killing ability. Taken together, these findings characterized neutrophil as the orchestrator to express features of trained immunity, and revealed that the IL-1R signaling pathway plays a critical role in induction of trained immunity for bacterial clearance in teleost fish.

The aim of this study was to examine the combined effects of sulfated β-Glucan from Saccharomyces cerevisiae (sGSC) on growth performance, antioxidant ability, nonspecific immunity, and intestinal flora of the red swamp crayfish (Procambarus clarkii). Four experimental diets (sGSC25, sGSC50, sGSC100 and sGSC200) with different levels of sGSC (0.025%, 0.05%, 0.1% and 0.2% in diet, respectively) were fed to juvenile crayfish (average weight: 2.5 ± 0.5 g) for 8 weeks. The control diet was given with 2000 mg/kg GSC (GSC200 group). The based control diet was given without sGSC or GSC (blank group). Each group had 3 parallel test pools, 20 crayfish were reared in each pool. At the end of the growth trial, adding dietary 0.025%-0.1% sGSC could significantly improve the growth performance, antioxidant capacity and immunity of crayfish. Compared with GSC, sGSC had a better effect at lower concentration. Higher concentration of sGSC (0.1%) would cause some side effects. sGSC also could improve the structure of the intestinal flora and optimize the function of the flora. sGSC would increase the abundances of probiotics such as Hafnia and Acinetobacter, and decreases the abundances of maleficent bacteria such as Enterobacteriaceae. Higher concentration of sGSC (0.1%) would increase the abundance of Aeromonas. To conclude, 0.025%-0.1% sGSC can be used as a supplement in crayfish feed to increase growth, immunity, and antioxidant capacity and improve the structure of intestinal flora. These results provided a theoretical basis for the application of sGSC instead of GSC in crayfish breeding. It will be necessary to further study the optimal concentration of sGSC in feed additives in different growth stages of crayfish in the future.

This study investigated the adsorption behavior of Pb

In the present study, we studied the effect of β-glucan on the activation of antiviral immune responses against nervous necrosis virus (NNV) taking into consideration the role of innate immune training. Sevenband grouper primary macrophages showed an attenuated proinflammatory response and elevated antiviral response to NNV infection. In vitro, priming of β-glucan enhanced macrophage viability against NNV infection which is associated with the activation of sustained inflammatory cytokines gene expression. Observations were clear to understand that NLR Family CARD Domain Containing 3 (NLRC3) and caspase-1 activation and subsequent IL-1β production were reduced in β-glucan-primed macrophages. Subsequent markers for training including Lactate and abundance of HIF-1α were elevated in the cells following training. However, the lactate dehydrogenase (LDH) concentrations remained stable among the β-glucan stimulated infected and uninfected groups suggesting similar macrophage health in both groups. In vivo, the NNV-infected fish primed with β-glucan had a higher survival rate (60%) than the control NNV-infected group (40%). Our findings demonstrate that β-glucan induced protective responses against NNV infection and studies are underway to harness its potential applicability for prime and boost vaccination strategies.

Trained immunity and tolerance are part of the innate immune memory that allow innate immune cells to differentially respond to a second encounter with stimuli by enhancing or suppressing responses. In trained immunity, treatment of macrophages with β-glucan (BG) facilitates the production of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. For the tolerance response, LPS stimulation leads to suppressed inflammatory responses during subsequent LPS exposure. Epigenetic reprogramming plays crucial roles in both phenomena, which are tightly associated with metabolic flux. In this study, we performed a screening of an epigenetics compound library that affects trained immunity or LPS tolerance in macrophages using TNFα as a readout. Among the 181 compounds tested, one compound showed suppressive effects, while 2 compounds showed promoting effects on BG-trained TNFα production. In contrast, various inhibitors targeting Aurora kinase, histone methyltransferase, histone demethylase, histone deacetylase and DNA methyltransferase showed inhibitory activity against LPS tolerance. Several proteins previously unknown to be involved in innate immune memory, such as MGMT, Aurora kinase, LSD1 and PRMT5, were revealed. Protein network analysis revealed that the trained immunity targets are linked via Trp53, while LPS tolerance targets form three clusters of histone-modifying enzymes, cell division and base-excision repair. In trained immunity, the histone lysine methyltransferase SETD7 was identified, and its expression was increased during BG treatment. Level of the histone lysine demethylase, LSD1, increased during LPS priming and siRNA-mediated reduction resulted in increased expression of Il1b in LPS tolerance. Taken together, this screening approach confirmed the importance of epigenetic modifications in innate immune memory and provided potential novel targets for intervention.

