1. Introduction

2. Human Gut Microbiota

3. The Influence of Human Metabolic Diseases on Gut Microbiota

4. The Role of Gut Microbiota-Derived Metabolites in Human Disease Treatment

5. BPs and Their Therapeutic Potential

5.4. Mechanism of Actions of Gut Microbiota Mediated BPs in Metabolic Disease Treatment

The dietary intake of BPs has been shown to reduce the prevalence of (or alleviate) certain metabolic diseases, including obesity, T2DM, NAFLD, and CVD. Representative studies related to the potential of BPs in relieving metabolic diseases via modulation of gut microbiota are listed in Table 1, Table 2, Table 3 and Table 4.

5.4.1. Treating Obesity

Obesity has caused serious economic and health problems in the world, and which characterized by weight gain, fat deposition, and abnormal lipid metabolism [201]. Obesity is a chronic metabolic disease caused by the interaction of multiple factors such as genetic and environmental factors. Its mechanism of occurrence is that energy intake exceeds energy expenditure, leading to excessive accumulation of fat and abnormal weight in the body (Figure 3). Recently, accumulated research has shown that dietary BPs could treat obesity (Table 1). BPs in treating obesity involve their interaction with the gut microbiota, leading to relieving gut dysbiosis and a range of effects that can influence metabolic health and body weight. Some of these potential mechanisms include: First, BPs can serve as prebiotics, providing substrates for the growth of beneficial gut bacteria such as Bifidobacteria, Faecalibaculum, and Lactobacilli, etc [173,202,203]. By promoting the proliferation of these beneficial microbes, BPs (for example, Seabuckthorn polysaccharide, Lycium barbarum polysaccharide, and Laminaria japonica polysaccharide) help rebalance the gut microbiota composition, which is often disrupted in obesity [173,202,203]. Second, fermentation of BPs by gut bacteria can directly yield SCFAs, particularly (95%) acetate, propionate, and butyrate. Butyrate is largely consumed by colonocytes, propionate is mainly metabolized in the liver, leaving acetate the most abundant SCFAs in the peripheral circulation. These SCFAs play a role in energy regulation, appetite control, and lipid metabolism, and have implications for obesity management. Third, BPs have been linked to the preservation of gut barrier function by directly maintaining intestinal epithelial barrier integrity (regulating inflammatory cytokine expression, inhibiting oxidative stress, and upregulating tight junction protein expression) and indirectly regulating intestinal microbiota and immunity [204], which is vital in preventing metabolic endotoxemia and low-grade inflammation associated with obesity. By maintaining the gut barrier integrity, BPs may mitigate the impact of gut-derived inflammatory signals. Fourth, BPs can impact the secretion of gut hormones involved in appetite regulation and energy balance, such as decreasing leptin and ghrelin, increasing cholecystokinin (CCK), peptide YY (PYY), and GLP-1. By affecting the secretion of hormones such as leptin and ghrelin, these polysaccharides may help regulate food intake and reduce overeating, which is a significant factor in obesity. Some BPs, such as konjac glucomannan and alginate, have demonstrated the ability to regulate appetite by increasing satiety. They form a viscous gel in the gastrointestinal tract, leading to delayed gastric emptying and a prolonged sensation of fullness. This mechanism reduces calorie intake and aids in weight management. SCFAs are also able to induce intestinal and colonic L cells responsible for the secretion of GLP-1 and PYY. The induction is done through the activation of G protein-coupled receptors (GPR). By releasing GLP-1 and PYY, dietary BPs not only directly stimulate afferent neurons involved in satiety induction, but they also stimulate satiety by delaying gastric emptying and inducing the ileal break. Furthermore, SCFAs increase intestinal gluconeogenesis and thus stimulate sodium-glucose cotransporters in the portal vein to send a nervous afferent signal for the suppression of appetite [205]. This can lead to improved satiety and reduced food intake, contributing to weight management. Finally, the gut microbiota influenced by BPs can generate metabolic signals that communicate with the host, impacting energy metabolism and adipose tissue function. Certain BPs have been reported to inhibit the differentiation and proliferation of preadipocytes into mature fat cells (adipocytes). The excessive proliferation and differentiation of preadipocytes, along with the substantial accumulation of lipids in mature adipocytes, are central to the pathophysiological process of obesity [206]. Thus, these microbial-derived signals can potentially limit fat accumulation and aid in the prevention and treatment of obesity.

For example, Auricularia auricula polysaccharides (AAPs) administration attenuated HFD-induced weight gains, decreased abdominal fat deposits and adipocyte size and inhibited hepatic steatosis and dyslipidemia. Additionally, the anti-obesity effects of AAPs were confirmed to depend on the gut microbiota, as demonstrated by AAPs failed to attenuate the HFD-induced body weight gain and metabolic disorders when mice were treated with antibiotics [207]. In another study, AAPs treatment showed significant improvements in overweight, IR, glucose and lipid metabolism disorders, and liver damage in obese mice. In addition, AAPs ameliorated gut microbiota disorders markedly reduced the F/B ratio, and promoted the proliferation of beneficial bacteria like Roseburia, Bacteroides, and Allobaculum, which are known to produce SCFAs with multiple beneficial functions. For example, butyrate, produced by these genera, can improve intestinal barrier function by exerting anti-inflammatory and immunomodulatory effects [208], thereby improving endotoxemia, and decreasing the levels of inflammatory factors such as IL-6 and TNF-α. This study elucidated that AAPs improve obesity by regulating gut microbiota and TLR4/JNK signaling pathway, offering novel perspectives for further conclusion of the anti-obesity potential of AAPs [197].

Overall, the interplay between BPs, the gut microbiota, and host metabolic processes represents a complex yet promising area for understanding and potentially addressing obesity. Through their effects on the gut microbial environment, BPs hold the potential for modulating metabolic health and contributing to obesity treatment strategies.

Table 1. BPs with therapeutic potential against obesity.

Table 1. BPs with therapeutic potential against obesity.

