Article 6: Medicinal Mushrooms and Autoimmune Diseases: A New Approach to Immune System Modulation Autoimmune diseases represent a growing challenge for modern medicine. Conditions such as rheumatoid arthritis, multiple sclerosis, lupus, and autoimmune thyroiditis involve a malfunction of the immune system, which mistakenly attacks the body's own cells and tissues. In this context, medicinal mushrooms are proving to be a valuable ally, thanks to their ability to modulate —and not simply stimulate—immune responses. Immunomodulation vs. Immunostimulation: A Key Distinction Immunomodulators work intelligently: they stimulate the immune system when it's underactive (for example, in infections or tumors), but they can also attenuate the hyperactivity typical of autoimmune conditions. This balance is essential, as simple stimulation could aggravate an autoimmune disease . Clinical classification of immunomodulators In medicine, immunomodulators are divided into: Immunosuppressants : reduce immune activity (used for example in transplants); Immunostimulants : they enhance the immune response; Immunoadjuvants : they amplify the immune response to specific antigens (e.g. in vaccines). Medicinal mushrooms fall into a cross-section, being able to exert multiple and contextual effects , depending on the state of the individual's immune system. Mechanisms involved: modulation from within Several compounds present in mushrooms act through specific receptors: β-glucans , by interacting with Dectin-1 and TLRs , positively influence antigen-presenting cells and cytokine production. Lectins regulate the activity of lymphocytes and macrophages by acting on cell signaling. FIPs are able to rebalance the response between Th1 and Th2, two T cell subtypes involved in autoimmune diseases . This regulatory activity is crucial in cases where the organism tends to “confuse” itself with an external agent. Examples of mushrooms with immunoregulatory action Ganoderma lucidum (Reishi) : lowers systemic inflammation and modulates cytokines (IL-2, IFN-γ), reducing the aggressiveness of the immune system. Lentinula edodes (Shiitake) : Its β-glucan lentinan supports the balance of Th1/Th2 responses. Cordyceps sinensis : has been shown in preclinical studies to improve immune tolerance and reduce autoimmune markers. Trametes versicolor : improves the function of dendritic cells, regulating the activation of T lymphocytes. A natural but powerful strategy The mycotherapy approach is not an alternative to conventional medications, but it can be an effective and safe complement to integrated treatment. Medicinal mushrooms offer a natural option to reduce inflammation, support immune regulation, and improve quality of life in patients with autoimmune diseases. Conclusion Research on medicinal mushrooms opens up promising avenues for the management of autoimmune diseases. Thanks to their ability to selectively modulate the immune system, they represent a valuable resource for promoting balance and well-being. Discover our products Looking for natural support for your immune system? 🔗 Visit our website: www.junlei.it Discover our range of medicinal mushroom supplements designed to support immune balance even in delicate situations such as autoimmune diseases.

Article 5: The Immune System's Superpowers: How Medicinal Mushrooms Strengthen It Naturally In recent years, medicinal mushrooms have gained increasing attention for their extraordinary immunomodulatory properties. This isn't just a matter of tradition or folk remedies: today, science confirms that mushrooms contain bioactive compounds capable of effectively and naturally modulating our immune system. Immunomodulation: What it is and why it's important Unlike immunostimulation (which indiscriminately enhances the immune response), immunomodulation is a more refined and balanced mechanism. It serves to strengthen the immune system when necessary, but also to reduce immune activity in the event of excessive reactions, such as those seen in autoimmune diseases or chronic inflammation. And that's exactly what many medicinal mushrooms do. The 4 Key Compounds of Medicinal Mushrooms Polysaccharides (β-glucans) : Considered the most potent immunomodulators among fungal compounds. They stimulate macrophages, dendritic cells, NK cells, and promote the production of cytokines (TNF, IFN-γ, IL-1). Their structure (e.g., β-1,3-glucans with β-1,6 branches) is crucial for immune activation. Lectins : Proteins that bind to specific sugars on immune cells, modulating cell-cell communication and stimulating the production of protective substances such as nitrite and TNF-α. FIPs (Fungal Immunomodulatory Proteins) : They influence the immune system by binding to TLRs, activating the MAPK and NF-κB pathways, and promoting the differentiation of helper T cells. Terpenes and Terpenoids : Volatile compounds that regulate immune function by affecting gene expression. Ganoderma triterpenoids , for example, are known for their