The degradation of EMPs in the colon is facilitated by a group of enzymes known as carbohydrate-active enzymes (CAZymes) (54). While the human genome encodes only 8–17 GH enzymes with limited capability to digest complex carbohydrates, more than 10,000 CAZymes that can break down complex carbohydrates have been identified in 177 reference bacterial genomes (55). This indicates that the gut microbiota is responsible for the degradation of various polysaccharides, including β-glucans, into monosaccharides or oligosaccharides, which can modulate the intestinal microbiota and promote the growth of probiotics (56, 57). Numerous studies have shown that most EMPs are fermented by the intestinal microbiota, resulting in the generation of short-chain fatty acids (SCFAs) and alteration of the microbiota composition (Table 3). For instance, after simulated digestion, the Pleurotus eryngii polysaccharide (PEP) remained structurally intact with maintained molecular weight and was effectively utilized and broken down by the intestinal microbiota through fermentation, leading to the production of various SCFAs (62). Conversely, the molecular weight of Oudemansiella radicata polysaccharides (ORP) decreased during simulated digestion, but its overall structure remained intact. Additionally, no free monosaccharides were detected, implying that ORP is indigestible (64).

EMPs, which are difficult to digest and absorb, can function as a carbon source for the intestinal microbiota. This, in turn, can enhance human intestinal health and preserve physiological activity by promoting diversity and regulating the composition of gut microbiota. Research has demonstrated that the protective effects of EMPs on intestinal microbiota regulation are diverse. In terms of gut microbiota composition, The intake of EMPs can stimulate the growth of beneficial bacteria while suppressing the harmful ones, which contributes to a more balanced microbiota composition (68). In terms of gut microbiota function, EMPs can enhance CAZymes activity, increase SCFAs production, reduce proinflammatory factor expression, and boost tight junction protein expression, thereby promoting the overall intestinal health of the organism (69). In vitro fermentation studies have shown that Pleurotus eryngii polysaccharide (PEP) altered gut microbiota composition by boosting Firmicutes and reducing Proteobacteria and Bacteroidetes (62). Tremella fuciformi polysaccharide was found to be significantly consumed by the colonic microbiota in human feces, stimulating the growth of Phascolarctobacterium, Bacteroides, and Lachnoclostridium (61). Meanwhile, Cyclocybe cylindracea, Pleurotus eryngii, and Pleurotus ostreatus polysaccharides positively impacted gut microbiota composition, increasing populations of F. prausnitzii and Bifidobacteriumspp (70). Flammulina velutipes polysaccharides elevated the Bacteroidetes to Firmicutes ratio and fostered the growth of beneficial gut microbiota, particularly Bifidobacterium and Bacteroides (71). Although in vitro studies are confined to specific types of gut microbiota bacteria, it is noteworthy that EMPs have a considerable influence on the diversity, richness, and overall composition of the gut microbiota. Additionally, EMPs from various sources have different impacts on gut microbiota modulation, which could be due to structural variations in the EMPs (72, 73).

Besides, research from both animal models and clinical trials has shown that the consumption of EMPs can modify the composition of the gut microbiota. Animal studies have demonstrated that Agrocybe cylindracea Polysaccharides can favorably modify the gut microbiota and related metabolites, reducing levels of Desulfovibrio and increasing abundance of Parabacteroides to prevent diet-induced obesity in mice (74). Tremella fuciformis polysaccharide (TPs) can substantially increase the diversity of the gut microbiota and restore the relative abundance of certain bacterial species, such as Odoribacter, Lactobacillus, Marinifilaceae, and Ruminococcaceae. This finding suggests that TPs may exert a protective effect on dextran sulfate sodium (DSS)-induced colitis in mice (75). Furthermore, in a clinical trial, a β-D-glucan-enriched extract derived from Lentinula edodes was found to raise the relative abundance of Ruminococcaceae UCG-014, Erysipelotrichaceae UCG-003, Akkermansia, and Subdoligranulum, thereby influencing lipid metabolism (76).