Bioactive Polysaccharides	Monosaccharide Composition and Molecular Weight (Mw)	Dosage	Study Approaches	Major Findings	Mode of Action–Gut Microbiota	References
Auricularia auricula polysaccharide	Composed of mannose (50.84%), glucose (21.61%), xylose (9.24%), galactose (8.58%), glucuronic acid (5.78%) and fucose (3.96%); Mw: 1065.2 kDa	200 mg/kg	High-fat diet-induced obese mice model	Reduced body weight gain; Attenuated high-fat diet-induced metabolic disorders	Decreased Mucispirillum and increased Peptococcus, Muribaculum, Anaerovorax, and Papillibacter	[207]
Auricularia auricula polysaccharide	Composed of mannose (77.0%), galacturonic acid (12.8%), fucose (5.2%), xylose (3.2%), galactose (1.4%), and rhamnose (0.3%); Mw: 1210 kDa	50 and 100 mg/kg	High-fat diet-induced obese mice model	Ameliorated high-fat diet-induced IR, glucose, and lipid metabolism disorders; Protected intestinal barrier function	Reduced F/B ratio; Promoted Roseburia, Bacteroides, and Allobaculum; Increased levels of SCFAs, folate, and cobalamin	[197]
Astragalus polysaccharides	-	1,000 mg/kg	High-fat diet-induced obese mice	Reduced body weight, fat accumulation; Enhanced insulin sensitivity and glucose homeostasis	Enriched Bacteroides	[209]
Sargassum fusiforme fucoidan	Composed of carbohydrate (81.33%), uronic acid (12.53%), and sulfate (17.36%)	200 mg/kg	High-fat diet-induced obese mice	Reduced fasting blood glucose and IR index along with improved glucose tolerance; Elevated hepatic antioxidant enzymes	Increased the abundance and diversity of gut microbiota	[210]
Ganoderma lucidum mycelium polysaccharides	Mw: >300 kDa	4% and 8%	High-fat diet-induced obese mice	Reduced body weight, inflammation, and IR; Improve intestinal barrier integrity	Decreased F:B ratio; Enhanced Parabacteroides goldsteinii, Bacteroides spp., Anaerotruncus colihominis, Roseburia hominis, Clostridium methylpentosum; Reduces metabolic endotoxemia	[211]
Hirsutella sinensis polysaccharides	Mw: >300 kDa	20 mg/kg	High-fat diet-induced obese mice	Enhanced gut integrity, reduced intestinal and systemic inflammation, and improved insulin sensitivity and lipid metabolism	Selectively promoted the growth of Parabacteroides goldsteinii	[212]
Ganoderma lucidum polysaccharides	-	150 mg/kg	High-fat diet-induced obese mouse model	Inhibited serum and hepatic lipid metabolic disorders; Alleviated hepatic steatosis and gut microbiota dysbiosis	Increased Alloprevotella, Parabacteroides, Parasutterella, Bacteroides, decreasing Blautia, Enterorhabdus, and Roseburia; Increased fecal butyric acid and BAs levels	[213]
Ganoderma amboinense polysaccharides	Composed of glucose (52.54%), mannose (15.78%), galactose (27.16%) and fucose (4.21%)	100 and 200 mg/kg	High-fat diet-induced obese mice model	Prevented weight gain and fat accumulation; Improved glucose tolerance; Reduced serum and liver lipid concentrations and inflammation	Prevented obesity by regulating the abundance of Parabacteroides, Bacteroides, and Lachnospiracea_incertae_sedis; Altered microbial lipid metabolism, glycan biosynthesis	[175]
Ganoderma lucidum polysaccharides	-	150 mg/kg	High-fat diet-induced obese golden hamster model	Improved blood lipid profiles; Elevated the relative abundances of beneficial bacteria	Enhanced Prevotella, Oscillibacter, and SCFA-producers	[195]
Edible brown seaweed Undaria pinnatifida	Composed of mannuronic acid and guluronic acid at a ratio of 0.7; Mw: 800 kDa	300 mg/kg	High-fat diet-induced obese mice model	Improved body composition, fat deposition in body tissues and organs, lipid abnormality, and inflammatory response	Increase in Bacteroidales and reduction in both Clostridiales and Lactobacillales	[214]
Lycium barbarum polysaccharides	Composed of D-mannose, L-rhamnose, D-glucose, D-galactosamine and D-xylose	0.2% in drank water	High-fat diet-induced obese mice model	Decreasing serum total triglycerides and total cholesterol levels; Elevating serum high-density lipoprotein cholesterol	Reduced F/B ratio; Increased SCFA-producing bacteria Lacticigenium, Lachnospiraceae_NK4A136_group, and Butyricicoccus; Increased fecal SCFAs level	[174]
Lycium barbarum polysaccharide	Composed of fucose, rhamnose, amino-galactose, galactose, glucose, mannose, and fructose with the molar ratio of 0.02: 0.08: 0.03: 0.11: 46.67: 0.37: 4.72; Mw: 3.74 kDa	150 mg/kg	High-fat diet-induced obese mice model	Increased weight loss, lowering FFA levels in serum and liver; Increased adiponectin and decreased fatty acid synthase gene expression in liver	Increased gut microbial β-diversity; Reduced F/B ratio; Enhanced Faecalibaculum, Pantoea, and uncultured_bacterium_f_Muribaculaceae	[202]
Saccharina japonica fucan	Composed of Fuc (5.2%), 1,3-linked Fuc (63.6%), 1,4-linked Fuc (3.2%), 1,2-linked Fuc (0.9%), 1,3,4-linked Fuc (5.9%) and 1,2,3-linked Fuc (21.2%); Mw: 5.1 kDa	0.6 mg/mL solution in drinking water	High-fat diet-induced obese mice model	Suppressed high-fat diet-induced obesity, blood glucose metabolic dysfunction, dyslipidemia, and gut microbiota dysbiosis	Enhanced Bacteroides sartorii and Bacteroides acidifaciens; Increased fucoidan-degrading bacteria	[215]
Laminaria japonica fucoidan	Composed of fucose, galactose, mannose, xylose, glucose, and galacturonic acid in a molar ratio of 7.5: 1.0: 0.6: 0.2: 0.3: 0.3; Mw: 627.5 kDa	300 mg/kg	High-fat diet-induced obese mice model	Ameliorated body weight gain, fat accumulation, IR, and adipocyte hypertrophy	Reduced F/B ratio; Greater relative abundance of the phylum Bacteroidetes and the families Muribaculaceae and Bacteroidaceae; Enhanced SCFAs production	[216]
Laminaria japonica polysaccharides	Composed of rhamnose, galacturonic acid, and glucose in a respective mass ratio of 11.6:10.1:78.2; Mw: 31.7 kDa~1700 kDa	75 mg/kg	High-fat diet-induced obese mice model	Induced weight loss, reduced liver fat accumulation, reduced TC and LDL-C levels, reduced intestinal tissue inflammation	Reduced F/B ratio; Increased Bacteroides acidifaciens, Lactobacillus intestinalis, and Lactobacillus murinus	[203]
Laminaria japonica polysaccharides	Composed of high content of uronic acid and fucose; Mw: 600 kDa	0.25% in diet	High-fat diet-induced obese mice model	Reduced body weight gain; Reduced fat accumulation in the liver and adipose tissues	Increased gut microbial diversity and the abundance of Rikenellaceae and Bacteroidales S24_7 group; Increased gut microbial SCFAs production	[217]
Microalgae polysaccharides	Composed of rhamnose (38.6%), glucosamine (21.23%) and glucuronic acid (10.56%); Mw: 660 or 3640 kDa	400 mg/kg	High-fat diet-induced obese mice model	Protection against overweight, glucose tolerance impairment, dyslipidemia, and fat deposition in the liver	Increased Clostridia, Bacterioidia, and Mollicutes and decreased Actinobacteria and Verrucomicrobia; Altered metabolism of SCFAs, secondary BAs, and trimethylamine	[218]
Seabuckthorn polysaccharide	Composed of rhamnose, arabinose, galactose, glucose, and galacturonic acid, the molar ratios of which were 2.1:44.6:19.7:28.2:5.3; Mw: 9940 Da	0.1% in diet	High-fat diet-induced obese mice model	Reduced body weight gain, serum lipid level, and liver triglycerides level; Elevated p-AMPKα and PPARα proteins expression in liver	Increased Muribaculaceae_unclassified, Bifidobacterium, Rikenellaceae_RC9_gut_group, Alistipes, and Bacteroides, and decreased Lactobacillus, Dubosiella Bilophila, and Streptococcus; Increased fecal SCFAs level	[173]
Bletilla striata polysaccharides	Composed by mannose and glucose in a molar ratio of 2.946:1; Mw: 373 kDa	300 mg/kg/d	High-fat diet-induced obese mice model	Reduced the abnormal weight gain; Altered amino acid, purine, pyrimidine, ascorbate, and aldarate metabolisms in feces, urine, and liver	Reduced F/B ratio; Increased Turicibacter, Romboutsia, and Anaerostipes, and decreased Bacillus, Helicobacter, and Colidextribacter	[219]
Aspergillus cristatus polysaccharide	Composed of ribose, glucose, galactose, and mannose in a molar ratio of 1:1.7:4.4:5.2; Mw: 21.16 kDa	400 mg/kg/d	High-fat diet-induced obese rats model	Decrease body weight gain, adipose tissue weight, and the liver/body weight ratio; Improve IR	Increased Akkermansia, Akkermansia muciniphila, Bacteroides, Romboutsia, Blautia, and Desulfovibrio; Increased fecal SCFAs level; Elevated the content of unconjugated and conjugated BAs in the serum and liver	[220]
Raspberry polysaccharide	Composed of mannose, rhamnose, glucose, galactose, arabinose, and fucose in a molar ratio of 0.06: 0.33: 1.00: 0.08: 0.31: 0.15; Mw: 18 kDa	400 mg/kg	High-fat diet-induced obese mice model	Decrease body weight gain, hyperlipidemia, inflammation, and fat accumulation; Enhance intestinal barrier integrity	Reduced F/B ratio; Increased Ruminococcaceae_UCG − 014, Lactobacillus taiwanensis, Bifidobacterium pseudolongum, and Turicibacter; Increased fecal SCFAs level and decreased LPS level	[221]
Raspberry polysaccharide	Composed of arabinose (39.76 %) and galactose (39.43 %); Mw: 74.86 kDa	100 mg/kg	High-fat diet-induced obese mice model	Decrease body weight gain, hyperglycemia, hyperlipemia, endotoxemia, hepatic inflammation, and oxidant stress; Enhance intestinal barrier integrity	Increased Dubosiella, Blautia, and Acetatifactor; Increased fecal butyrate production	[222]