immunomodulatory and antitumor effects. Mechanisms of action: the dialogue between fungi and the immune system Mushrooms activate specific receptors on the surface of immune cells, triggering complex defense responses. The main receptors involved are: Dectin-1 : a pattern recognition receptor present on macrophages and dendritic cells. It recognizes fungal β-glucans, activating the production of inflammatory cytokines and stimulating phagocytosis. It is essential for the antifungal response. CR3 (Complement Receptor 3) : Involved in phagocytosis and the inflammatory response. Interacts with β-glucans to stimulate macrophages and neutrophils. TLRs (Toll-Like Receptors), in particular TLR-2 and TLR-6 : these receptors recognize fungal structures and induce the production of cytokines through the activation of the NF-κB pathway, which is important for the innate immune response. The combined activation of these receptors by fungal compounds generates a coordinated immune response , involving: Increased phagocytic activity ; Production of immune mediators (IL-6, IL-1β, TNF-α); Expression of protective genes ; Enhancement of innate and adaptive immunity . This promotes: Greater efficiency in defending against infections ; A reduction in the chronic inflammatory state ; A rebalancing of the immune system in the presence of dysfunctions. These effects are present in macrophages, monocytes, and neutrophils, triggering the production of cytokines and promoting a coordinated immune response. This promotes: Greater efficiency in defending against infections ; A reduction in the chronic inflammatory state ; A rebalancing of the immune system in the presence of dysfunctions. Why integrate them into your daily routine Supplementing with medicinal mushrooms can naturally strengthen the immune system, helping the body respond better to stress, infections, and inflammation. Ganoderma lucidum (Reishi) : known for its immune-balancing action and anti-inflammatory properties. Lentinula edodes (Shiitake) : stimulates phagocytosis and NK cell activity. Trametes versicolor (Turkey Tail) : Used as immune support in integrative oncology. Conclusion Medicinal mushrooms are a valuable resource for those seeking natural solutions to strengthen their immune system. Thanks to their bioactive compounds, they work intelligently, helping the body regain balance and respond better to internal and external stimuli. Discover our products Do you want to support your natural defenses in an intelligent and natural way? 🔗 Visit our website: www.junlei.it Discover our line of medicinal mushroom supplements, designed to boost your immunity every day.

This scientific article, published in the Journal of Fungi in 2020, explores the immunomodulatory effects of edible and medicinal mushrooms and their bioactive compounds. Different classes of molecules, such as polysaccharides, lectins, fungal immunomodulatory proteins (FIPs), and terpenes, are examined, highlighting their structures, functions, and mechanisms of action. The paper summarizes existing clinical studies and discusses the potential therapeutic applications of these compounds, while also highlighting the challenges and areas requiring further investigation for their broader use in medicine. Finally, the role of genomics in the study of medicinal mushrooms is discussed. What are the main categories of bioactive compounds present in medicinal mushrooms and what immunomodulatory activities do they possess? The main categories of bioactive compounds present in medicinal mushrooms that possess immunomodulatory activities are mainly four: polysaccharides, lectins, fungal immunomodulatory proteins (FIPs), and terpenes and terpenoids. • Polysaccharides: Polysaccharides are among the most frequently reported mushroom-derived bioactive compounds with immunomodulatory activity. These polysaccharides are heterogeneous in sugar composition, backbone structure, degree of branching, conformation, molecular weight, and other physical properties, which influence their bioactivity and mechanism of action. They can be homoglycans or heteroglycans and combine with peptides to form peptidoglycans or polysaccharide-protein complexes. In general, polysaccharides with higher molecular weights exhibit greater bioactivity. Many medicinal mushroom polysaccharides have been shown to stimulate natural killer (NK) cells, macrophages, and dendritic cells, as well as induce the production of cytokines such as TNF, IFN-γ, and IL-1. Specific examples include lentinan from shiitake ( Lentinula edodes ) and schizophyllan from Schizophyllum commune , both β-1,3-D-glucans with β-1,6 branches, which have shown immunomodulatory and antitumor activities and have been approved for clinical use in Japan. Other polysaccharides with immunomodulatory effects are present in several species such as Agaricus blazei , Auricularia auricula-judae , Ganoderma lucidum , Grifola frondosa , Hericium erinaceus , and many others (see Table 24). Mechanisms of action may include activation of the TLR4-NFκB system in macrophages. 