Yeast β-glucan BYG that isolated from OM β-1,6-glucanase GluM-based hydrolysis exhibits structural integrity that responsible for its favorable immunomodulatory activity.

Oral delivery remains one of the most convenient routes for drug administration compared to intravenous, intramuscular, and via suppositories. However, due to the risk of degradation, and proteolysis of molecules in the acidic gastric medium, as well as the difficulty of transporting large molecules through the intestinal membrane, more than half of the therapeutic molecules are prohibited for oral administration. Moreover, most of the large molecules and biological therapeutics are not available in oral dosage form due to their instability in the stomach and inability of intestinal absorption. To achieve expected bioavailability, an orally administered therapeutic molecule must be protected within the stomach, and transportation facilitated via the small intestine. In this project, we have introduced a hybrid carrier, composed of Taurocholic Acid (TA) and β-Glucan (TAG), that is shown to be effective for the simultaneous protection of the biologics in acidic buffer and simulated gastric juice as well as facilitate enhanced absorption and transportation via the small intestine. In this project, we have used an eGFP encoded plasmid as a model biologic to prepare particles mediated with TAG. TAG show the potential of enhancing transfection and expression of eGFP as we have observed two fold higher expression in the cell upon coincubation for 4 h. In vivo studies on orally dosed mice showed that eGFP expression in the liver was significantly higher in TAG containing particles compared to particles without TAG. The findings suggest that the TAG carrier is capable of not only preserving biologics but also transporting them more efficiently to the liver. As a result, this strategy can be employed for a variety of liver-targeted therapeutic delivery to treat a variety of liver diseases.

β-glucan derived from the black yeast Aureobasidium pullulans (A. pullulans) is one of the natural products attracting attention due to its high potential for application as a functional food and pharmaceutical. Our team of researchers obtained a highly soluble, low-molecular-weight β-glucan from the fermentation culture medium of A. pullulans via mechanochemical ball milling method, that is, the low-molecular-weight A. pullulans-fermented β-D-glucan (LMW-AP-FBG). We investigated the anti-inflammatory effect of LMW-AP-FBG using lipopolysaccharide (LPS)-stimulated murine macrophages (RAW264.7 cells) in the current study. LMW-AP-FBG altered LPS-stimulated inflammatory responses by reducing the release of inflammatory mediators such as nitric oxide (NO), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. As well, the mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) signaling pathways were downregulated by LMW-AP-FBG. Furthermore, LMW-AP-FBG markedly reduced LPS-induced expression of cell surface molecules, CD14, CD86, and MHC class II, which mediate macrophage activation. These findings suggest that LMW-AP-FBG can be used as an effective immune modulator to attenuate the progression of inflammatory disease.

β-glucan is an important functional active component with relatively high content in barley. It is reported to possess various biological activities, including anti-oxidative stress, but its mechanism of action remains obscure. In the current study, C. elegans was used as an in vivo animal model to explore its anti-oxidative stress mechanism. We found that both RBG (raw barley β-glucan) and FBG (fermented barley β-glucan) could significantly reduce the ROS level in C. elegans under oxidative emergency conditions. In addition, both FBG and RBG had positive effects on SOD and CAT enzyme activity, and FBG treatment obviously reduced the MDA content in nematodes under oxidative stress. Moreover, FBG and RBG pretreatment could extend the median lifespan of C. elegans under oxidative stress. The CB1370 and CF1038 mutants further confirmed that daf-2 and daf-16 were necessary for FBG or RBG to participate in anti-oxidative stress, and the RT-PCR results also evidenced that β-glucans resist oxidative stress in C. elegans partially through the daf-2/daf-16 pathway. In summary, barley β-glucan has high potential to defense oxidative stress as a natural polysaccharide.