Notes: IR, insulin resistance; FFA, free fatty acid; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; BAs, bile acids; SCFAs, short-chain fatty acids; p-AMPKα, phosphorylated adenylate activated protein kinase α; PPARα, peroxisome proliferator-activated receptor α; F:B ratio, the ratio of Firmicutes to Bacteroidetes.

5.4.2. Anti-T2DM

Diabetes, which is primarily characterized by high blood glucose, is a metabolic disorder syndrome of sugar, proteins, and fat caused by the dysfunction of pancreatic islets and IR. IR is the primary pathophysiology underlying metabolic syndrome and T2DM. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in IR. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host’s overall energy extraction, thereby playing a role in the pathogenesis of obesity and prediabetes [223]. Takeuchi et al. provide a comprehensive view of the host–microorganism relationships in IR, revealing the impact of carbohydrate metabolism by microbiota, especially the role of Alistipes indistinatus in T2DM treatment, suggesting a potential therapeutic target for ameliorating IR [223]. BPs as carbohydrates play an important role in the treatment of T2DM (Table 2 and Figure 3). BPs in treating T2DM involve their interaction with the gut microbiota and subsequent effects on glucose metabolism and insulin sensitivity. Here are some of the key mechanisms: First, BPs can act as prebiotics, providing a source of nutrients for beneficial gut bacteria. By promoting the growth of these beneficial microbes, for example, Faecalibacterium, Lactobacillus, Bifidobacterium, and Akkermansia, and BPs can help restore the balance of the gut microbiota, which is often altered in individuals with T2DM. Several results indicated that BPs, Auricularia auricula polysaccharides (AAPs) can improve the disorders of glucose by regulating the structure of the gut microbiota. AAP intervention effectively stabilized the body weight, reduced fasting blood glucose levels, and decreased the abundance of Enterorhabdus, Desulfovibrio, and Helicobacter, increased the abundance of beneficial genera such as Alloprevotella, Faecalibaculum, Dubosiella of T2DM mice [224]. Another study reported that AAPs treatment decreased the abundance of Allobaculum and Clostridium and increased the abundance of Bacteroides and Lactobacillus to exert an anti-diabetic effect [225]. In addition, serum IR of diabetic mice was significantly improved by restoring lipid metabolism, amino acid metabolism, and glycerophospholipid pathways after AAP treatment in T2DM mice [226]. Second, fermentation of BPs by gut bacteria can result in the production of SCFAs. SCFAs have been shown to improve glucose homeostasis by enhancing insulin sensitivity and reducing hepatic glucose production. Third, BPs have been found to improve gut barrier integrity. A compromised gut barrier allows endotoxins to enter the bloodstream, triggering chronic low-grade inflammation, IR, and T2DM. By maintaining gut barrier function, BPs may help reduce inflammation and improve insulin sensitivity. Dendrobium officinale polysaccharide showed favorable growth-promoting effects on Parabacteroides distasonis to derive nicotinic acid, which fortifies intestinal barrier function via activating intestinal GPR109a, leading to ameliorating IR and treating T2DM [227]. Fourth, BPs can influence the secretion of gut hormones involved in glucose regulation, such as GLP-1 and PYY. GLP-1, for example, stimulates insulin secretion, inhibits glucagon release, and promotes satiety. By modulating the secretion of these hormones, BPs may help regulate blood glucose levels in individuals with T2DM. Increased fasting blood glucose (FBG) is the most typical and important symptom of T2DM. Shao et al. treated the HFD and streptozotocin (STZ)-mice with polysaccharide F31 from G. lucidum fruit bodies and found that F31 could decrease the FBG, HOMA-IR, and fasting serum insulin (FSI) levels of T2DM mice. In addition, F31 treatment improved the composition of intestinal microbiota in diabetes mice, significantly decreased the F/B ratio, F31 also increased the abundance of Lactobacillus, Bacteroides, and Ruminococcaceae. Correlation analysis showed Bacteroides and Blautia showed a positive relationship with FBG and homeostasis model assessment-estimated IR (HOMA-IR). Lactobacillus and norank_f__Muribaculaceae were negatively associated with FBG and HOMA-IR [228]. In practical application, Chen et al. found that GLP could regulate gut microbiota and fecal metabolites in high-fat diet and streptozotocin-induced T2DM rats. GLP intervention (400 mg/kg) significantly decreased the levels of fasting blood glucose and insulin. Furthermore, GLP reduced the abundance of harmful bacteria, like Aerococcus, Ruminococcus, Corynebactrium, and Proteus, while increasing the level of Blautia, Dehalobacterium, Parabacteroides, and Bacteroides. Meantime, GLP could restore the disordered amino acid metabolism, carbohydrate metabolism, and inflammatory substance metabolism of intestinal bacterial communities [229]. Another study also found that Ganoderma amboinense polysaccharide can accelerate the glucose utilization rate of HFD mice, reduce FBG levels, and increase the relative abundance of Parabacteroides, Bacteroides, and Lachnospiracea_incertae_sedis [175]. Additionally, chronic inflammation is closely associated with the development of IR and T2DM. BPs with anti-inflammatory properties can help reduce inflammation by inhibiting the production of pro-inflammatory cytokines and modulating immune responses within the gut and systemically.