5 Structure, including the presence of triple helices in some β-D-glucans such as lentinan and schizophyllan, and chemical modifications such as sulfation, may influence the immunomodulatory activity of polysaccharides. • Lectins: Lectins are proteins that recognize and interact with various carbohydrates/glycoproteins on the cell surface. Medicinal mushroom lectins have been shown to possess specific immunomodulatory, antiproliferative, and antitumor activities. They work by stimulating nitrite production, increasing the expression of TNF-α and interleukins, activating lymphocytes, and promoting the production of macrophage-activating factors. Several mushroom lectins, such as Agaricus bisporus lectin (ABL), Grifola frondosa lectin (GFL), and Schizophyllum commune lectin (SCL), have shown such effects (see Table 310). Some mushroom lectins have also shown antiviral, mitogenic, antimicrobial, and antioxidant activities. • Fungal Immunomodulatory Proteins (FIPs): FIPs are a group of proteins with highly similar amino acid sequences that exist as dimers. FIPs stimulate antigen-presenting cells by binding to Toll-like receptors (TLRs) and releasing cytokines such as NO and IL-1211. They can also promote the proliferation and differentiation of T helper (Th0) cells into Th1 and Th2 cells, activate macrophages and B cells, and produce a variety of cellular factors through activation of p38/MAPK phosphorylation and increased production of NF-κB11. Examples of FIPs with immunomodulatory activity include FIP-fve from Flammulina velutipes and LZ-8 from Ganoderma lucidum (see Table 412). • Terpenes and Terpenoids: Terpenes are hydrocarbons biosynthetically derived from isopentenyl pyrophosphate units, while terpenoids are terpenes with oxygen-containing functional groups. Terpenes and terpenoids from various medicinal mushrooms have shown immunoregulatory activities. For example, Ganoderma species are known for their high content of triterpenoids, which have shown strong immunomodulatory and anti-infective activities. Studies have indicated that terpenes and terpenoids modulate immune system functions by stimulating the expression of genes encoding proteins in the nuclear factor (NF)–κB pathway and mitogen-activated protein kinases. Several terpenoids isolated from Ganoderma lucidum and Ganoderma lingzhi , such as ganoderic acids, have demonstrated immunomodulatory, antitumor, and/or anti-infective activities. However, their mechanisms of action and structure-activity relationships are still poorly understood. It is important to note that the distribution of these compounds varies among fungal species, and their immunomodulatory activities depend on their basic structures and chemical modifications of the fraction composition. Furthermore, different extractions of the same fungus may exhibit non-overlapping but complementary activities. How are immunomodulators classified in clinical practice? In clinical practice, immunomodulators are usually classified into three categories: immunosuppressants, immunostimulants, and immunoadjuvants. • Immunosuppressants are used to suppress the immune response. • Immunostimulants are used to stimulate or enhance the function of the immune system. • Immunoadjuvants are substances that increase the immune response to an antigen, often used in combination with vaccines. The market share of these immunomodulators has increased rapidly in recent years due to their broad medical applications for patients requiring immune system modulation. Immune system modulators are also commonly used as prophylactic medicine for a growing number of healthy people.1 Although most immunomodulators are synthetic or semi-synthetic compounds, there is growing interest in natural immunomodulators, such as those derived from medicinal mushrooms. What mechanisms mediate the immunomodulatory effects of mushrooms? The mechanisms mediating the immunomodulatory effects of mushrooms are diverse and depend on the specific categories of bioactive compounds present. The main ways in which mushrooms exert their immunomodulatory action involve both the innate and adaptive immune systems. In general, bioactive compounds in mushrooms can activate components of the innate immune system such as natural killer (NK) cells, neutrophils, and macrophages, and stimulate the expression and secretion of cytokines. These cytokines, in turn, activate adaptive immunity by promoting the proliferation and differentiation of B cells for antibody production and by stimulating the differentiation of T cells into T helper (Th) 1 and Th2 cells, which mediate cellular and humoral immunity, respectively. Here are the main mechanisms associated with the different categories of bioactive compounds in mushrooms: • Polysaccharides: Polysaccharides are among the most common natural immunomodulators extracted from mushrooms. Their mechanisms of action may include binding to cellular receptors. For example, a glucuronoxylomannan (TAP-3) obtained from Naematelia aurantialba (syn. Tremella aurantialba ) has been shown to promote the secretion of NO, IL-1β, and TNF-α from macrophages. 