To relieve the severe economic and social burdens and patient suffering caused by the increasing incidence of chronic wounds, more effective treatments are urgently needed. In this study, we focused on developing a novel sprayable wound dressing with the active ingredient β-1,3/1,6-glucan (βG). Since βG is already available as the active ingredient in a commercial wound healing product provided as a hydrogel in a tube (βG-Gel), the sprayable format should bring clinical benefit by being easily sprayed onto wounds; whilst retaining βG-Gel’s physical stability, biological safety and wound healing efficacy. Potentially sprayable βG hydrogels were therefore formulated, based on an experimental design setup. One spray formulation, named βG-Spray, was selected for further investigation, as it showed favorable rheological and spraying properties. The βG-Spray was furthermore found to be stable at room temperature for more than a year, retaining its rheological properties and sprayability. The cytotoxicity of βG-Spray in keratinocytes in vitro, was shown to be promising even at the highest tested concentration of 100 μg/ml. The βG-Spray also displayed favorable fluid affinity characteristics, with a capacity to both donate and absorb close to 10% fluid relative to its own weight. Finally, the βG-Spray was proven comparably effective to the commercial product, βG-Gel, and superior to both the water and the carrier controls (NoβG-Spray), in terms of its ability to promote wound healing in healing-impaired animals. Contraction was found to be the main wound closure mechanism responsible for the improvement seen in the βG-treatment groups (βG-Spray and βG-Gel). In conclusion, the novel sprayable βG formulation, confirmed its potential to expand the clinical use of βG as wound dressing.

The effect of dietary β-glucan on seminal plasma composition, sperm characteristics, expression of aquaporins, and antioxidative defence genes of golden mahseer was evaluated. For that, four experimental diets containing 0 (control), 0.5, 1, and 1.5% β-glucan were fed to male golden mahseer brooders for 130 days. Feeding of 0.5% β-glucan was found to improve sperm characteristics, viz. sperm count, motility, viability, and morphology with no effect on gonadosomatic index and seminal plasma energy resources. The marked down-regulation in the transcript abundance of testicular aqp3a noticed in 1.5% β-glucan fed brooders corresponds to their poor sperm quality. Further, the mRNA expression of genes encoding antioxidant enzymes, namely gst and sod1, was lowest in 0.5% β-glucan fed brooders. In contrast, control and higher β-glucan (1 and 1.5%) groups displayed relatively higher expression levels of testicular gst and sod1. On the other hand, the higher seminal plasma total antioxidant capacity observed in 0.5 and 1% β-glucan fed brooders indicated increased scavenging ability of reactive oxygen species. Overall, supplementation of 0.5% β-glucan improved sperm quality and antioxidative potential, but the higher inclusion (1.5%) negatively affected sperm characteristics. Collectively, dietary β-glucan (0.5%) can be a practical approach to developing quality broodstock of golden mahseer.

Bacterial infections are a common and deadly threat to vulnerable patients. Alternative strategies to fight infection are needed. β-Glucan, an immunomodulator derived from the fungal cell wall, provokes resistance to infection by inducing trained immunity, a phenomenon that persists for weeks to months. Given the durability of trained immunity, it is unclear which leukocyte populations sustain this effect. Macrophages have a life span that surpasses the duration of trained immunity. Thus, we sought to define the contribution of differentiated macrophages to trained immunity. Our results show that β-glucan protects mice from Pseudomonas aeruginosa infection by augmenting recruitment of innate leukocytes to the site of infection and facilitating local clearance of bacteria, an effect that persists for more than 7 d. Adoptive transfer of macrophages, trained using β-glucan, into naive mice conferred a comparable level of protection. Trained mouse bone marrow–derived macrophages assumed an antimicrobial phenotype characterized by enhanced phagocytosis and reactive oxygen species production in parallel with sustained enhancements in glycolytic and oxidative metabolism, increased mitochondrial mass, and membrane potential. β-Glucan induced broad transcriptomic changes in macrophages consistent with early activation of the inflammatory response, followed by sustained alterations in transcripts associated with metabolism, cellular differentiation, and antimicrobial function. Trained macrophages constitutively secreted CCL chemokines and robustly produced proinflammatory cytokines and chemokines in response to LPS challenge. Induction of the trained phenotype was independent of the classic β-glucan receptors Dectin-1 and TLR-2. These findings provide evidence that β-glucan induces enhanced protection from infection by driving trained immunity in macrophages.