In summary, the supplementation of EMPs can alter the composition of the gut microbiota, enhance diversity and richness, and raise the abundance of various species, all of which have important health implications. Additionally, EMPs can restrict the growth of harmful microorganisms. There are several reasons behind these effects. Firstly, gut microbiota ferment EMPs into short-chain fatty acids (SCFAs) as end-products, which lower the intestinal pH and provide a more favorable environment for the growth of beneficial bacteria (66, 76). For instance, Firmicutes are more tolerant to weakly acidic environments than Bacteroidetes (77). Microorganisms specializing in polysaccharide degradation become dominant by breaking down polysaccharides (78). Moreover, some microorganisms can use the metabolites produced during the degradation of EMPs by other microorganisms as a carbon and energy source to promote their growth (79). For example, multi-species symbiotic cross-feeding can occur between Enterobacteriaceae and Bacteroidales spp., leading to synergistic development of mixed communities in vitro (80). Ruminococcus bromii can produce fermentation products by fermenting resistant starch to support the growth of other symbiotic bacteria (81). Overall, while it is evident that EMPs play a role in regulating gut microecology, the precise mechanisms by which they affect microbial growth and the pathways involved are still unclear and require further investigation. In addition, mushrooms may be a source of toxic heavy metals that may have adverse health effects (82). For example, the report on heavy metal concentrations in wild edible mushrooms in Yunnan Province (China) showed that heavy metal contamination in wild edible mushrooms is a serious problem (83). More studies are recommended to elucidate possible procedures for the accumulation of toxic heavy metals in edible mushrooms.

The gut microbiota can produce energy for its growth through the fermentation of EMPs. This process generates a mixture of gases, including CO₂, methane, and hydrogen, as well as short-chain fatty acids (SCFAs) such as acetic, propionate, and butyrate. Studies have demonstrated that SCFAs can reach other tissues and organs through the circulatory system, contributing to various health-promoting effects. These molecules modulate the intestinal immune system to maintain homeostasis and regulate the production of hormones such as Glucagon Peptide 1 (GLP-1) and insulin, through their interactions with L-endocrine cells and small intestine endothelial cells (84). SCFAs also activate G-protein-coupled receptor (GPCR) signaling pathways, inducing the transcription of factors such as hypoxia-inducible factor 1 (HIF-1), signal transducer and activator of transcription 3 (STAT3), and specificity protein 1 (SP1), thereby enhancing epithelial barrier function, boosting the production of antimicrobial peptides, and reducing inflammation (85). Furthermore, they reduce the activity of histone acetyltransferases and histone deacetylases, which control gene expression, and prevent the maturation of monocytes into dendritic cells and macrophages, along with their production of inflammatory cytokines (86). SCFAs have also been shown to act as ligands for the free fatty acid receptor (FFAR), influencing the host's immunological activity (87). Therefore, SCFAs have a broad range of effects on host metabolism, proliferation, and differentiation, serving as signaling molecules.

Studies have shown that SCFAs are the primary byproducts of gut microbiota fermentation of EMPs and play a critical role in maintaining overall health. For instance, polysaccharides derived from Flammulina velutipes have been shown to increase the levels of acetic acid, propionic acid, and butyric acid, which can enhance the immunity of immunocompromised mice (88). The polysaccharides from Ganoderma lucidum have also been observed to increase the concentration of SCFAs in human gastrointestinal simulations, specifically acetic acid, propionic acid, and n-butyrate (89). Furthermore, polysaccharides from Sparassis crispa have been found to regulate blood sugar levels through modulation of SCFAs concentration (90). Therefore, the health benefits of EMPs can be attributed to the type and amount of SCFAs produced in the gut.