These gut microbial mechanisms collectively contribute to the potential benefits of BPs in treating T2DM. By positively influencing gut microbiota composition, SCFA production, gut barrier function, gut hormone secretion, and inflammation, BPs hold promise in improving glucose homeostasis and insulin sensitivity. However, it’s important to note that further research is needed to fully understand and utilize these mechanisms for therapeutic purposes. It is always recommended to consult with healthcare professionals for proper management of T2DM.

Table 2. BPs with therapeutic potential against T2DM.

Table 2. BPs with therapeutic potential against T2DM.

Bioactive Polysaccharides	Monosaccharide Composition and Molecular Weight (Mw)	Dosage	Study Approaches	Major Findings	Mode of Action–Gut Microbiota	References
Acidic tea polysaccharides	Mw: 3.9285 × 104 Da	200, 400 and 800 mg/kg	High-fat diet-streptozotocin-induced rat models	Improve plasma and liver lipid metabolism	Increased Bifidobacterium, Blautia, Dorea, and Oscillospira, and reduction in Desulfovibrio and Lactobacillus; Improved secondary BA biosynthesis and primary BA biosynthesis	[230]
White hyacinth bean polysaccharides	Composed of glucose, rhamnose, galactonic acid, galactose, xylose, and arabinose in the molar ratio of 23.23: 6.2: 5.09: 2.76: 2.4: 0.48; Mw: 2.3 × 105 Da	100 mg/kg	High fat and high sugar induced T2DM rat model	Reduction of blood glucose levels and improvement of intestinal impairment	Increased gut microbiota diversity and F/B ratio; Enriched Allobaculum, Eubacterium, Anarrobiospirillum, and Holdemania; Increased cecal SCFA level	[164]
Fu brick tea polysaccharides	Composed of arabinose (57.4%), rhamnose (25.2%), galactose (5.1%), mannose (3.3%), galacturonic acid (3.9%) and glucuronic acid (3.1%); Mw: > 8000 Da	200 and 400 mg/kg	High-fat diet-streptozotocin-induced rat models	Relieved dyslipidemia (i.e. TC, TG, LDL-C, and HDL-C), IR, and pancreas oxidative stress	Increased Ruminococcus and Lactobacillus; Reduced Prevotella and Faecalibaculum; Elevated colonic SCFA levels	[176]
Fructus mori polysaccharides	Mw: 102.22 kDa, 8.71 kDa, and 5.62 kDa	600 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Suppressed intestinal inflammation and oxidative stress; Enhanced the intestinal barrier function	Inhibiting endotoxin-producing Shigella and promoting Allobaculum and Bifidobacterium	[177]
Dendrobium officinale polysaccharides	β-glucan; Mw: 8000~12000 Da	400 mg/kg/d	High-fat diet-induced T2DM mice model	Ameliorating IR; Fortifies intestinal barrier function	Favorable growth-promoting effects on Parabacteroides distasonis; Increased nicotinic acid level	[227]
Auricularia auricula polysaccharides	Composed of fucose, galactose, glucose, mannose, and glucuronic acid	200 mg/kg/d	High-fat diet-streptozotocin-induced T2DM mice model	Reduced fasting blood glucose level; Stabilized the weight	Decreased the abundance of Enterorhabdus, Desulfovibrio, and Helicobacter, and increased the abundance of beneficial genera such as Alloprevotella, Faecalibaculum, Dubosiella	[224]
Sargassum fusiforme fucoidan	High sulfate (14.55%) and rich in fucose (55.67%) and galactose (20.83%); Mw: 205.8 kDa	40 mg/kg/d	High-fat diet-streptozotocin-induced T2DM mice model	Decreased fasting blood glucose, improved glucose tolerance, decreased oxidative stress	Enriched Bacteroides, Faecalibacterium, and Blautia; Increased levels of (R)-carnitine and choline in the colon	[165]
Auricularia auricula-judae polysaccharides	Composed of mannose (62%), glucose (12.6%), galactose (4%), rhamnose (13.1%), xylose (4%) and fucose (3.8%)	50 and 100 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Decreased inflammation, liver injury, and IR; improved glycolipid metabolism disorders by regulating the AKT and AMPK pathways	Elevated gut microbiota diversity; Increased Lactobacillus and Bacteroides; Decreased Clostridium and Allobaculum; Affected the amino acid metabolism and glycolipid metabolism pathways	[225]
Auricularia auricula-judae polysaccharides	Composed of arabinose, mannose, galactose, and xylose with a molar ratio of 15.59:1.52:4.76:1.0	200 mg/kg	High-fat diet-induced hyperlipidemia rat model	Reduce the levels of total cholesterol and LDL-C	Enriched several lower-abundance SCFA-producing bacteria such as Flavonifractor and Clostridium cluster IV	[231]
Ganoderma lucidum polysaccharides	Composed of arabinose (5.32%), galactose (5.47%), glucose (57.63%), xylose (0.84%), mannose (25.41%), ribose (1.95%) and rhamnose (3.38%)	500 and 1000 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Repaired islet cells and increased insulin secretion, promoted the liver synthesis and storage of glycogen; improved antioxidant enzymes and IR	Decreased the F/B ratio; Enriched Lactobacillus, Bacteroides, and Ruminococcaceae; Decreased the release of endotoxins	[228]
Ganoderma lucidum polysaccharides	Composed of mannose, glucose, galactose, rhamnose, and arabinose in the molar ratio of 3.16: 16.17: 3.74: 1.65: 1; Mw: 13.7 kDa	400 mg/kg	High-fat diet-streptozotocin-induced T2DM rat model	Decreases in the levels of fasting blood glucose and insulin	Reduced Aerococcus, Ruminococcus, Corynebacterium, and Proteus, and increased Blautia, Dehalobacterium, Parabacteroides, and Bacteroides; Restored the disturbed amino acids metabolism, carbohydrates metabolism	[232]