An eight-week feeding trial was performed to assess the effect of different dietary levels (0, 0.5, 1.0, and 1.5%) of β-glucan (sourced from Saccharomyces cerevisiae) on growth, survival, immunological parameters (immune gene expression, lysozyme, and antiprotease), total antioxidant status, thermal tolerance, and disease resistance of Tor putitora fry. Feeding of moderate doses (0.5 and 1.0%) of β-glucan significantly improved survival but not weight gain percentage as compared to that received unsupplemented control and highest dose (1.5%) of glucan. Supplementation of β-glucan in diets differentially influenced the mRNA expression of cytokine and other immune genes. For instance, transcripts of cytokines such as tnf-α and il-1β were significantly upregulated, while ifn-γ and il-10 were unaffected by β-glucan intake. Also, the relative mRNA expression of tlr-5 and hepcidin1 along with lysozyme and antiprotease activities were remained largely unchanged by dietary glucan administration. In contrast, β-glucan induced mRNA expression of defensin1 and c3 while decreased the transcript level of mhc-1. On the other hand, dietary inclusion of β-glucan markedly improved total antioxidant levels and extended the thermal tolerance limits at both the ends, as shown by increased CTmax and lower CTmin than the control group. After feeding β-glucan for eight weeks, the fish were bath challenged with a bacterial pathogen, Aeromonas salmonicida. The challenge study results revealed that β-glucan intake improved most of the studied immune parameters, resulting in lower mortality. Overall, dietary inclusion of β-glucan (0.5-1.0%) was efficient in improving the immune responses, thermal tolerance, and disease resistance of T. putitora fry.

The largest living rodent, capybara, can efficiently depolymerize and utilize lignocellulosic biomass through microbial symbiotic mechanisms yet elusive. Herein, we elucidate the microbial community composition, enzymatic systems and metabolic pathways involved in the conversion of dietary fibers into short-chain fatty acids, a main energy source for the host. In this microbiota, the unconventional enzymatic machinery from Fibrobacteres seems to drive cellulose degradation, whereas a diverse set of carbohydrate-active enzymes from Bacteroidetes, organized in polysaccharide utilization loci, are accounted to tackle complex hemicelluloses typically found in gramineous and aquatic plants. Exploring the genetic potential of this community, we discover a glycoside hydrolase family of β-galactosidases (named as GH173), and a carbohydrate-binding module family (named as CBM89) involved in xylan binding that establishes an unprecedented three-dimensional fold among associated modules to carbohydrate-active enzymes. Together, these results demonstrate how the capybara gut microbiota orchestrates the depolymerization and utilization of plant fibers, representing an untapped reservoir of enzymatic mechanisms to overcome the lignocellulose recalcitrance, a central challenge toward a sustainable and bio-based economy. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published