The structural features of EMPs have significant impacts on their biological activities and their regulatory effects on the gut microbiota (Table 4). Specifically, the molecular weight of EMPs can affect their absorption and metabolism in the gut. Research has shown that EMPs with lower molecular weights are more readily metabolized by gut microbiota, leading to higher production of short-chain fatty acids (SCFAs), such as propionate, butyrate, and acetate, while EMPs with higher molecular weights are less readily metabolized, resulting in lower SCFA production (108–110). For example, low molecular weight polysaccharides (<10 kDa) from Ganoderma lucidum have better fermentation and higher gas production ability, stimulating the growth of intestinal bacteria quickly. On the other hand, high molecular weight polysaccharides (>100 kDa) are more difficult to be fermented by intestinal bacteria and have a longer residence time in the intestines, resulting in a more prolonged effect on the intestinal microbiota (110). Furthermore, the monosaccharide composition of EMPs also plays a crucial role in regulating the gut microbiota. For instance, glucose, xylose, and galactose are among the most common monosaccharides found in EMPs, with glucose being one of the most prevalent. Glucose has been found to promote the growth and metabolism of gut microbiota, thereby maintaining gut health (79). Research has indicated that glucose can stimulate the metabolic activity of gut microbiota, increase the growth of beneficial bacteria, and promote the production of metabolites, thereby enhancing the immune function of the gut and protecting the gut mucosa (111). Although xylose and galactose are present in relatively low amounts in EMPs, their effects on the gut microbiota cannot be ignored. Xylose can promote the growth of probiotics and protect the gut mucosa by increasing the production of beneficial metabolites (112). Galactose, on the other hand, can inhibit the growth of harmful bacteria, reducing the production of harmful metabolites and benefiting gut health (113). For example, A polysaccharide from Pleurotus eryngii, rich in glucose (78.32%), galactose (8.47%), and mannose (9.43%), promoted the relative abundance of Firmicutes and reduced that of Bacteroidetes and Proteobacteria, while increasing the production of acetic and propionic acids (62). A polysaccharide from Hericium erinaceus, composed of fructose, mannose, glucose and galactose, enhanced the abundance of SCFA-producing bacteria (58). In addition, the length and branching patterns of EMPs can also affect their degradation and absorption in the gut (2). Studies have indicated that shorter chain lengths and fewer branching patterns can enhance the absorption and utilization of EMPs in the gut, resulting in better regulatory effects (18). Additionally, the length and branching patterns of EMPs can also influence their metabolites in the gut, which in turn affect the growth and metabolism of gut microbiota (114). Zhang et al. obtained Sparassis crispa polysaccharides with main chain structures of (1 → 6)-α-D-Galp, (1 → 6)-β-D-Glcp and (1 → 3)-β-D-Glcp and side chain structures of (1 → 4)-β-D-Glcp, (1 → 3)-β-D-Glcp, T-α-L-Fucp and T-β-D-Glcp can promote the production of short-chain fatty acids and the abundance of probiotics, such as Dialister and Megasphaera (63, 98). Therefore, in order to fully realize the regulatory effects of EMPs, further research is needed to explore the relationships between their structural features and gut microbiota metabolism, as well as the impacts of different mushroom species and polysaccharide sources on their regulatory effects. This will provide a more robust scientific basis for the application of EMPs.

Metabolic diseases encompass a range of conditions affecting the metabolism of the human body. Research on metabolic syndrome populations and animal models has revealed that gut ecological dysbiosis often results in a decrease in the abundance of probiotics, an increase in opportunistic and pathogenic bacteria, and a reduction in microbial diversity (135). Imbalances in the intestinal ecosystem can cause a reduction in the expression of tight junction proteins in the intestine, resulting in an increase of intestinal permeability, impaired intestinal integrity, and the release of bacterial debris and endotoxins from the gut into the bloodstream. This triggers the activation of the NF-κB and NLRP3 signaling pathways in inflammatory vesicles, resulting in elevated levels of pro-inflammatory factors such as IL-1, IL-6, and TNF-α, ultimately leading to chronic low-grade inflammation throughout the body (136). Additionally, activation of the NF-κB signaling pathway increases the levels of protein phosphatase 1B (PTP1B), which dephosphorylates the insulin receptor or its substrate, hindering the insulin receptor's ability to bind with insulin, and causing insulin resistance (137). Dysbiosis in the intestinal tract also impairs the synthesis of vitamins K and B, folic acid, neurotransmitters, SCFAs, and other bioactive components by gut microbes (138). Therefore, imbalances in the gut microbiota are a key contributor to the onset and expression of metabolic disorders.