2 Similarly, a polysaccharide (CCP) from Craterellus cornucopioides enhances the phagocytic function of macrophages and increases cytokine expression through activation of the TLR4–NFκB pathway. 2 In general, high-molecular-weight polysaccharides tend to exhibit greater bioactivity and act by binding to cellular receptors, while low-molecular-weight polysaccharides can penetrate immune cells and exert stimulatory effects from within. The structure of polysaccharides, particularly the presence of a 1,3-β-D-glucan backbone with short 1,6-β-linked branches, is often associated with immunomodulatory activity. Some β-D-glucans, such as lentinan, schizophyllan, and PSK, adopt a triple-helical conformation, which is important for their cytokine-stimulating activity. Chemical modifications such as sulfation can also enhance the immunomodulatory activity of fungal polysaccharides. • Lectins: Fungal lectins mediate their immunomodulatory effects through recognition and interaction with various carbohydrates/glycoproteins on the cell surface. This interaction can lead to several immune responses, including stimulation of nitrite production, increased expression of TNF-α and interleukins, activation of lymphocytes, and promotion of the production of macrophage-activating factors. For example, two lectins extracted from Leucocalocybe mongolica (syn. Tricholoma mongolicum ), TML-1 and TML-2, stimulate the production of nitrite and TNF-α. The lectin from Clitocybe nebularis (CNL) induces the maturation and activation of dendritic cells (DCs) and stimulates several proinflammatory cytokines such as IL-6, IL-8, and TNF-α. • Fungal Immunomodulatory Proteins (FIPs): FIPs exert their immunomodulatory effects primarily through binding to Toll-like receptors (TLRs)10. This binding stimulates antigen-presenting cells and leads to the release of cytokines such as NO and IL-1210. FIPs can also activate p38/MAPK phosphorylation and increase NF-κB production, thereby promoting the proliferation and differentiation of T helper (Th0) cells into Th1 and Th2 cells, activating macrophages and B cells, and producing a variety of cellular factors (see Figure 5)10. For example, FIP-fve from Flammulina velutipes can increase the expression of intercellular adhesion molecules on the surface of T cells through p38/MAPK phosphorylation and activate Th1 cells to produce IL-2 and IFN-γ10. FIP-gts from Ganoderma tsugae can stimulate human peripheral blood monocytes to produce IFN-γ and activates the PI3K/Akt10 signaling pathway. • Terpenes and Terpenoids: Although the mechanisms of action and structure-activity relationships of terpenes and terpenoids are still poorly understood, they have been suggested to modulate immune system function by stimulating the expression of genes encoding proteins in the nuclear factor (NF)–κB pathway and mitogen-activated protein kinases. Triterpenoids from Ganoderma species have shown immunomodulatory and anti-infective activities. In summary, the immunomodulatory effects of medicinal mushrooms are mediated by a complex interplay of diverse bioactive compounds that affect various components and pathways of the innate and adaptive immune system. Polysaccharides often interact with cell-surface receptors and activate intracellular signaling pathways; lectins recognize specific glycosylated structures and can trigger various immune responses; FIPs bind to TLRs, initiating signaling cascades that lead to cytokine production and immune cell activation; and terpenes/terpenoids appear to influence gene expression involved in the immune response. https://pmc.ncbi.nlm.nih.gov/articles/PMC7712035/ Edible and medicinal mushrooms have been used for centuries in various cultures for their nutritional and therapeutic properties. Recently, scientific attention has focused on their immunomodulatory effects , that is, their ability to modulate and enhance the immune system's response. Bioactive Compounds in Mushrooms Mushrooms are rich in bioactive compounds that contribute to their immunomodulatory properties: Polysaccharides , especially β-glucans : These polysaccharides are known for their ability to modulate the immune system. Mushroom β-glucans have a structure characterized by β-1,3-glucan main chains with β-1,6 branches, which are recognized by immune cell receptors, giving them specific immunomodulatory properties. PMC Fungal immunomodulatory proteins (FIPs) : These proteins influence the activity of immune cells, modulating the immune response. Terpenes and terpenoids : Compounds that modulate the immune system by stimulating the expression of genes involved in the immune response, as well as having anti-inflammatory, antioxidant, and antitumor properties. PMC Lectins : proteins that bind specifically to certain sugars, influencing cellular