Research progress on the mechanism of functional activity of edible fungi polysaccharides—focusing intestinal mucus as a key and entry point

Yun-Yan Yu; Ya-Ning Duan; Sai Ma; Qiu-Hui Hu; Gao-Xing Ma

doi:10.26599/FMH.2025.9420042

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Review Article | Open Access

Research progress on the mechanism of functional activity of edible fungi polysaccharides—focusing intestinal mucus as a key and entry point

Yun-Yan Yu^{^†}, Ya-Ning Duan^{^†}, Sai Ma, Qiu-Hui Hu, Gao-Xing Ma()

Collaborative Innovation Center for Modern Grain Circulation and Safety, Jiangsu Province Engineering Research Center of Edible Fungus Preservation and Intensive Processing, College of Food Science and Engineering, Nanjing University of Finance and Economics, Nanjing 210023, China

^†These authors contributed equally to this work.

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Highlights

(1) The direct and indirect mechanism of immune function of edible fungi polysaccharides.

(2) The function of the intestinal mucus barrier in intestinal immunity.

(3) Mucins and edible fungi polysaccharides engage in electrostatic interactions.

(4) Interaction of polysaccharides with mucins is mediated by intestinal microorganisms.

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Edible fungi polysaccharide is a kind of natural active substance, which plays an important role in immune regulation. The research on the mechanism of polysaccharide activity in the early stage mainly focused on the direct action mechanism between polysaccharide and cell, and the indirect action mechanism between polysaccharide and microbe and cell. It mainly focused on the enhancement of immune cells and the regulation of immune active factors, as well as the regulation of intestinal microenvironment homeostasis. Due to the complexity of the intestinal environment, polysaccharides need to interact with the mucous layer of the intestinal tract before entering the intestinal tract to play the function of immune activity. This interaction will change the structure, viscosity and dispersion of polysaccharides, thus affecting the activity of polysaccharides in the body. Therefore, the interaction between polysaccharide and mucus layer is also extremely important. Edible fungi polysaccharides can supplement mucinoglycan to change the glycosylation level of mucin, and also affect the abundance of mucin symbiotic flora, thus changing the secretion of mucin. As prebiotics, the short-chain fatty acids produced by polysaccharides can not only directly act on intestinal epithelial cells, but also maintain energy generation. It can also stimulate goblet cells and maintain mucus barrier homeostasis. The effect of the interaction between polysaccharide and intestinal mucus on intestinal immune activity can be a new direction to study the mechanism of polysaccharide activity.

Abstract

Edible fungi polysaccharide is a naturally active substance with a complex structure, which has immunomodulatory activity, can regulate intestinal flora, and reduces the body’s inflammatory response. Currently, studies on the immune activity of polysaccharides from edible fungi mainly focus on intestinal immunity. Based on the current research direction on the immune activity mechanism of polysaccharides, this paper summarized the direct effects of polysaccharides on intestinal immune cells and the indirect regulatory effects mediated by intestinal flora. At the same time, we found that the active function of polysaccharides needs to pass through the intestinal mucus layer first. The intestinal mucus layer is rich in mucins and special microorganisms with mucins as the carbon source, which act as the first line of defense of the intestinal barrier. The interaction between polysaccharides and intestinal mucins will affect the integrity of the intestinal barrier. And the interaction between polysaccharides and intestinal mucin, to provide a new strategy for the study of the activity mechanism of edible fungi polysaccharides.

Keywords

edible fungi polysaccharides intestinal immunity mucin intestinal flora

References

[1]

Yang, M. Y., Tarun, B., Hari, P. D., et al. Trends of utilizing mushroom polysaccharides (MPs) as potent nutraceutical components in food and medicine: a comprehensive review. Trends in Food Science & Technology, 2019, 92: 94–110. https://doi.org/10.1016/j.jpgs.2019.08.009