Studies have indicated that the consumption of EMPs has a positive impact on metabolic disorders. In animal models, such as dietary-induced obese mice, a polysaccharide from Ganoderma lucidum (BSGLP) containing (1 → 3)-β-D-Glcp, (1 → 3,6)-β-D-Glcp, (1 → 6)-β-D-Glcp, and terminal-β-D-Glcp moieties has been demonstrated to restore balance to the gut microbiota and mitigate dysbiosis, leading to a reduction in fat accumulation and a decrease in inflammation (69). Similar results have been observed with Dictyophora indusiata polysaccharides consisting of glucose 59.84%, mannose 23.55% and galactose 12.95% which mitigated hepatic steatosis, hyperlipidemia, hyperglycemia, and LPS-induced inflammation in mice with high-fat diet-induced obesity (DIO) by reducing the abundance of Bacilli, Gammaproteobacteria, and increasing abundance of Bacteroidiaas (139). Supplementation with Cordyceps militaris Polysaccharides containing 1, 3-branched-galactomannoglucan with a linear backbone of (1 → 4)-linked α-D-Glcp in mice on a high-fat diet led to reduced body weight, pro-inflammatory cytokine levels, and fat accumulation, as well as improved glucose tolerance and intestinal barrier function. This was shown to be a result of reversing intestinal dysbiosis, as evidenced by an increased population of Alloprevotella, Butyricimonas, Parabacteroides, and Alistipes (122). Supplementation with Ganoderma lucidum polysaccharides consisting of arabinose, galactose, glucose, xylose, mannose, ribose, and rhamnose with molar percentages of 5.32%, 5.47%, 57.63%, 0.84%, 25.41%, 1.95%, and 3.38%, respectively, and molecular weight of 15900 Da improved insulin secretion and repaired islet cells, stimulated glycogen synthesis and storage in the liver, and enhanced antioxidant enzyme activities and insulin sensitivity in diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ) by elevating the abundance of Lactobacillus, Bacteroides, and Ruminococcaceae (130). The polysaccharide from Ganoderma lucidum with a molecular weight of 13.7 kDa, mannose, glucose, galactose, rhamnose, and arabinose in a molar ratio of 3.16:16.17:3.74:1.65:1 effectively reduced fasting blood glucose and insulin levels and improved gut microbiome imbalances by decreasing the levels of Aerococcus, Corynebacterium, Proteus, and Ruminococcus (140). Polysaccharide extracted from Phellinus linteus with the backbone of → 3)-β-d-Glcp-(1 → and → 6)-β-d-Glcp-(1 → has been shown to effectively reduce fasting blood glucose levels in mice. This is achieved by altering liver phospholipid metabolism and improving insulin signaling, as well as increasing the abundance of Porphyromonas (141). In general, EMPs have the potential to regulate gut microbiota by promoting the growth of beneficial bacteria and inhibiting that of harmful bacteria, which could improve gut health and prevent or treat metabolic disorders.

Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease (CD), is marked by persistent inflammation in the gastrointestinal tract (142). Symptoms of IBD include diarrhea, bloating, abdominal pain, blood in stools, weight loss, and discomfort. Research suggests that IBD arises from a genetically susceptible individual's misguided inflammatory response to the gut microbiome (143). The most prevalent imbalance in the intestinal flora among IBD patients is a decrease in Bifidobacterium adolescentis, prausnitzii, Dialister invisus, Faecalibacterium and an unnamed member of Clostridium cluster XIVa, and an increase in Ruminococcus gnavus (144, 145). In addition to intestinal ecological dysbiosis, metabolites derived from gut bacteria, such as short-chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites, also play a crucial role in the development and progression of IBD. The latest extensive and comprehensive study found that gut microbiome metabolites impact host immunity, mucosal health, homeostasis, and energy metabolism (146). As such, the composition and function of the intestinal microbiota are crucial factors that impact the progression of IBD.