Lycium barbarum polysaccharides	Composed of carbohydrates (62.27%), uronic acid (25.03%), and protein (2.92%); Mw: 3.5 kDa	50, 100, or 200 mg/kg	High-fat diet-streptozotocin-induced T2DM rat model	Alleviated the symptoms of hyperglycemia, hyperlipidemia, and IR; boosted the activities of CAT, SOD, and GSH-Px and reduced inflammation	Increasing Bacteroides, Ruminococcaceae_UCG-014, Intestinimonas, Mucispirillum, Ruminococcaceae_UCG-009 and decreasing Allobaculum, Dubosiella, Romboutsia; Increased SCFA production and decreased LPS	[233]
Lycium barbarum L. polysaccharides	Composed of rhamnose (8.37%), glucuronic acid (2.21%), glucose (7.95%), galactose (26.38%), xylose (7.91%) and arabinose (47.18%); Mw: 38.54 kDa	200 mg/kg	High-fat diet-streptozotocin-induced diabetes mice model	Improved fasting blood glucose and glycated hemoglobin level and beta-cell function; guarded the intestinal barrier function	Induced Allobaculum	[234]
Dendrobium officinale leaf polysaccharides	Composed of glucose, mannose, glucuronic acid, and galactose at a molar ratio of 3.2:2.6:1.0:0.7; Mw: 9.91 kDa	200 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Ameliorated hyperglycemia, inhibited IR, reduced lipid concentration	Decreased the F/B ratio; Increased Lactobacillus, Bifidobacterium, and Akkermansia; Increased colonic SCFA levels	[235]
Morchella esculenta polysaccharides	Composed of mannose (5.77%), glucose (81.35%), galactose (3.543%) and arabinose (8.99%)	200, 400, and 600 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Regulated hyperglycemia and hyperlipidemia and improved insulin sensitivity; Improved intestinal permeability	Increased Lactobacillus, decreased Corynebacterium, and Facklamia; Increased indole biosynthesis and secondary BA biosynthesis gene expression	[236]
Astragalus membranaceus polysaccharides	Mw: >3000 Da	400 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Improved glycolipid metabolism disorders, inflammation and oxidative stress levels, and organ injury; Improved intestinal barrier	Inhibited Shigella and promoted Allobaculum and Lactobacillus	[237]
Dendrobium officinale polysaccharides	Composed of mannose and glucose at a molar ratio of 3.45:1	200 mg/kg	High fat and high sugar and streptozotocin-induced prediabetic mice model	Improved glucose, IR, and lipid metabolism	Decreased F/B ratio; Increased Bifidobacterium and Lactobacillus and decreased Colidextribacter, Helicobacter, and Mucispirillum; Increased intestinal SCFAs level and decreased LPS level	[238]
Huanglian polysaccharides	Composed of glucuronic acid, glucose, galactose, and arabinose, with a molar ratio of 1.0:4.4:2.4:0.6; Mw: 12.1 kDa	200 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Improved hyperglycemia, IR, blood lipid levels, and β-cell function	Increased Akkermansia, and decreased Aerococcus, Providencia, Pseudochrobactrum; Increased fecal butyrate level	[239]
Laminaria japonica polysaccharide	Composed of fucose, galactose, glucose, and mannuronic acid, with a molar ratio of 0.848:0.097:0.039:0.016; Mw: 7.32 kDa	100 or 200 mg/kg	High fat and high sugar and streptozotocin-induced diabetic mice model	Reduced fasting blood glucose levels, insulin levels, and inflammatory factors	Increased Candidatus_Saccharimonas, Shinella, Akkermansia, and Ochrobactrum; Increased cecal SCFA level	[240]
Black quinoa polysaccharide	Composed of mannose (0.560%), ribose (0.418%), rhamnose (0.467%), glucuronide (1.889%), galacturonic acid (0.388%), glucose (91.169%), galactose (2.512%), xylose (0.305%), arabinose (2.031%), and fucose (0.262%); Mw: 8.087 kDa	400 or 800 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Ameliorated blood glucose and lipid levels and improved oxidative stress levels and liver injury levels	Decreased F/B ratio; Increased Dubosiella, Akkermansia, Faecalibaculum, and Allobaculum; Increased cecal SCFA level	[241]
Phellinus linteus polysaccharide	-	300 mg/kg	High fat and high sugar and streptozotocin-induced T2DM rat model	Promoted the secretion of GLP-1, stimulated insulin secretion, and reduced blood glucose	Increased Bacteroides, Parabacteroides, and Alistioes; Increased intestinal SCFAs production, and promoted conjugated BAs decomposition and the transformation of primary BAs to secondary BAs	[242]
Tegillarca granosa polysaccharide	Composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, and fucose, with a molar ratio of 1:1.38:0.87:0.53:0.52:5.37:1.38:1.05:2.40; Mw: 5.1 kDa	200 or 400 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Improved dyslipidemia and disorders in glucolipid metabolism, enhanced insulin sensitivity by activating the PI3K/Akt signaling pathway	Increased Allobaculum, Lachnospiraceae_NK4A136_group, Akkermansia, and Bifidobacterium; Increased fecal butyrate level	[243]
Glycyrrhiza uralensis polysaccharide	Composed of galactose, xylose, mannose, and glucose, with a molar ratio of 1:0.22:1.2:0.22	400 mg/kg	High-fat diet-streptozotocin-induced T2DM mice model	Ameliorated hyperglycemia, IR, oxidative stress, enhanced gut barrier function, and reduced liver lipid levels	Increased Akkermansia, Lactobacillus, Romboutsia, and Faecalibaculum, decreased Bacteroides, Escherichia-Shigella, and Clostridium sensu stricto 1	[244]

Notes: T2DM, Type 2 diabetes mellitus; IR, insulin resistance; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; SCFAs, short-chain fatty acids; LPS, lipopolysaccharide; BAs, bile acids; CAT, catalase; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; GLP-1, glucagon-like peptide-1; AMPK, Adenosine 5’-monophosphate (AMP)-activated protein kinase; AKT, protein kinase B; F:B ratio, the ratio of Firmicutes to Bacteroidetes.