Function	Source	Name	Molecular weight (Da)	Monosaccharide composition	Model	Mechanism	Reference
The activation of immune response signaling pathways in immune cells, inducing their secretion of immune factors	P. eryngii	EPA-1	9.97 × 10⁴	Man, Glu and Gal (2.2:1.0:3.2)	RAW 264.7 cell	Release the immune activity factor of NO, TNF-α, IL-1 and IL-6 through activation of signal protein of P38, ERK, JNK in MAPKs and translocation of nuclear NF-κΒ	[15]
	F. velutipes	FVPB1	2.04 × 10⁴	Gal, Man, Fuc and Glu (1.8:1.2:1:15.4)	B cell	Stimulate B cells, promote B cell proliferation, and increase secretion of IgG, IgM and IL-10 by B cells, activating Breg to release IL-10 via JNK, P38 and ERK1/2 signaling pathways	[16]
	Morchella esculenta	SFMP-1, CFMP-1	7.0 × 10³, 6.9 × 10³	Nm	NR8383 cell	Suppress nuclear translation of the NF-κB and inhibit the degradation and phosphorylation of NF-κB	[17]
	Astragalus	APS	Nm	Nm	IEC-6 cell	Inhibit the expression of TNF-α and IL-8 mRNA, and decrease the activity of NF-κB protein	[18]
Regulation of the oxidative stress damage signaling pathway	Sarcodon imbricatus	SIPS	56 331.8−93 963.6	Nm	BALB/c mice	Regulate the production of immunoglobulins including IgA, IgG and IgM in the serum and spleen, promote the secretion of IL-2, IL-6, IL-10, IL-12 and IFN-γ of serum and spleen in CTX-induced immunosuppressive mice	[19]
	G. atrum	PSG-1	Nm	Man, Gal and Glu	CTX-induced immune dysfunction in mice	Increase the activities of the antioxidant enzymes (SOD, CAT and GPx) in spleen and thymus of the mice subjected to CTX	[20]
	G. lucidum	GAP	Nm	Nm	IEC-6 cell	Decrease LDH activity and MDA content, and increase SOD and GSH-Px activities	[21]
	Dictyophora indusiata	DIP	Nm	Nm	RAW 264.7 cell	Activate MAPK and NF-κB signaling pathway, and stimulate macrophages to secrete NO, IL-1β, IL-6, TNF-α and other inflammatory cytokines	[24]
Combined with cell membrane-specific pattern recognition receptors, such as β-glucan receptors, Dectin-1 receptors, Toll-like receptors, etc., stimulating immune cells to exert immune-enhancing effects	I. obliquus	EE (16.2%), PEF (0.24%), EAF (2%), n-BF (3.92%) and WF (9.6%)	Nm	Nm	RAW 264.7 cell	Inhibit effects on NO production and NF-κB luciferase activity in macrophage RAW 264.7 cells and cytotoxicity against human prostatic carcinoma cell PC3 and breast carcinoma cell MDA-MB-231	[22]
	G. lucidum G0119, G0154 and their hybrid strain GZ36	G0119-P1, G0119-P3 G0154-P1, G0154-P2, G0154-P3 GZ36-P1, GZ36-P3	5.193 × 10⁶, 6.033 × 10⁴, 8.957 × 10⁶, 4.437 × 10⁶, 6.184 × 10⁴, 7.549 × 10⁶, 8.148 × 10⁴	Gul, Xyl, Man, Gal and Fuc	RAW 264.7 cell HEK-Blue^TM hDectin-1 a cell	The 20 E of the three strains (G0119, G0154 and GZ36) stimulates Dectin-1	[23]
	P. eryngii, L. edodes, Coprinus comatu, Hericium erinaceus, Ganoderma lingzhi	PE, LE, CC, HE, GLLZ-2, GLHN-1	4.826 × 10⁶, 3.538 × 10⁶, 1.272 × 10⁷, 3.213 × 10⁶, 1.850 × 10⁶, 3.240 × 10⁶	Fuc, Glu, Gal, Xyl, Man	HEK-Blue^TM hDectin-1 a cell	Ganoderma lucidum and hericium 30E with higher β-glucan content had stronger activity to activate Dectin-1 receptor in vitro	[25]