interactions and modulating immune activity. Mechanisms of Action Fungal β-glucans interact with specific receptors on immune cells, such as Dectin-1 , CR3 , and TLR-2/6 , activating macrophages, neutrophils, monocytes, NK cells, and dendritic cells. This interaction modulates both the innate and adaptive immune responses, enhancing phagocytosis and cytokine production. BioMed Central Clinical Efficacy and Scientific Studies Numerous studies have explored the clinical efficacy of medicinal mushrooms: Ganoderma lucidum (Reishi) : Rich in terpenoids, it modulates the immune system by stimulating the expression of genes involved in the immune response and has anti-inflammatory and anti-tumor properties. PMC Trametes versicolor (Turkey Tail) : Used as a non-specific immune modulator, it has shown in clinical studies the ability to improve immune function in cancer patients. Lentinula edodes (Shiitake) : contains β-glucans which stimulate phagocytosis and enhance the innate immune response. Additionally, mushroom extracts such as Maitake have been studied for their potential anti-tumor and immune-boosting properties. Final Considerations Incorporating edible and medicinal mushrooms into the diet or as supplements can offer significant immunomodulatory benefits. However, it is essential to consult a healthcare professional before starting any supplement regimen, especially for individuals with pre-existing medical conditions or taking other medications. Further research is needed to fully understand the mechanisms of action and optimize the therapeutic use of medicinal mushrooms. https://jhoonline.biomedcentral.com/articles/10.1186/1756-8722-2-25 https://pmc.ncbi.nlm.nih.gov/articles/PMC7826851/ https://pmc.ncbi.nlm.nih.gov/articles/PMC8623785

In recent years, research on the gut microbiota has highlighted two key players in human health: the bacterial phyla Bacteroidetes and Firmicutes. Their balance is associated with a state of well-being, while imbalances in their proportion are linked to obesity, inflammation, diabetes, and other chronic conditions. The polysaccharides in medicinal mushrooms are proving to be natural and powerful tools for regulating this balance. Let's see how. The balance between Bacteroidetes and Firmicutes In a healthy microbiota, Bacteroidetes and Firmicutes make up about 90% of the gut bacterial flora. Bacteroidetes are associated with fiber fermentation and the production of short-chain fatty acids (SCFAs), while Firmicutes are linked to greater efficiency in energy absorption. An imbalanced ratio favoring Firmicutes has been connected to obesity and dysbiosis. The role of fungi: documented effects Numerous studies have shown that fungal polysaccharides can influence this ratio: Inonotus obliquus (Chaga): increases Bacteroidetes and reduces Firmicutes in chronic pancreatitis models. Ganoderma lucidum (Reishi): increases the Bacteroidetes/Firmicutes ratio in models of colitis and hyperlipidemia. Auricularia auricular: promotes the growth of Bacteroidetes, particularly the Porphyromonadaceae family. Grifola frondosa (Maitake): stimulates beneficial genera such as Alistipes, Prevotella, and Bacteroides. Agaricus bisporus: in animal models, it increases the relative abundance of Bacteroidetes. An effect that depends on the context Not all fungal polysaccharides act in the same way. Some, such as those from Pleurotus eryngii and Morchella esculenta, have shown a decrease in Bacteroidetes in certain contexts. This highlights the importance of tailoring the intervention by selecting fungal species based on the host's specific conditions. Practical and Therapeutic Implications Modulating the Bacteroidetes/Firmicutes ratio through medicinal mushrooms means: Counteracting intestinal dysbiosis Promote weight loss (in cases of obesity) Improve insulin sensitivity Reduce chronic inflammation Promote the production of SCFAs (butyric, acetic, propionic acid) Smart supplements for a balanced microbiota Supplements containing selected polysaccharides from medicinal mushrooms can help rebalance the bacterial profile of the gut. Depending on the extract, they can promote Bacteroidetes or reduce Firmicutes, restoring the intestinal ecosystem to a composition more favorable to health. Targeted formulations that include extracts of Ganoderma, Inonotus, Auricularia, or Grifola offer a natural, yet scientifically validated, approach to supporting intestinal well-being. Conclusion The mindful use of medicinal mushrooms is a smart strategy to support the balance between Bacteroidetes and Firmicutes. This balance is the foundation for a healthy microbiota, efficient metabolism, and a well-regulated immune system. When choosing your supplements, also think about your microbiota: small organisms, big effects. Discover our products Do you want to help your gut regain balance and well-being? Go to the shop Discover our medicinal mushroom formulations designed to improve microbiota health and restore balance to your gut flora.