5.4.3. Anti-NAFLD

The causal role of gut dysbiosis in NAFLD development has been extensively studied and validated by targeting gut microbiota manipulations. The gut microbial mechanisms of BPs in treating NAFLD involve their interaction with the gut microbiota and subsequent effects on liver health (Table 3 and Figure 3). BPs can act as prebiotics, providing a source of nutrients for beneficial gut bacteria. By promoting the growth of these beneficial microbes, BPs can help restore the balance of the gut microbiota, which is often disrupted in NAFLD. In a previous study, Astragalus polysaccharides (APs) supplementation substantially decreased body weight, fat index, hepatic steatosis, liver triglycerides level, and proinflammatory cytokines expression (IL-1β and IL-6) in the liver and white adipose tissue in HFD-induced mice. It also reduced the expression of FA synthase (FASN) and carnitine palmitoyltransferase-1α (CPT1-α) proteins and the rate-limiting enzymes for de novo synthesis and -oxidation of FAs in HFD-induced mice. In addition, AP intervention significantly enriched the relative abundance of the Desulfovibrio genus, which was negatively correlated with most of the metabolic disorder-related parameters and positively correlated with serum acetic acid level by Spearman’s correlation analysis, suggesting that bacteria in the Desulfovibrio genus were associated with the activity of APs, especially acetic acid production [245]. BPs have been shown to enhance gut barrier integrity. This is important because a compromised gut barrier allows harmful substances, such as bacterial endotoxins, to enter the bloodstream, triggering inflammation and liver damage. By maintaining gut barrier function, BPs help reduce liver inflammation in NAFLD. A study showed AP administration significantly protected against HFD-induced liver injury in rats by attenuating ALT and AST elevation, reduced mild inflammation, micro-vesicular steatosis, and macro-vesicular steatosis in hepatocytes and attenuated hepatic lipid accumulation in NAFLD rats. AP treatment also suppressed hepatic and intestinal proinflammatory gene expression and restored barrier gene expression. Additionally, APs increased the abundance of Bacteroidetes, Proteobacteria, and Episilonbacteria that were positively correlated with HDL-C, LDL-C, TC, and AST but negatively correlated with IL-1β and TNF-α, and decreased the abundance of Firmicutes that was positively correlated with IL-1β and TNF-α [246].

The gut microbiota plays a critical role in the enterohepatic axis. Intestinal barrier disruption is closely linked to gut microbiome dysbiosis, which can result in the translocation of bacteria and their metabolites, especially Gram-negative bacterial LPS can induce systemic inflammation [247]. In contract, SCFAs derived from BPs have been shown to have anti-inflammatory effects, improve insulin sensitivity, and reduce fat accumulation in the liver via the gut-liver axis. These effects can help mitigate the progression of NAFLD. Hepatic lipid accumulation, inflammation, and gut microbiota dysbiosis are hallmarks of NAFLD, which is the leading cause of chronic liver disease. In a previous study, AAP administration reduced the levels of plasma AST, ALT, LDL-C, and TC, and increased HDL-C in NAFLD mice, indicating that liver injury and abnormal lipid metabolism were improved due to the AAP intervention. In addition, liver injury is usually accompanied by inflammation, and AAPs remarkably increased levels of plasma TNF-α and IL-1β. Furthermore, AAPs enriched the abundance of Lactobacillus, Bifidobacterium, Dorea, and Odoribacter which were widely recognized as probiotics to have beneficial effects on host health, and reduced the relative abundances of Allobaculum, Olsenella, Ruminococcus, and Clostridium_XVIII. that were positively correlated with indicators related to the development of NAFLD [248].

BPs can also influence the expression of genes involved in liver fat metabolism. They may upregulate genes responsible for FA oxidation, which promotes the breakdown of accumulated fats in the liver. By enhancing liver fat metabolism, BPs can help reduce fat accumulation and liver steatosis in NAFLD. These gut microbial mechanisms collectively contribute to the potential benefits of BPs in treating NAFLD. By positively influencing gut microbiota composition, gut barrier function, SCFA production, liver fat metabolism, and inflammation, BPs hold promise in managing NAFLD and improving liver health. However, it’s important to note that further research is needed to fully understand and utilize these mechanisms for therapeutic purposes.

Table 3. BPs with therapeutic potential against NAFLD.

Table 3. BPs with therapeutic potential against NAFLD.