Function	Source	Name	Molecular weight (Da)	Monosaccharide Composition	Model	Mechanism	Reference
Fermented by the intestinal flora colonising the colon as a source of energy after ingestion and converted into other active components such as SCFAs, thus exerting the corresponding intestinal immune-enhancing functional activities	P. ostreatus	POPS-1, POPS-2, POPS-3	Nm	Nm	A. japonicus	The relative abundance of Proteobacteria was reduced, while the relative abundance of Chloroflexi was increased	[30]
	H. erinaceus	HECP	8.667 × 10⁴	Nm	DSS-induced colitis in C57BL/6 mice	Modulate the distribution of the intestinal flora, restore the relative abundances of vital bacteria including Clostridiales, Akkermansia and Desulfovibrio, prevent the imbalance of gut microbiota	[31]
	T. fuciformis	HTP	Nm	Nm	DSS-induced colitis in mice	Increase gut community diversity, and restore the relative abundances of Lactobacillus, Odoribacter, Helicobacter, Ruminococcaceae, and Marinifilaceae	[33]
	G. lucidum	GLP	1.37 × 10⁴	Man, Glu, Gal, Rha and Ara (3.16:16.17:3.74:1.65:1)	HFD and streptozotocin-induced type 2 diabetic rats	Inhibited inflammatory substances metabolism, reduce fasting blood glucose and insulin levels	[34]
	Wild morels	MP	Nm	Nm	Cyclophosphamide (Cy)-treated mice	Increase levels of SCFA-producing bacteria	[36]
	Pleurotus geesteranus	PGP	4.87 × 10⁶, 9.84 × 10⁶	Glu, Gal	ALD mice	Affect the α- and β- diversity of gut microbiota, alter the gut microbial community at the phylum and genus levels	[37]