Medical treatments for IBD mainly aim to control inflammation and prevent the progression of the disease. There are three main types of conventional drugs that are commonly used in IBD treatment, including aminosalicylic acid derivatives, glucocorticoids, and immunosuppressive drugs (147). However, prolonged use of these drugs can lead to reduced immunity, and increase the risk of electrolyte imbalances, peptic ulcers, cataracts, and osteoporosis (148). Recent studies have shown that EMPs can improve intestinal health with minimal adverse effects. EMPs, as a natural immunomodulator, are effective in treating and preventing IBD by regulating gut bacteria and upregulating the expression of tight junction proteins (TJs), such as junctional adhesion molecules, cytosolic scaffold proteins, occludin, and intracellular zonulae occludens like ZO-1. For instance, high doses of polysaccharides from Tremella fuciformis have the potential to improve gut health by increasing the diversity of the gut microbiome, restoring the relative abundance of specific bacteria such as Helicobacter, Odoribacter, Lactobacillus, Marinifilaceae, and Ruminococcaceae, and activating Foxp3+ T cells to produce anti-inflammatory cytokines. This was observed in mice with colitis induced by dextran sulfate sodium, and the treatment showed minimal side effects (75). A polysaccharide from Flammulina velutipes has been shown to alleviate colitis by controlling colonic microbial dysbiosis, increasing short-chain fatty acids, and inhibiting the TLR4-NF-κB signaling pathway (133). The polysaccharide from Dictyophora indusiata consisting of 59.84% glucose, 23.55% mannose, and 12.95% galactose has been shown to improve gut microbiota composition and intestinal barrier function by increasing the expression of mucins and tight junction proteins, suppressing harmful bacteria such as Gammaproteobacteria, Proteobacteria, Bacteroidaceae, Bacteroides, and Enterobacteriaceae, and enhancing beneficial bacteria such as Lactobacillus acidophilus (149). Polysaccharides isolated from sporoderm-removed fragments of Ganoderma lucidum consisting of arabinose (4.19%), mannose (15.69%), glucose (78.15%), and galactose (1.97%) have been shown to mitigate colitis induced by Azoxymethane/Dextran Sodium Sulfate by improving gut dysbiosis, increasing short-chain fatty acid production, and suppressing TLR4/MyD88/NF-κB signaling to alleviate endotoxemia (134). Yu et al. (150) demonstrated that polysaccharides from Porphyra haitanensis improved the integrity of the colonic mucosal barrier by upregulating tight junction proteins, augmenting the mucus layer and its secretion, and regulating the gut microbial community, enriching beneficial bacteria such as Bacteroides, Muribaculum, and Lactobacillus species, thus mitigating DSS-induced colonic injury. In general, EMPs may alleviate IBD by regulating gut microbiota and repairing the damaged intestinal barrier, creating an environment conducive to the growth of probiotics and suppressing potentially pathogenic bacteria, and modulating TLR4 and NF-κB signaling pathways to reduce intestinal inflammation.

Microbial commensal dysbiosis, responsible for 20% of tumorigenesis and a greater number of cancers, has been linked to microbial pathogens (151). In a healthy gut microbiome, many probiotics and other resident bacteria secrete molecules to fight tumor growth and prevent tumorigenesis. However, when the intestinal flora is dysbiotic, certain bacterial pathogens can grow and proliferate, secreting toxins such as CagA protein from Helicobacter pylori, adhesin A (FadA) from Fusobacterium nucleatum, and metalloproteinase toxin (MP toxin) from Bacteroides fragilis, which interfere with the development of the host cell and eventually lead to the onset of cancer (152). A recent study has shown that lung cancer patients experience a significant shift in gut microbiota composition compared to healthy individuals, with pathogens increasing and some probiotic bacteria decreasing (153). Additionally, certain bacteria can also interfere with the host's hormone metabolism. Intestinal dysbiosis also increases the relative abundance of Clostridium leptum and Clostridium coccoides, leading to increased secretion of bacterial β-glucuronidase enzymes, which promotes cell proliferation in organs such as the endometrium and breast and may contribute to the development of breast cancer (152, 154). During dysbiosis, several microbiota subpopulations may proliferate, producing high quantities of toxins that cause inflammation and cancer.

