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Molecular Nutrition & Food Research Jan 2021The innate immune system responds in a rapid and non-specific manner against immunologic threats; inflammation is part of this response. This is followed by a slower but... (Review)
Review
The innate immune system responds in a rapid and non-specific manner against immunologic threats; inflammation is part of this response. This is followed by a slower but targeted and specific response termed the adaptive or acquired immune response. There is emerging evidence that dietary components, including yeast-derived β-glucans, can aid host defense against pathogens by modulating inflammatory and antimicrobial activity of neutrophils and macrophages. Innate immune training refers to a newly recognized phenomenon wherein compounds may "train" innate immune cells, such that monocyte and macrophage precursor biology is altered to mount a more effective immunological response. Although various human studies have been carried out, much uncertainty still exists and further studies are required to fully elucidate the relationship between β-glucan supplementation and human immune function. This review offers an up-to-date report on yeast-derived β-glucans as immunomodulators, including a brief overview of the current paradigm regarding the interaction of β-glucans with the immune system. The recent pre-clinical work that has partly decrypted mode of action and the newest evidence from human trials are also reviewed. According to pre-clinical studies, β-1,3/1,6-glucan derived from baker's yeast may offer increased immuno-surveillance, although the human evidence is weaker than that gained from pre-clinical studies.
Topics: Age Factors; Animals; Athletes; Glucans; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunologic Factors; Lectins, C-Type; Respiratory Tract Infections; beta-Glucans
PubMed: 32223047
DOI: 10.1002/mnfr.201901071 -
Nutrients Dec 2021Many articles and manuscripts focusing on the structure, function, mechanism of action, and effects of β-glucan have been published recently [...].
Many articles and manuscripts focusing on the structure, function, mechanism of action, and effects of β-glucan have been published recently [...].
Topics: Dietary Fiber; Food Analysis; Health Promotion; Humans; Nutritive Value; beta-Glucans
PubMed: 35010971
DOI: 10.3390/nu14010096 -
Cell Oct 2020Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary...
Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with β-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth. The anti-tumor effect of β-glucan-induced trained immunity was associated with transcriptomic and epigenetic rewiring of granulopoiesis and neutrophil reprogramming toward an anti-tumor phenotype; this process required type I interferon signaling irrespective of adaptive immunity in the host. Adoptive transfer of neutrophils from β-glucan-trained mice to naive recipients suppressed tumor growth in the latter in a ROS-dependent manner. Moreover, the anti-tumor effect of β-glucan-induced trained granulopoiesis was transmissible by bone marrow transplantation to recipient naive mice. Our findings identify a novel and therapeutically relevant anti-tumor facet of trained immunity involving appropriate rewiring of granulopoiesis.
Topics: Adaptive Immunity; Adoptive Transfer; Animals; Epigenesis, Genetic; Granulocytes; Immunity, Innate; Interferon Type I; Mice, Inbred C57BL; Monocytes; Neoplasms; Neutrophils; Phenotype; Receptor, Interferon alpha-beta; Transcription, Genetic; Transcriptome; beta-Glucans
PubMed: 33125892
DOI: 10.1016/j.cell.2020.09.058 -
Frontiers in Immunology 2022The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses.... (Review)
Review
The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.
Topics: Lectins, C-Type; Ligands; Phagocytosis; Signal Transduction; beta-Glucans
PubMed: 35237264
DOI: 10.3389/fimmu.2022.812148 -
International Journal of Molecular... Aug 2019β-glucan is a non-starch soluble polysaccharide widely present in yeast, mushrooms, bacteria, algae, barley, and oat. β-Glucan is regarded as a functional food... (Review)
Review
β-glucan is a non-starch soluble polysaccharide widely present in yeast, mushrooms, bacteria, algae, barley, and oat. β-Glucan is regarded as a functional food ingredient due to its various health benefits. The high molecular weight (Mw) and high viscosity of β-glucan are responsible for its hypocholesterolemic and hypoglycemic properties. Thus, β-glucan is also used in the food industry for the production of functional food products. The inherent gel-forming property and high viscosity of β-glucan lead to the production of low-fat foods with improved textural properties. Various studies have reported the relationship between the molecular structure of β-glucan and its functionality. The structural characteristics of β-glucan, including specific glycosidic linkages, monosaccharide compositions, Mw, and chain conformation, were reported to affect its physiochemical and biological properties. Researchers have also reported some chemical, physical, and enzymatic treatments can successfully alter the molecular structure and functionalities of β-glucan. This review article attempts to review the available literature on the relationship of the molecular structure of β-glucan with its functionalities, and future perspectives in this area.
Topics: Food Additives; Pharmaceutic Aids; Viscosity; beta-Glucans
PubMed: 31426608
DOI: 10.3390/ijms20164032 -
Nature Immunology Feb 2023Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of...
Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.