Source	Name	Model	Dosages and time	Effect on mucin	Effect on intestinal flora	Protein/mRNA expression	Mechanism	Reference
Hericium	HFP	Forskolin, a cAMP agonist (FSK)-induced ICR mice model	100, 200, 400 mg/(kg∙day) for 14 days	Improve the coverage of mucus in both mouse ileum and colon Not upregulate the expression of MUC2 gene	Ruminococcaceae↑ Lachnospiraceae↑ Staphylococcus↓ Enterobacter↓	ANO1↑ (activating chloride channel expression) f5-HT and PGE2↑	HFP modulates intestinal microbiota and gut fluid secretion through targeting chloride channels CFTR and CaCCs	[66]
F. velutipes	FVP	CdCl₂ induced intestinal -intestinal injury model. Pseudo-sterile mice treated with antibiotics. Fecal microbial transplantation	100 mg/kg b.w., gavage for 4 weeks	Cannot form FVP-mucin layer, FVP moleculesmight enter and go through the intestinal mucin layer to reach and interact with intestinal epithelium to secrete mucus and provide additional	Bacteroides↑ Desulfovibrionales↓ Clostridium↓	Occludin and Claudin-1↑ GPR43 and GPR109A↑	As an effective therapeutic agent against CdCl₂-induced gut damage via SCFA-mediated regulation of intestinal inflammation and gut microbiota-related energy metabolism	[67]
B. aereus ameliorates	BAP	DSS-induced colitis C57BL mice model	200, 400 mg/kg for 14 days	BAP1-1 intervention improved the defect in the number of MUC2-positive goblet cells in colitis mice and promoted the activation of MANF	Lachnospireaceae -NK4A136↑ Prevotellaceae↑ Bacteroidaceae↑	Tff3, Muc2 and Klf4↑ key glycosyltransferase (Chst4, Fut2, and Gal3st2)↑ MANF↑ CHOP and BATF2↓ Downstream genes CXCL9 and CXCL10↓	Involve the activation of MANF-MUC2 signaling pathway and the regulation of microbial homeostasis to promote the protection of damaged mucus barrier	[68]
C. sinensis	CSP	Cy-treated intestinal barrier injury female BALB/c mice model	25, 50, and 100 mg/kg b.w. for 7 days	Increased the goblet cells and mucins area	Nm	IAP, DAO, EGF and EGFR↑ ZO-1 and Claudin-1↑ MLCK, p-MLC↓ p-ERK↑ p-JNK and pp38↓	Attenuate Cy-induced intestinal barrier injury associated with mitogen-activated protein kinases (MAPKs) pathways	[69]
C. sinensis	CSP	Cy-treated intestinal barrier injury female BALB/c mice model	25, 50, and 100 mg/kg b.w. for 8 days		Lactobacillus↑ Bifidobacterium↑ Bacteroides↑ Clostridium↓ Flexispira↓	TNF-α, IL-2 and IL-21↑	Recover Cy-induced intestinal mucosal immunosuppression by regulating Th cells differentiation via stimulating cytokines secretion and transcription factors production may associated with TLRs and NF-κB pathwayReversed the levels of SCFAs in colon and restored Cy-induced gut microbial dysbiosis by modulating microbial community structure and composition	[70]
I. obliquus	IN	STZ induced type 2 diabete (SPF)-grade Kunming mice model	150, 300, and 600 mg/kg b.w. for 9 weeks	Increase the expression levels of the Ki-67, ZO-1, and MUC2 genes	Firmicutes↑ Bacteroidetes↓	Ki-67↑ ZO-1 and MUC2↑ IL-6 ↓	Protected against diabetes mellitus by ameliorating intestinal barrier dysfunction. IN also suppressed the pro duction of proinflammatory cytokines, enhanced the function of the intestinal mucosal mechanical barrier, promoted the proliferation of beneficial bacteria and reduced the abundance of pathogenic bacteria, thereby ameliorating diabetes mellitus	[71]
T. fuciformis	TFP	1. DSS-induced male BALB/c mice UC model	50, 100, and 200 mg/kg b.w. for 7 days	Increase mucuslayer thickness in colitis mice Lead to higher expression levels of Muc-2 and Clca1	Nm	TNF-α, IL-1β and IL-6↓ ZO-1 and OCLN (occludin)↑	The clinical symptoms and histopathological changes of DSS induced UC mouse model were significantly improved, and inflammatory cell infiltration was inhibited. Its mechanism is closely related to the restoration of intestinal barrier integrity	[72]
T. fuciformis	TFP	2. LPS-stimulated Caco-2 cells model	TFP dose at 25, 50 and 100 μg/mL	Upregulate the expression of TJP1, OCLN, Clca1 and Muc-2		IL-1β and IL-6↓ TNF-α↓ TER↑ FITC-dextran↓ (LPS-stimulated Caco-2 cells)
A. auricula	AAPs DAAPs (prepared from AAPs by alkaline treatment)	High-fat and high-cholesterol diet combined with carbon tetrachloride(HFHCD/CCl₄) induced nonalcoholic fatty liver disease (NAFLD) male C57BL mice model	200 mg/kg b.w. for 8 weeks	AAPs and DAAPs recoverd the expression of Muc-2, ZO-1, Occludin and Claudin-1	Firmicutes to Bacteroidetes ratio (F/B)↓ Allobaculum↓, Olsenella↓, Ruminococcus 2↓ Clostridium_XVIII↓ Lactobacillus↑ Bifidobacterium↑ Dorea and Odoribacter↑	TNF-α, MCP-1, NF-κB and TLR4↑ Col1a1↓	Protective effects were closely related to alleviating gut microbiota disturbance, keeping the intestinal barrier, altering the BAs profile and regulating the mRNA expression of BAs metabolism	[73]