Bioactive Polysaccharides	Monosaccharide Composition and Molecular Weight (Mw)	Dosage	Study Approaches	Major Findings	Mode of Action–Gut Microbiota	References
Auricularia auricula polysaccharide	Composed of mannose, glucose, and xylose at a molar ratio of 4.9:2.7:1.1; Mw: 1670 kDa	200 mg/kg	High-fat and high-cholesterol diet-induced NAFLD mice model	Improved liver injury and abnormal lipid metabolism	Reduced Allobaculum, Olsenella, Ruminococcus, and Clostridium_XVIII and enriched Lactobacillus, Bifidobacterium, Dorea, and Odoribacter; Increased deoxycholic acid (DCA)	[248]
Astragalus membranaceus polysaccharide	Composed of rhamnose (1.6%), arabinose (23.39%), xylose (0.84%), glucose (70.55%), and galactose (3.61%)	4% in HFD	High-fat diet-induced mice model	Suppressed hepatic fatty acid synthase (FASN) and CD36 protein expression	Enriched Desulfovibrio genus that produced acetic acid	[249]
Astragalus membranaceus polysaccharide	Composed of glucose (84.86%), arabinose (4.49%), galactose (3.92%) and ribose (3.26%)	200 mg/kg	High-fat diet-induced NAFLD rat model	Decreased body weight; Prevented Liver injury; Improved IR Attenuated hepatic lipid accumulation	Decreased the F/B ratio; Increased Proteobacteria and Epsilonbacteria; little effect on the profile of fecal SCFAs, decreased GPR 41 and 43 gene expression	[250]
Auricularia cornea var. Li. polysaccharides	Mw: > 7 kD	200 mg/kg	High-fat diet-induced NAFLD rat model	Lowered HOMA-IR, body fat rate, liver index, and body weight gain; decrease in hepatic levels of TC, and TG; alleviated hepatic oxidative stress	Decreased the F/B ratio; Increased Bifidobacterium, Bacteroides, Odoribacter, Alloprevotella, Rikenellaceae RC9 gut group and Blautia; Decreased Parabacteroides and Lachnoclostridium	[178]
Lycium barbarum polysaccharide	Composed of mannose, rhamnose, glucose, galactose, and arabinose with a mole ratio of 1.00: 0.93: 12.55: 0.31: 0.53	50 mg/kg	High-fat diet-induced NAFLD rat model	Restore the intestinal tight junctions; inhibit hepatic inflammatory factors	Decreased the F/B ratio; Increased gut microbial diversity; Decreased intestinal LPS level	[251]
Laminaria japonica polysaccharide	Composed of fucose (40.6%), rhamnose (1.4%), arabinose (2.0%), galactose (27.3%), and mannose (26.7%); Mw: 200 kDa	5% in diet	High-fat diet-induced NAFLD mice model	Attenuated obesity-related features; attenuated liver steatosis and hepatocellular ballooning	Reduced F/B ratio; Elevated propionate-producing bacteria Bacteroides and Akkermansia; Increased fecal propionate level	[252]
Ganoderma lucidum polysaccharide	Mw: >5 kDa	38 mg/kg	High-fat and high-fructose diet-induced NAFLD mice model	Inhibited the excessive exaltation of body weight, glucose tolerance, fasting blood glucose and lipid levels, hepatic TC, TG levels	Increased Aerococcus, Weissella, Corynebacterium_1, decreased Romboutsia, [Ruminococcus]_torques_group; Enriched microbial nicotinate and nicotinamide metabolism and peptidoglycan biosynthesis	[253]
Ganoderma lucidum polysaccharide	Composed of 12-hydroxyganoderic acid, ganoderic acid, ganoderic acid, poricoic acid, and ganoderic acid	150 mg/kg	High-fat and high-fructose diet-induced NAFLD rat model	Alleviated dyslipidemia through decreasing the levels of serum TG, TC, and LDL-C, and inhibiting hepatic lipid accumulation and steatosis	Reduced F/B ratio; Promoted Alloprevotella, Prevotella, Alistipes; Decreased Anaerotruncus, Dorea, Barnesiella, Methanosphaera; Increased fecal BAs and SCFAs levels	[195]
Lentinan	β-glucan	500 mg/kg in the diet	High-fat diet-induced NAFLD mice model	Improved gut microbiota dysbiosis; improved intestinal barrier integrity	Increased gut microbial diversity; Reduced F/B ratio; Enhanced Bifidobacterium Streptococcus, and Enterococcus; Reduced serum LPS level	[254]
Aureobasidium pullulans strain AFO-202 β-glucan	β-glucan	1 mg/kg	High-fat diet-induced NASH mice model	Decreased inflammation associated hepatic cell ballooning and steatosis	Reduced F/B ratio; Increased Lactobacillus, Turicibacter, and Bilophila; Increased fecal succinic acid level	[255]
Ophiopogon japonicus polysaccharide	Composed of Fruf (2 → 1), and a side chain of Fruf (2 → 6) Fruf (2→) per average 2.8 of main chain residues; Mw: 3400 Da	0.5% in diet	High-fat diet-induced NAFLD mice model	Ameliorated lipid accumulation, liver steatosis, and chronic inflammation	Increased Akkermansia muciniphila	[256]
Lonicerae flos polysaccharides	-	100 and 200 mg/kg	High-fat and high-fructose diet-induced NAFLD mice model	Regulated glucose metabolism dysregulation, IR, lipid accumulation, inflammation, fibrosis, and autophagy by activating the AMPK signaling pathway	Increased Muribaculum and Desulfovibrio	[257]
Salviae miltiorrhizae Radix et Rhizoma polysaccharide	Composed of galacturonic acid, arabinose, galactose, rhamnose, and glucose, with molar ratios of 17.9:1.3:1.7:1.2:1; Mw: 32.6 kDa	10 and 20 mg/kg	High-fat-induced NAFLD mice model	Attenuated hepatocellular steatosis, hepatic fibrosis, and inflammation; Improved gut barrier function	Increased Bifidobacterium pseudolongum, Ruminococcus gnavus, Clostridium celatum, Clostridium cocleatum	[258]
Ostrea rivularis polysaccharide	Composed of galactose and glucose in a molar percent of 23.7% and 76.3%, respectively; Mw: 118 kDa	100 and 400 mg/kg	High-fat-induced NAFLD ApoE−/− mice model	Reduced TC, TG, and LDL-C levels, and increased HDL level in serum; Enhanced intestinal barrier function	Reduced F/B ratio; Reduced Firmicutes and Proteobacteria	[259]
Smilax china L. polysaccharide	Composed of arabinose, galactose, glucose, xylose, galacturonic acid, with molar ratios of 2.47:7.17:34.62:10.82:1.38; Mw: 134 kDa	100, 200, and 400 mg/kg	High-fat-induced NAFLD mice model	Improved dyslipidemia, decreased depositions of liver lipids and adipose tissues, regulated hepatic fat metabolism	Reduced F/B ratio; Increased Rikenellaceae_RC9_gut_group, Muribaculaceae, and Lachnospiraceae_NK4A136_group, and decreased Coriobacteriaceae_UCG-002, Faecalibaculum, and Allobaculum	[260]
Tegillarca granosa polysaccharide	Composed of mannose, glucosamine, rhamnose, glucuronic acid, galactosamine, glucose, galactose, xylose, fucose, with molar ratios of 1:1.38:0.87:0.53:0.52:5.37:1.38:1.05:2.40; Mw: 5.1 kDa	200 and 400 mg/kg	High-fat-induced NAFLD mice model	Reduced excessive hepatic lipid accumulation, dyslipidemia, abnormal liver function, and steatosis	Increased fecal SCFAs-producing bacteria (Lactobacillus, Dubosiella, and Akkermansia); Increased cecal SCFAs level	[261]
Panacis japonici rhizome polysaccharide	Composed of glucose (74 .99 5%), galactose (17.054%), and arabinose (7.949%); Mw: 167.178 kDa	25 and 100 mg/kg	High-fat-induced NAFLD mice model	Reduced liver fat accumulation, blood lipids, and ALT	Reduced F/B ratio; Decreased Turicibacter, Dubosiella, and Staphylococcus, and increased Bacteroides, Blautia, and Lactobacillus; Decreased fecal acetate and propionate level	[262]
Fufang Zhenzhu Tiaozhi polysaccharide	Composed of fucose (0.77%), arabinose (30.38%), galactose (24.43%), glucose (26.74%), xylose (3.23%), mannose (4.55%), galacturonic acid (9.37%), and glucuronic acid (0.52%)	100 and 300 mg/kg	High-fat-induced NASH mice model	Improved liver lipid metabolism, reduced inflammation, and fibrosis, improved intestinal barrier function	Decreased Gammaproteobacteria, Clostridium, and Coprococcus, and increased Dehalobacteraceae and Dehalobacterium	[263]

Notes: NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; IR, insulin resistance; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; AMPK, adenosine 5’-monophosphate (AMP)-activated protein kinase; ALT, alanine aminotransferase; SCFAs, short-chain fatty acids; LPS, lipopolysaccharide; F:B ratio, the ratio of Firmicutes to Bacteroidetes.