Introduction: As a supplement, beta-glucan has various therapeutic healing effects generated by the immune cells. It has been scientifically approved and proven to be a biological defense modifier. The aim of this study was to investigate the effects of beta-glucan on treatments administered in an acute otitis media model Objectives: This study investigated the effect of beta-glucan on the treatment of acute otitis media in an acute otitis media -induced animal model. Efficacy was evaluated both immunologically and histologically. Methods: The study sample comprised 35 adult rats, randomly separated into 5 groups of 7: Group 1 (control), Group 2 (acute otitis media, no treatment), Group 3 (acute otitis media + antibiotic), Group 4 (acute otitis media + beta-glucan) and Group 5 (acute otitis media + beta-glucan + antibiotic). Analyses were made of the histopathology and immunology examination results in respect of thickening of the tympanic membrane, epithelium damage, inflammation, and sclerosis. In all groups the serum levels of TNF-α, IL-4, IL-6 and IL-1β were evaluated. Results: All serum cytokine levels were significantly lower in the beta-glucan and antibiotictreated groups compared to the acute otitis media Group. Significant differences in tympanic membrane thickness, inflammation, epithelium damage, and sclerosis values were observed between the acute otitis media + antibiotic and acute otitis media + beta-glucan Groups. According to these parameters, the values in aute otitis media + antibiotic + beta-glucan Group were markedly lower than those of the other groups. There was a significant difference in the acute otitis media + antibiotic + beta-glucan Groups compared to acute otitis media Group (p < 0.001). Conclusions: Both antibiotic and beta-glucan treatment reduced acute otitis media signs of inflammations in an acute otitis media-induced rat model, decreasing histological damage and cytokine levels. Co-administration of antibiotic and beta-glucan led to a significant reduction in tympanic membrane thickness, inflammation, and epithelium damage. Antibiotic + beta-glucan treatment resulted in a greater decrease in tympanic membrane thickness, inflammation, and epithelium damage than in the other groups. From these results, it can be suggested that beta-glucan, in combination with antibiotics may provide an alternative for the treatment of acute otitis media. Resumo Introdução: Como suplemento, o beta-glucano apresenta vários efeitos terapêuticos gerados pelas células imunológicas. Cientificamente aprovado, mostrou ser um modificador de defesa biológica. Objetivo: Investigar os efeitos do beta-glucano nos tratamentos administrados em um modelo de otite média aguda induzida em um modeloanimal. A eficácia foi avaliada imunológica e histologicamente. Método: A amostra do estudo foi composta por 35 ratos adultos, divididos aleatoriamente em 5 grupos de 7: grupo 1 (controle), grupo 2 (otite média aguda, sem tratamento), grupo 3 (otite média aguda + antibiótico), grupo 4 (otite média aguda + beta-glucano) e grupo 5 (otite média aguda + beta-glucano + antibiótico). Foram feitas análises dos resultados dos exames histopatológicos e imunológicos em relação ao espessamento da membrana timpânica, dano ao epitélio, inflamação e esclerose. Os níveis séricos de TNF-α, IL-4, IL-6 e IL-β foram avaliados em todos os grupos. Resultados: Todos os níveis séricos de citocinas foram significativamente mais baixos nos grupos tratados com beta-glucano e antibióticos em comparação com o grupo otite média aguda. Diferenças significativas na espessura da membrana timpânica, inflamação, dano do epitélio e esclerose foram observadas entre os grupos otite média aguda + antibiótico e otite média aguda + beta-glucano. De acordo com esses parâmetros, os valores no grupo otite média aguda + antibiótico + beta-glucano foram acentuadamente inferiores aos dos demais grupos. Houve uma diferença significante no grupo otite média aguda + antibiótico + beta-glucano em comparação ao grupo otite média aguda (p < 0,001). Conclusão: Ambos os tratamentos com antibiótico e com beta-glucano reduziram os sinais de inflamação da otite média aguda em um modelo de rato com otite média aguda induzida, diminuíram os danos histológicos e os níveis de citocinas. A administração concomitante de antibiótico e beta-glucano levou a uma redução significativa na espessura da membrana timpânica, inflamação e danos ao epitélio. O tratamento com antibióticos + beta-glucano resultou em maior diminuição na espessura da membrana timpânica, inflamação e danos no epitélio do que nos outros grupos. A partir desses resultados, pode-se sugerir que o beta-glucano, em combinação com antibióticos, pode fornecer uma opção para o tratamento da otite média aguda.

Cationic polysaccharides have shown excellent ability of nucleic acids delivery. However, cationic curdlan derivatives with high degree of amination cause damage to the cell membrane and induce considerable cytotoxicity, limiting their in vivo application. Herein, we synthesized PEGylated 6-amino-6-deoxy-curdlan derivatives containing cleavable disulfide bonds. The resulting polymers (denote 6AC-2S PEGx) not only showed high affinity to siRNA but also exhibited significantly decreased cytotoxicity and hemolysis effect, while showing remarkable in vitro transfection efficiency. In vivo study demonstrated that 6AC-2S PEG40, which had a lower LD50 value than that of 6AC-100, did not cause liver damage, as the i.v. injection of 6AC-2S PEG40 to mouse did not increase serum level of ALT/AST. Furthermore, tissue distribution results showed that 6AC-2S PEG40 successfully delivered siRNA to liver, lung and spleen. Collectively, our data confirmed that PEGylation can increase the biocompatibility of cationic curdlan derivatives, which is a promising carrier for nucleic acid therapeutics.