Source	Name	Model	Dosages and time	Effect on intestinal mucosal barrier	Effect on intestinal flora	Protein/mRNA expression	Mechanism	Reference
Safflower	SPS	DSS-induced colitis C57BL mice model	60, 120, 180 mg/kg for 14 days	Improve mucosal barrier function and colon epithelial integrity in UC mice Increase the expression of ZO-1, Occludin, Claudin-1, and MUC2	Limosilactobacillus↑ Akkermansia↑ Bacteroides↓ Bifidobacterium↑ unidentified_Lachnospiraceae↑	Reg-3β, Reg-3g, and Reg-3γ↑	Achieved through inhibiting the activation of the STAT3/NF-κB signaling pathway related to the inflammatory factor CHI3L1, regulating the disorder of intestinal flora	[74]
Apple	MAP	1, 2-DMH and DSS induced colorectal adenocarcinoma	Basal diets mixed with different doses of MAP (1.25%, 2.5% and 5%, m/m) for 7−20 weeks	Nm	Nm	MUC1↓ A lower β-catenin level in the nucleus, while a higher β-catenin level in the cytoplasm, compared with that of model group	Lie in that MAP affected the ex pression and function of MUC1 and promoted the translocation of β-catenin from nucleus to cytoplasm	[75]
Gracilaria lemaneiformis	SP	DSS-induced colitis BALB/c mice model	200, 400, 600 mg/kg for 4 weeks	SP treatments, protective effects of high dose SP was confirmed by 21.82%, 43.65% and 97.11% Respectively increase positive region of Claudin-1, ZO-1 and MUC-2	Actinobacteria↑ Corynebacterium_1↑ Enterorhabdus↑ Bacteroides↓	TNF-α, IL-6, IL-1β↓ SCFA, GPR43, GPR109A and Olfr78↑	Alleviate DSS-induced colitis via enhancing intestinal barrier, reducing inflammation, activating SCFA receptors and regulating gut microbiota	[76]
Mesona chinensis Benth	MBP	DSS-induced colitis C57BL/6 mice model	12.5, 25, 37.5 mg/kg for 15 days	Significantly increase the level of occludin, ZO-1 and MUC-2 proteins	Helicobacter↓ Prevotella↓ Lactobacillus↑ Coprococcus↑	MPO, TNF-α and IL-1β↓ IL-10↑ SOD, CAT and GSH-Px MDA↑	Regulates the anti-inflammatory effect of intestinal cells by restoring the intestinal barrier, may be related to the MAPK/NF-κB signaling pathway	[77]
Lycium barbarum	LBP	DSS-induced colitis C57BL/6 mice model	150, 300 mg/kg for 30 days	Significantly improve the colonic tissue structure by upregulating MUC-2, claudin-1, and ZO-1 protein expression	Akkermansia↑ Bifidobacterium↑ Turicibacter↓ Clostridium_sensu_stricto_1↓ Escherichia-Shigella↓ Faecalibaculum↓	IL-1β, IL-6, and TNF-α↓ MPO↓ DCA↑ TGR5↑	Boost the abundance of Dubosiella in intestinal microbiota, rincreasing LCA, DCA and the expression of TGR5, ultimately strengthening the intestinal barrier, influenced by the change in the abundance of Dubosiella	[78]
Sea cucumber body wall (Thelenota ananas)	Ta-FUC	Simulated saliva-gastrointestinal digestion	4.0 mg/mL	FUC could facilitate interaction with the intestinal mucosa at pH 7.0, maintain the integrity of the intestinal mucosa, and be a potential material for designing colonic administration delivery systems	Proteobacteria↓ Bacteroidota/Firmicutes↑	Nm	Exhibit higher adhesive function in the intestinal environment than in the gastric environment. The main supramolecular interactions were identified as disulfide bonding, hydrogen bonding, and hydrophobic interactions for intensity, prolonging the retention of FUC in the intestinal mucosa and build a three-dimensional network, helping improve the MUC barrier properties against mucosal delivery of functional components in the intestinal tract	[79]