5.4.4. Anti-CVD

The gut microbial mechanisms of BPs in treating CVD involve their interaction with the gut microbiota and subsequent effects on various risk factors associated with CVD (Table 4 and Figure 3). Here are some of the key mechanisms: BPs can act as prebiotics, providing a source of nutrients for beneficial gut bacteria. By promoting the growth of these beneficial microbes, BPs can help restore the balance of the gut microbiota, which is closely linked to CVD risk factors such as inflammation, lipid metabolism, and blood pressure regulation. Auricularia auricula polysaccharide and Tremella polysaccharide could reduce gut microbial F/B ratio and increase Lactobacillus, Rumincococcacea, and Muribaculaceae and decrease Allobaculum, Corynebacterium, Blautia, and Turicibucter to inhibit the development of hyperlipidemia in HFD-induced hyperlipidemia rat model [264]. Fermentation of BPs by gut bacteria can result in the production of SCFAs, which have been shown to have various cardiovascular benefits, including anti-inflammatory effects, improvement of lipid metabolism, and regulation of blood pressure. Dysbiosis of gut microbiota can increase TMAO production, ultimately contributing to CVD [110]. Studies showed that Ganoderma lucidum spore polysaccharides could reduce serum TMAO levels and enhance heart function [265]. BPs can affect lipid metabolism by influencing the expression of genes involved in cholesterol synthesis, lipoprotein metabolism, and BA recycling. By modulating lipid metabolism, BPs may help reduce the buildup of cholesterol in the arteries and improve lipid profiles, lowering the risk of CVD. Chronic inflammation is a crucial factor in the development and progression of CVD. BPs with anti-inflammatory properties can help reduce inflammation by inhibiting the production of pro-inflammatory cytokines and modulating immune responses within the gut and systemically. Some BPs have been found to enhance NO production in the body. NO is a signaling molecule involved in the regulation of blood vessel function, including promoting vasodilation and reducing vascular inflammation. Cuminum cyminum polysaccharides have been observed to enhance phagocytosis and stimulate the production of NO and various cytokines such as interleukins (ILs), TNF-α, and interferons (IFNs), which are important for regulating inflammation and immune responses [160]. By enhancing NO production, BPs may help improve endothelial function and blood flow, reducing the risk of CVD.

These gut microbial mechanisms collectively contribute to the potential benefits of BPs in treating or preventing CVD. By positively influencing gut microbiota composition, SCFA production, lipid metabolism, inflammation, and NO production, BPs hold promise in improving cardiovascular health. However, it’s important to note that further research is needed to fully understand and utilize these mechanisms for therapeutic purposes. It is always recommended to consult with healthcare professionals for proper management and prevention of CVD.

Table 4. BPs with therapeutic potential against CVD.

Table 4. BPs with therapeutic potential against CVD.

Bioactive Polysaccharides	Monosaccharide Composition and Molecular Weight (Mw)	Dosage	Study Approaches	Major Findings	Mode of Action–Gut Microbiota	References
Lycium barbarum polysaccharide	-	100 mg/kg	High-fat diet-induced myocardial injury mice model	Improved left ventricular function and serum trimethylamine N-oxide; Reduced intestinal permeability and inflammation and alleviated myocardial injury	Increased Bifidobacterium, Lactobacillus, and Romboutsia; decreased the Gordonibacter, Parabacteroides, and Anaerostipes; Increased tryptophan metabolites	[266]
Cipangopaludina chinensis polysaccharide	Composed of glucose (95.2%), rhamnose (4.2%) and fucose (0.6%)	100 and 400 mg/kg	High-fat diet-induced atherosclerosis ApoE−/− mice model	Regulating plasma lipids balance, decreasing atherosclerotic index, and reducing atherosclerotic plaque area	Reduced F/B ratio; Increased Lactobacillus, Pediococcus, Ruminiclostridium, Alloprevotella and Flavobacterium	[267]
Chenopodium quinoa Willd. polysaccharides	Composed of glucose and arabinose, with a mole ratio of 1.17:1; Mw: 82.7 kDa	300 and 600 mg/kg	High-fat diet-induced hyperlipidemia rat model	Decreased serum TG, LDL-C, MDA, ALT, and AST levels and reduced hepatic lipid accumulation	Reduced F/B ratio; Increased Ruminiclostridium and decreased Desulfovibrio and Allobaculum	[268]
Ginger polysaccharides	-	50, 100 and 200 mg/kg	High-fat diet-induced hyperlipidemia rat model	Decreased blood lipid, serum inflammatory markers, and enhanced antioxidant capacity	Reduced F/B ratio; Increased the growth of Akkermansia muciniphila	[269]
Auricularia auricula polysaccharide (AAP) and Tremella polysaccharide (TP)	AAP composed of glucose (59.19%), galactose (22.63%) mannose (7.76%), fucose (6.46%), xylose (3.97%) and glucuronic acid (3.46%); TP was mainly composed of glucose (19.62%), mannose (36.18%), fucose (22.25%), xylose (18.62%) and glucuronic acid (3.33%); Mw: > 8 kDa	100 mg/kg AAP + 100 mg/kg TP	High-fat diet-induced hyperlipidemia rat model	Inhibited the development of hyperlipidemia and reduced lipid levels and fat accumulation; improved intestinal barrier function	Reduced F/B ratio; Increased Lactobacillus, Rumincococcacea, and Muribaculaceae; Decreased Allobaculum, Corynebacterium, Blautia, and Turicibucter	[264]
Grifola frondose polysaccharide	Composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and fucose with molar ratio of 25.49: 5.18: 9.49 :7.30: 27.59: 15.02: 9.92; Mw: 15850 kDa, 280.7 kDa and 18.18 kDa	200 and 900 mg/kg	High-fat diet-streptozotocin-induced diabetes mice model	Reduced serum levels of TC, TG, and LDL-C; enhanced hepatic BAs synthesis and excretion	Elevated Alistipes and reduced Streptococcus, Enterococcus, Staphylococcus and Aerococcus	[270]
Walnut green husk polysaccharide	Composed of glucuronic acid, arabinose, and galactose; Mw: 4813 Da	200, 400 and 800 mg/kg	High-fat diet-induced obesity mice model	Improved hepatic steatosis and vascular endothelial dysfunction	Increased Akkermansia, Lachnoclostridium and norank_f__Muribaculaceae and decreased Prevotellaceae_UCG-001, Helicobacter, Alloprevotella and Allobaculum	[271]
Ganoderma lucidum spore polysaccharide	Composed of mannose (1.00%), glucose (42.17%), galactose (4.78%), and fucose (1.75%); Mw: >10 kDa (72.93%) and >20 kDa (52.74%)	50 mg/kg	TMAO-induced cardiac dysfunction rat model	Reduced serum TMAO, TC, TG, and LDL-C levels; increased heart function	Increased Firmicutes and Proteobacteria and reduced Actinobacteria and Tenericutes	[265]

Notes: CVD, cardiovascular diseases; TG, triglyceride; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; MDA, malondialdehyde; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BAs, bile acids; SCFAs, short-chain fatty acids; TMAO, trimethylamine oxide; F:B ratio, the ratio of Firmicutes to Bacteroidetes.

6. Conclusions and Future Perspectives

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