application/pdf, Journal of Materials Chemistry B. 2021, 9 (37), P.7713-7724

Programmed death ligand 1 (PD-L1) has been shown to be inducibly expressed on neutrophils to suppress host immunity during polymicrobial sepsis, virus and parasite infections. However, the role of PD-L1 on neutrophil-mediated antifungal immunity remains wholly unknown. Here, we show that the expression of PD-L1 on murine and human neutrophils was upregulated upon the engagement of C-type lectin receptor Dectin-1 with its ligand β-glucans, exposed on fungal pathogen Candida albicans yeast. Moreover, β-glucan stimulation induced PD-L1 translocation into nucleus to regulate the production of chemokines CXCL1 and CXCL2, which control neutrophil mobilization. Importantly, C. albicans infection-induced expression of PD-L1 leads to neutrophil accumulation in bone marrow, through mediating their autocrine secretion of CXCL1/2. Furthermore, neutrophil-specific deficiency of PD-L1 impaired CXCL1/2 secretion, which promoted neutrophil migration from bone marrow into the peripheral circulation, thereby conferring host resistance to C. albicans infection. Finally, either PD-L1 blockade or pharmacological inhibition of PD-L1 expression significantly increased neutrophil release from bone marrow to enhance host antifungal immunity. Our data together indicate that activation of Dectin-1/PD-L1 cascade by β-glucans inhibits neutrophil release from bone marrow reserve, contributing to the negative regulation of antifungal innate immunity, which functions as a potent immunotherapeutic target against life-threatening fungi infections.

β-glucan has been used as immunostimulant for fish. However, the effect of yeast β-glucan on viral infections has been less studied in fish. In this study, we investigated the effects of β-glucan on the resistance of zebrafish against spring viraemia of carp virus (SVCV) and elucidated the underlying mechanisms. Zebrafish were fed with a control diet or diet supplemented with 0.01% and 0.025% β-glucan for 2 weeks, and were challenged by SVCV. Zebrafish embryonic fibroblast (ZF4) cells were treated with 5 μg/mL β-glucan and were infected by SVCV. We further investigated the effect of β-glucan on autophagy level post SVCV infection. The intestinal microbiota was evaluated by 16S rRNA gene pyrosequencing. Results showed that dietary supplementation of 0.025% β-glucan significantly increased survival rate of zebrafish compared with control group after SVCV challenge (P < 0.05). Dietary β-glucan significantly increased the expression of genes related to type I IFN antiviral immune pathway in the spleen of zebrafish after viral infection, including type I IFN genes (ifnφ1, ifnφ2, ifnφ3), IFN-stimulated genes (mxb, mxc), as well as other genes involved in the IFN signaling pathway, including tlr7, rig1, mavs, irf3 and irf7. Morpholino knockdown of type I IFN receptors dampened the antiviral effect of β-glucan in zebrafish larvae, indicating that β-glucan-mediated antiviral function was at least partially dependent on IFN immune response. Furthermore, β-glucan can inhibit the replication of SVCV in ZF4 cells. However, β-glucan did not stimulate type I IFN antiviral response in ZF4 cells, and the antiviral effect of β-glucan in ZF4 was independent of Myd88. Interestingly, β-glucan induced autophagy in ZF4 cells after SVCV infection. Inhibition of autophagy blocked the antiviral effect of β-glucan in ZF4 cells. Lastly, dietary β-glucan changed the composition of intestinal microbiota in zebrafish, with reduced abundance of Proteobacteria and an enrichment of Fusobacteria and Firmicutes. To sum up, our results indicate that the β-glucan enhanced resistance of zebrafish against SVCV and the mechanism involved stimulation of type I IFN antiviral immune response of fish after viral infection.