In the world of gut health, a new frontier is steadily gaining ground: medicinal mushrooms. Used for centuries in traditional medicine, they are now being rediscovered as valuable allies of the gut microbiota, thanks to a key component: fungal polysaccharides. The gut microbiota: the ecosystem within us The gut microbiota is a microscopic universe made up of trillions of microorganisms, mainly bacteria, that coexist in our intestines. This ecosystem plays a crucial role in maintaining health: it regulates metabolism, modulates the immune system, protects the intestinal barrier, and even communicates with the brain through the gut-brain axis. However, factors such as an unbalanced diet, stress, antibiotics, and pollution can disrupt this balance, leading to dysbiosis and paving the way for intestinal, metabolic, inflammatory, and neurological disorders. Fungal polysaccharides: fuel for the gut flora Fungal polysaccharides are complex carbohydrates that human enzymes cannot digest. This means they reach the colon intact, where they serve as ideal nourishment for the beneficial bacteria in the microbiota. Specifically, they stimulate the growth of probiotic species such as Bifidobacterium and Lactobacillus, thus acting as true natural prebiotics. Once fermented by gut microbes, these polysaccharides are transformed into bioactive metabolites, particularly short-chain fatty acids (SCFAs) such as acetic, propionic, and butyric acid. These molecules not only nourish colon cells but also help strengthen the intestinal barrier, reduce inflammation, and regulate blood sugar and lipid metabolism. Structure is everything: composition and function Not all fungal polysaccharides are the same. Their effectiveness depends on several factors: Molecular weight: Polysaccharides with different weights show varying activity in modulating the microbiota. Monosaccharide composition: Polysaccharides can be glucans (composed only of glucose) or heteropolysaccharides (made up of multiple sugars, such as mannose, galactose, xylose, fucose, etc.). Type of glycosidic bonds: The arrangement of bonds is fundamental. For example, the (1→3)-β-glucans of Lentinula edodes have been shown to increase beneficial bacterial species such as Clostridiales, Lachnospiraceae, and Ruminococcaceae. An emblematic example is the polysaccharide from the fungus Flammulina velutipes, composed of five types of sugars, which has promoted the proliferation of entire families of bacteria beneficial to gut health. From polysaccharides to tangible benefits What does all this mean for the guest's health? More energy for the colon: The SCFAs produced by fermentation provide direct fuel to the intestinal cells. Stronger intestinal barrier: SCFAs like butyrate strengthen the tight junctions between epithelial cells, reducing intestinal permeability (leaky gut). Immune system regulation: Polysaccharides modulate local and systemic immune responses, helping to prevent chronic inflammation. Positive effect on metabolism: They support blood sugar regulation, weight management, and liver health. The added value of supplements In light of these discoveries, medicinal mushrooms are no longer just a traditional remedy but an advanced component of modern nutraceuticals. Supplements based on mushrooms such as Ganoderma lucidum, Hericium erinaceus, Auricularia auricula o Grifola frondosa They can provide a natural yet scientifically supported aid for intestinal well-being. For companies committed to natural health, formulating products containing fungal polysaccharides means offering their customers effective, safe, and sustainable solutions to rebalance gut flora and enhance overall health. Conclusion The symbiosis between medicinal mushrooms and the gut microbiota opens new horizons for overall well-being. Thanks to their polysaccharides, mushrooms act as true architects of the microbiota, selectively and beneficially modulating the intestinal flora. Including them in your diet or daily supplements is a simple yet powerfully transformative step for those who want to take care of their health starting from the gut. Discover our products Do you want to discover how our medicinal mushroom supplements can help you regain balance and intestinal wellness? Go to the shop You will find a selection of products formulated with the highest quality extracts, designed to support your health naturally and safely.