Topics: Animals; Mice; Humans; Trained Immunity; Macrophages; Lysophospholipids; Monocytes; Lung Neoplasms; beta-Glucans; Tumor Microenvironment
PubMed: 36604547
DOI: 10.1038/s41590-022-01388-8 -
Nutrients Aug 2021The prevalence of gastritis in humans is constantly growing and a prediction of an increase in this health problem is observed in many countries. For this reason,... (Randomized Controlled Trial)
Randomized Controlled Trial
The prevalence of gastritis in humans is constantly growing and a prediction of an increase in this health problem is observed in many countries. For this reason, effective dietary therapies are sought that can alleviate the course of this disease. The objective of this study was to determine the effect of chemically pure oat beta-glucan preparations with different molar masses, low or high, used for 30 days in patients with histologically diagnosed chronic gastritis. The study enrolled 48 people of both genders of different ages recruited from 129 patients with a gastritis diagnosis. Before and after the therapy, hematological, biochemical, immunological and redox balance parameters were determined in the blood and the number of lactic acid bacteria and SCFA concentrations in the feces. Our results demonstrated a beneficial effect of oat beta-glucans with high molar mass in chronic gastritis in humans, resulting in reduced mucosal damage and healthy changes in SCFA fecal concentration and peripheral blood serum glutathione metabolism and antioxidant defense parameters. This fraction of a highly purified oat beta-glucan is safe for humans. Its action is effective after 30 days of use, which sheds new light on the nutritional treatment of chronic gastritis.
Topics: Adult; Aged; Avena; Chronic Disease; Double-Blind Method; Fatty Acids, Volatile; Feces; Female; Gastritis; Humans; Lactobacillales; Male; Middle Aged; Osmolar Concentration; Treatment Outcome; Young Adult; beta-Glucans
PubMed: 34444949
DOI: 10.3390/nu13082791 -
Journal of Immunology (Baltimore, Md. :... Dec 2021Bacterial infections are a common and deadly threat to vulnerable patients. Alternative strategies to fight infection are needed. β-Glucan, an immunomodulator derived...
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 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.
Topics: Animals; Cell Differentiation; Female; Immunity, Innate; Immunologic Memory; Macrophages; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protective Agents; beta-Glucans
PubMed: 34740960
DOI: 10.4049/jimmunol.2100107 -
Microbiome Oct 2020"Western" style dietary patterns are characterized by a high proportion of highly processed foods rich in fat and low in fiber. This diet pattern is associated with a...
BACKGROUND
"Western" style dietary patterns are characterized by a high proportion of highly processed foods rich in fat and low in fiber. This diet pattern is associated with a myriad of metabolic dysfunctions, including neuroinflammation and cognitive impairment. β-glucan, the major soluble fiber in oat and barley grains, is fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of cognition and brain function via the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fiber-deficient diet (HFFD).
RESULTS
After long-term supplementation for 15 weeks, β-glucan prevented HFFD-induced cognitive impairment assessed behaviorally by object location, novel object recognition, and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and upregulation of proinflammatory cytokine (TNF-α, IL-1β, and IL-6) mRNA expression. Also, in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signaling for synaptogenesis, improved the synaptic ultrastructure examined by transmission electron microscopy, and increased both pre- and postsynaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining), increased the levels of tight junction proteins occludin and zonula occludens-1, and attenuated bacterial endotoxin translocation. The HFFD resulted in microbiota alteration, effects abrogated by long-term β-glucan supplementation, with the β-glucan effects on Bacteroidetes and its lower taxa particularly striking. Importantly, the study of short-term β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention abrogated β-glucan's effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior.
CONCLUSION
This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns. Video Abstract.
Topics: Animals; Brain; Cognitive Dysfunction; Diet, High-Fat; Dietary Fiber; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Obesity; beta-Glucans
PubMed: 33008466
DOI: 10.1186/s40168-020-00920-y -
Cell Reports May 2020β-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called "trained immunity," resulting in an enhanced host...
β-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called "trained immunity," resulting in an enhanced host response against secondary infections. We investigate whether β-glucan exposure confers protection against pulmonary Mycobacterium tuberculosis (Mtb) infection. β-glucan induces trained immunity via histone modifications at gene promoters in human monocytes, which is accompanied by the enhanced production of proinflammatory cytokines upon secondary Mtb challenge and inhibition of Mtb growth. Mice treated with β-glucan are significantly protected against pulmonary Mtb infection, which is associated with the expansion of hematopoietic stem and progenitor cells in the bone marrow and increased myelopoiesis. The protective signature of β-glucan is mediated via IL-1 signaling, as β-glucan shows no protection in mice lacking a functional IL-1 receptor (IL1R). The administration of β-glucan may be used as a novel strategy in the treatment of mycobacterial infections and possibly as an adjuvant to improve anti-tuberculosis vaccines.
Topics: Animals; Humans; Immunity; Interleukin-1; Mice; Mycobacterium tuberculosis; Signal Transduction; beta-Glucans
PubMed: 32433977
DOI: 10.1016/j.celrep.2020.107634