ScopeGut microbiota alterations are associated with obesity and type 2 diabetes. Yeast β-glucans are potential modulators of the innate immune-metabolic response, by impacting glucose, lipid, and cholesterol homeostasis. The study examines whether yeast β-glucan interacts differentially with either an obese healthy or obese diabetic gut microbiome, to impact metabolic health through hepatic effects under high-fat dietary challenge.Methods and resultsMale C57BL/6J mice are pre-inoculated with gut microbiota from obese healthy (OBH) or obese type 2 diabetic (OBD) subjects, in conjunction with a high-fat diet (HFD) with/without yeast β-glucan. OBD microbiome colonization adversely impacts metabolic health compared to OBH microbiome engraftment. OBD mice are more insulin resistant and display hepatic lipotoxicity compared to weight matched OBH mice. Yeast β-glucan supplementation resolves this adverse metabolic phenotype, coincident with increasing the abundance of health-related bacterial taxa. Hepatic proteomics demonstrates that OBD microbiome transplantation increases HFD-induced hepatic mitochondrial dysfunction, disrupts oxidative phosphorylation, and reduces protein synthesis, which are partly reverted by yeast β-glucan supplementation.ConclusionsHepatic metabolism is adversely affected by OBD microbiome colonization with high-fat feeding, but partially resolved by yeast β-glucan. More targeted dietary interventions that encompass the interactions between diet, gut microbiota, and host metabolism may have greater treatment efficacy.

Salecan, a natural β-glucan consisting of seven residues linked by β-(1→3)/α-(1→3) glycosidic bonds, is one of the novel food ingredients approved in China. β-Glucan has a variety of health-improving effects, yet its mechanism against liver injury remains poorly understood. β-Glucan can induce shifts in the gut microbiota and show health benefits; however, whether modulation of the gut microbiota by β-glucan is associated with its benefits remains unclear. Here, the hepatoprotective effect and potential mechanism of salecan supplementation using a model of CCl

Soybean meal evokes diet-induced intestinal inflammation in certain fishes. Although the molecular aspects of soybean-induced intestinal inflammation in zebrafish are known, the impact of the inflammatory diet on fish behavior remain largely underexplored. We fed zebrafish larvae with three diets - control, soybean meal and soybean meal with β-glucan to gain deeper insight into the behavioral changes associated with the soybean meal-induced inflammation model. We assessed the effect of the diets on the locomotor behavior, morphological development, oxygen consumption and larval transcriptome. Our study revealed that dietary soybean meal can reduce the locomotor activity, induce developmental defects and increase the oxygen demand in zebrafish larvae. Transcriptomic analysis pointed to the suppression of genes linked to visual perception, organ development, phototransduction pathway and activation of genes linked to the steroid biosynthesis pathway. On the contrary, β-glucan, an anti-inflammatory feed additive, counteracted the behavioral and phenotypic changes linked to dietary soybean. Although we did not identify any differentially expressed genes from the soybean meal alone fed group vs soybean meal + β-glucan-fed group comparison, the unique genes from the comparisons of the two groups with the control likely indicate reduction in inflammatory cytokine signaling, inhibition of proteolysis and induction of epigenetic modifications by the dietary glucan. Furthermore, we found that feeding an inflammatory diet at the larval stage can lead to long-lasting developmental defects. In conclusion, our study reveals the extra-intestinal manifestations associated with soybean meal-induced inflammation model.

Non-alcoholic fatty liver disease (NAFLD) has become a public health burden. Controlling bile acids (BAs) metabolism and energy expenditure are potential therapies for NAFLD. Because one of the main health effects of cereal β-glucan (BG) is its ability to lower cholesterol by interacting with BAs, BG may regulate imbalances of the metabolism of BAs during NAFLD. Therefore, by using metabolic tests coupled with the profiling of hepatic BAs, we have assessed the effect of BG from highland barley on western diet (WD) induced NAFLD mice. BG treatment prevented fat accumulation and increased adipose lipolysis. These moderating effects were associated with an increased energy expenditure. Moreover, BG-treated mice enhanced the production of hepatic BAs, which may be connected with the activation of farnesoid X receptor (FXR) signaling in the liver and inhibition of FXR signaling in the ileum. Our results suggest that BG prevents fat accumulation by increasing energy expenditure, a mechanism associated with major changes in the composition of hepatic BAs.