According to research in vivo and clinical tests, consuming EMPs may be a viable and efficient method for cancer prevention and treatment (155). EMPs can induce the proliferation of beneficial bacteria in the gut, thus increasing the ability to combat carcinogens and reducing the nourishment of harmful bacteria. This reduces the amount of harmful substances in the gut, reducing cellular damage and preventing intestinal cancer. In addition, EMPs have been shown to enhance the immune system's activity, which can lead to the inhibition of cancer cell growth. For instance, A polysaccharide extracted from the mushroom Pleurotus ostreatus has been demonstrated to decrease tumor cell metastasis and increase survival in mice with H22 malignant ascites. This effect was achieved by downregulating the expression of genes such as Stat3 and Foxp3, as well as releasing immunological factors including TNFα, INFγ, and IL-2 (156). Polysaccharides from Ganoderma lucidum have been found to be more effective in alleviating colorectal cancer symptoms than guar gum, as they increase the prevalence of Akkermansia, colon length, and downregulate rectal cancer-related genes (157). Ganoderma lucidum polysaccharides have demonstrated cancer-preventive and therapeutic functions by dynamically modulating the gut microbiota and host immune responses (158). Studies have also shown that sporoderm-broken fragments of (G. lucidum) polysaccharides (BSGLP) were more effective in reducing gastric cancer cell survival than removed fragments of G. lucidum (RSGLP). RSGLP induced apoptosis in AGS cells by dramatically increasing cleaved-PARP and decreasing Bcl-2 and pro-caspase-3 expression levels, while enhancing the expression of LC3-II and p62, indicating autophagy was induced and the autophagic flow was disrupted in AGS cells (159). A recent study discovered that polysaccharides from the Sporoderm-Breaking Spore of Ganoderma lucidum with a molecular weight of 3659 Da can serve as a natural adjuvant in breast cancer treatment, boosting the number of cytotoxic T cells and helper T cells. The gut microbiota is also affected, with increased levels of Firmicutes and Proteobacteria and reduced levels of Actinobacteria, Bacteroidetes, and Cyanobacteria, leading to improved symptoms (160). Additionally, a polysaccharide derived from the spore of Ganoderma lucidum when combined with Paclitaxel can act as an adjuvant against Pertussis toxin in breast cancer treatment. This restores gut microbiota dysbiosis, increasing levels of Ruminococcus and Bacteroides while reducing the presence of cancer-risk genera such as Odoribacter and Desulfovibrio (161). These studies suggest that EMPs can inhibit tumor proliferation by remodeling the gut microbiota, but the anti-tumor effect of EMPs in regulating intestinal microbiota has been only demonstrated in some EMPs.

In-depth research has revealed that EMPs offer a range of health benefits, including prevention of cardiovascular disease, liver protection, and improvement of neurological symptoms. For instance, treatment with Auricularia auricula polysaccharides with monosaccharides composed of glucose (72%), mannose (8%), xylose (10%), and fucose (10%) and containing a pyranose ring has been found to enhance cardiac function due to its potent antioxidant properties (162). Studies have demonstrated that polysaccharides from Agrocybe aegerita composed of arabinose, mannose, Galactose, and glucose display potential anti-aging, antioxidant, and organ-protective effects on the liver, brain, and kidney against D-gal-induced aging toxicity, slowing the aging process (163). The polysaccharide of Hypsizygus ulmarius containing galactose (44.24%), glucose (34.27%), mannose (15.61%) along with the small amount of xylose (3.33%), fucose (1.33%), and rhamnose (1.20%) has been shown to have a significant hepatoprotective effect against acute alcoholic liver damage in rats, as it protects the biological system from oxidative stress (26). Ganoderma lucidum polysaccharides with a molecular weight of 15.0 kDa have been found to reduce cognitive impairments in transgenic Alzheimer's disease (AD) mice by boosting neural progenitor cell proliferation (164). The polysaccharide-peptide complex of Cordyceps militaris consisting of mannose, glucose, and galactose with a molar ratio of 2.0:11.4:1 has been shown to regulate the lncRNA-miRNA-mRNA axis, thereby improving atherosclerosis (165). In conclusion, EMPs possess multiple bioactivities and play a positive role in maintaining bodily health.