Atractylodes macrocephalae Koidz.	AMP	DSS-induced acute colitis C57BL/6 mice model	100 mg/kg for 14 days	The mRNA expressions of Claudin-1, Occludin, and ZO-1 increased The expression of MUC-1 was higher (not remarkable); MUC-2 was significantly increased in DSS + AMP group	Enterococcus↓ Lactobacillus↑	TNF-α, IL-1β, IL-6↓	Suppress the generation of proinflammatory cytokines such as IL-1β, IL-6 and TNF-α as well as the infiltration of neutrophils in colon; strengthen chemistry barrier and intestinal TJ through boosting the expressions of MUC-2 and Claudin-1; promote the proliferation of beneficial bacteria, and inhibits harmful bacteria, thereby ameliorate colitis induced by DSS	[80]
Sea buckthorn	SBP	High-fat diet (HFD) induced mice cognitive dysfunctions C57BL/6 male mice model	HFD chow containing 0.1% SBP (m/m) for 12 weeks	SBP in diet significantly reversed the mucus layer impairments and improved MUC-2 expression. SBP in the diet significantly raised the expression of Claudin-1, ZO-1 and Occludin	Ileibacterium↑ Lactobacillus↓ Dubosiella↓ Olsenella↓ Helicobacter↓ Ruminiclostridium_9↓	TNF-α/IL-1β/IL-6↓ NF-κB pathway↓ CREB/BDNF/TrkB pathway↑	The reversal effects of SBP on gut dysbiosis might be the important reason for its positive effects on cognitive dysfunction induced by HFD in mice	[81]
Momordica charantia	MCP	1. DSS-induced colitis C57BL/6 mice model 2. Pseudo-sterile mouse model (FMT experiment) 3. LPS-induced inflammation in RAW264.7 cells model	200 and 500 mg/kg for 7 days__	Significantly elevate mRNA and protein expression levels of MUC2	Parabacteroides↑ Allobaculum↑ Ruminococcus↑ Allobaculum↓ Dorea↓ Sutterella↓	Reg3b, Reg3g and Ki67↑	Alleviate inflammation in colitis mice by alleviating DSS induced intestinal barrier damage, regulating intestinal flora and inflammatory pathways	[82]
Blackened jujube	BJP-4	DSS-induced colitis C57BL/6 mice model	100, 200 and 400 mg/kg for 7 days	After the administration with BJP-4, there was upregulation in the relative expression level of ZO-1 and MUC-2	f_Muribaculaceae↑ Lactobacillus↑ Lachnospiraceae_NK4A136_group↑ o_Clostridia_UCG-014↓ Bacteroides↓ Escherichia-Shigella↓	IL-6 and TNF-α↓ IL-10↑ SOD and CAT restored, MDA↓ TLR4/MyD88/NF-κB/NLRP3 signaling pathway↓	BJP-4 dose-dependently alleviated DSS-induced colitic symptoms through altering gut micro biota structure, modulating TLR4/MyD88/NF-κB/NLRP3 pathway, rebalancing pro/anti-inflammatory cytokines, improving oxidative sta tus, enhancing the integrity of the intestinal epithelial barrier and pro moting the production of SCFAs. The gut microbiota played a central role in anti-inflammatory activity	[83]
Dendrobium fimbriatum	cDFPW1	1. DSS-induced colitis C57BL/6 mouse model 2. Co-culture system consisting of intestinal organoids and LPLs from the colon of mice in Matrigel at a ratio	200 mg/(kg∙day) for 21 days	Directly promote the proliferation of intestinal epithelial cells to protect the integrity of intestinal mucosa and contribute to alleviate DSS-induced colitis	Nm	IL-1β, IL-6, IL-17, IL-23, CXCL1, McP-1, MIP-1α and MIP-1β↓ IL-10, IL-22 and IFN-γ↑	Promote the regeneration of ISCs to protect the integrity of intestinal mucosa via LPLs secreted IL-22, thus playing an important role in ameliorating UC	[64]
C. pilosula	sC-CCP-2	Intestinal adhesion experiment of composite membrane in vitro	5 mg/mL	The sulfhydryl group on the surface of sC-CCP-2 forms a disulfide bond with the cysteine residue on the protein on the surface of LGG, forming a adhesion between LGG and the mucus, and increasing the viscosity of the mucus to LGGAdhesion	Nm	Nm	sC-CCP-2/LGG can form adhesion between sC-CCP-2 and mucus, and the adhesion force between SC-CCP-2 and mucus is the strongest. sC-CCP-2 can increase the intestinal adhesion of LGG, prolong the residence time of LGG in the intestine, and promote the intestinal adhesion and colonization of LGG	[62]