Barley consumption is expected to increase insulin sensitivity by increasing the level of short-chain fatty acids (SCFAs) and promoting the secretion of GLP-1. However, the involvement of GPR43, a receptor for SCFAs, has not been investigated. Therefore, we evaluated whether the inhibitory effect of β-glucan-rich barley intake on blood glucose rise is mediated by GPR43 signalling

Oat β-glucan (OBG) and L-arabinose (LA) have exhibited positive effects on diabetes and its complications. However, it is unclear whether OBG and LA have a synergistic effect. We investigated the effect of variable compositions (OBG : LA = 1 : 1, 1 : 2, 1 : 4,1 : 6, 1 : 8, 1 : 10, 2 : 1, 4 : 1, 6 : 1, 8 : 1, 10 : 1) on glucose uptake in IR-HepG2 cells induced by dexamethasone (DEX) to find out the optimal composition showing synergistic effects. Furthermore, this study evaluated the anti-diabetic activity of the optimal composition in db/db mice.

Non-functional scars commonly form after cutaneous injuries. At present, most clinical treatments for scar eradication typically have long treatment courses, low curative effects, and are expensive. In this research, three hydrogels, namely chitin hydrogel, β-glucan hydrogel, and hybrid hydrogel composed of chitin and β-glucan, were successfully prepared, and they exhibited good shear thinning property and bioadhesiveness. In a full-thickness skin defect mouse model, the three hydrogels were found to effectively promote wound closure and inhibit scar formation. Through the immunohistochemistry staining and immunofluorescence staining of the wound tissues, the hydrogels could significantly promote the formation of collagen III, the regeneration of hair follicles, and the expression of keratin K14 and K15. They could also regulate the production of VEGF and immune factors such as IL-10 and IL-12, and inhibit the expression of the fibroblast regulatory factor En-1 in the wound site, which correlated well with their improved wound healing promoting effect and anti-scarring effect. Among all the hydrogels, the hybrid hydrogel was the best to promote wound healing and inhibit scarring. This study, for the first time, proved the excellent therapeutic effect of chitin and β-glucan hydrogels in the management of wound healing and skin regeneration without scar formation, which will lay a solid foundation for the development of skin regeneration medication and future clinical transformation.

The article systematizes information about the sources of β-glucan, its technological functions and practical aspects of its use in dairy and milk-based products. According to the analysis of scientific information, the main characteristics of β-glucan classifications were considered: the source of origin, chemical structure, and methods of obtention. It has been established that the most popular in the food technology of dairy products are β-glucans from oat and barley cereal, which exhibit pronounced technological functions in the composition of dairy products (gel formation, high moisture-binding capacity, increased yield of finished products, formation of texture, and original sensory indicators). The expediency of using β-glucan from yeast and mushrooms as a source of biologically active substances that ensure the functional orientation of the finished product has been revealed. For the first time, information on the use of β-glucan of various origins in the most common groups of dairy and milk-based products has been systematized. The analytical review has scientific and practical significance for scientists and specialists in the field of food production, in particular dairy products of increased nutritional value.

Prebiotics are nondigestible food agents that stimulate the growth of bacteria in the gut, whereas probiotics are live microorganisms that replace or restore beneficial bacteria in the digestive tract. Both agents have been shown to have beneficial qualities within the microbiota-gut-brain axis, but the behavioural effects of prebiotics have been less studied than probiotics. Whereas several studies have shown that prebiotics reduce inflammation and modulate anxiety in animals that are injected with lipopolysacccharides or chronically stressed animals, respectively, it is not yet known how they affect a healthy organism. Here, we tested the behavioural effects of galacto-oligosaccharides and beta glucan as a commercially available prebiotic blend in healthy, naïve Sprague-Dawley rats. We used the open field test and elevated plus maze to assess anxiety-like behaviour in controls and in rats that ingested the prebiotic blend in their drinking water. We also used the Morris Water Maze to assess spatial memory performance in controls and prebiotic treated rats. Rats treated with prebiotics spent more time in the intermediate zone of the open field test and in the open arms of the elevated plus maze, and exhibited a shorter latency to enter each of these zones. No significant differences between groups were found in the Morris Water Maze. Our results suggest that whereas prebiotics significantly reduced anxiety-like behaviours, it had no effect on spatial memory performance. Altogether, our data indicate that commercially available prebiotic beta glucan blends have anxiolytic effects in healthy rats.