Saccharina Japonica Polysaccharides Suppress High-Fat Diet-Induced Obesity and Modulate Gut Microbiota Composition and Function.

Recent studies have highlighted the potential of Saccharina japonica Polysaccharides (SJPs) in alleviating high-fat diet (HFD)-induced obesity by regulating gut microbiota, which warrants further exploration to elucidate the underlying structure-activity relationship. In this study, five polysaccharide fractions (Sj-T, Sj-T-1, Sj-T-2, Sj-T-3, and Sj-T-4) with different structure characteristics were prepared from S. japonica, and their effects on HFD-induced obesity and gut microbiota composition were investigated using C57BL/6J mice. The results revealed that oral administration of Sj-T considerably suppressed HFD-induced obesity, glucose metabolic dysfunction, and other disordered symptoms. While, Sj-T-2, which has the lowest molecular weight, was the most effective in alleviating HFD-induced obesity and had the second-best effect on improving HFD-induced impaired glucose tolerance among the five SJPs. Supplementation with SJPs significantly modulated HFD-induced gut microbiota dysbiosis both at the phylum and species levels, such as enriching Desulfobacterota and Actinobacteriota, while suppressing the abundance of Bacteroidota. Sj-T also dramatically restored the gut microbiota composition by modulating the abundance of many crucial gut bacterial taxa, including s_Bacteroides_acidifaciens, s_Lachnospiraceae _bacterium, and g_Lachnospiraceae_NK4A136_group. Besides, SJPs also dramatically altered the function of gut microbiota, including many carbohydrate-metabolism enzymes. This study highlights the potential of SJPs in preventing obesity and restoring intestinal homeostasis in obese individuals.

Metagenomic Insights into the Anti-Obesity Effect of a Polysaccharide from Saccharina japonica.

Saccharina japonica polysaccharides exhibit great potential to be developed as anti-obesity and prebiotic health products, but the underlying mechanism has not been adequately addressed. In this study, we investigated the potential mechanism of a S. japonica polysaccharide fraction (SjC) in preventing high-fat-diet (HFD)-induced obesity in mice using 16S rRNA gene and shotgun metagenomic sequencing analysis. SjC was characterized as a 756 kDa sulfated polysaccharide and 16 weeks of SjC supplementation significantly alleviated HFD-induced obesity, insulin resistance, and glucose metabolism disorders. The 16S rRNA and metagenomic sequencing analysis demonstrated that SjC supplementation prevented gut microbiota dysbiosis mainly by regulating the relative abundance of Desulfovibrio and Akkermansia. Metagenomic functional profiling demonstrated that SjC treatment predominantly suppressed the amino acid metabolism of gut microbiota. Linking of 16S rRNA genes with metagenome-assembled genomes indicated that SjC enriched at least 22 gut bacterial species with fucoidan-degrading potential including Desulfovibrio and Akkermansia, which showed significant correlations with bodyweight. In conclusion, our results suggest that SjC exhibits a promising potential as an anti-obesity health product and the interaction between SjC and fucoidan-degrading bacteria may be associated with its anti-obesity effect.

Saccharina japonica fucan suppresses high fat diet-induced obesity and enriches fucoidan-degrading gut bacteria.

Low molecular weight seaweed polysaccharides exhibit promising potential as novel therapeutics for the prevention of obesity and gut microbiota dysbiosis. The interplay between polysaccharides and gut microbiota may play crucial roles in their anti-obesity effects, but is largely unknown, including the impact of polysaccharides on the composition of the gut microbiota with polysaccharide-degrading capacity. The primary structure of a 5.1 kDa fucan (J2H) from Saccharina japonica was characterized and oral administration of J2H effectively suppressed high-fat diet-induced obesity, blood glucose metabolic dysfunction, dyslipidemia, and gut microbiota dysbiosis. Furthermore, the Jensen-Shannon divergence analysis demonstrated that J2H enriched at least four gut bacterial species with fucoidan-degrading potential, including Bacteroides sartorii and Bacteroides acidifaciens. Our findings suggest that the low molecular weight S. japonica fucan, J2H, is a promising potential agent for obesity prevention and its enrichment of gut bacteria with fucoidan-degrading potential may play a vital role in the anti-obesity effects.

Composition-Activity Relationships of Polysaccharides from Saccharina japonica in Regulating Gut Microbiota in Short-Term High-Fat Diet-Fed Mice.

Saccharina japonica polysaccharide could modulate gut microbiota composition; however, the composition-activity relationship remains unclear, thus restricting its application. In the current study, we investigated the impact of eight different S. japonica polysaccharide fractions on the gut microbiota after day 2 and day 14 treatments on high-fat diet (HFD) feeding mice. The results showed that a 2 day HFD dramatically altered gut microbiota composition, and the additional 12 day HFD further strengthened the gut microbiota dysbiosis in the HFD group. LjA-1 and LjA-3 could partially alleviate the dysbiosis of gut microbiota composition and significantly alter gut microbiota function. Multiple linear regression analysis revealed that the sulfate content and the molecular weight distributions were the main factors affecting the dominant gut bacterial genera. Our findings reveal that gut microbiota homeostasis could be disordered by HFD at day 2 and provide insights into the quantitative composition-activity relationships of polysaccharides in regulating gut microbiota.

Comparative Study of Sargassum fusiforme Polysaccharides in Regulating Cecal and Fecal Microbiota of High-Fat Diet-Fed Mice.

Seaweed polysaccharides represent a kind of novel gut microbiota regulator. The advantages and disadvantages of using cecal and fecal microbiota to represent gut microbiota have been discussed, but the regulatory effects of seaweed polysaccharides on cecal and fecal microbiota, which would benefit the study of seaweed polysaccharide-based gut microbiota regulator, have not been compared. Here, the effects of two Sargassum fusiforme polysaccharides prepared by water extraction (SfW) and acid extraction (SfA) on the cecal and fecal microbiota of high-fat diet (HFD) fed mice were investigated by 16S rRNA gene sequencing. The results indicated that 16 weeks of HFD dramatically impaired the homeostasis of both the cecal and fecal microbiota, including the dominant phyla Bacteroidetes and Actinobacteria, and genera Coriobacteriaceae, S24-7, and Ruminococcus, but did not affect the relative abundance of Firmicutes, Clostridiales, Oscillospira, and Ruminococcaceae in cecal microbiota and the Simpson's index of fecal microbiota. Co-treatments with SfW and SfA exacerbated body weight gain and partially reversed HFD-induced alterations of Clostridiales and Ruminococcaceae. Moreover, the administration of SfW and SfA also altered the abundance of genes encoding monosaccharide-transporting ATPase, α-galactosidase, ß-fructofuranosidase, and ß-glucosidase with the latter showing more significant potency. Our findings revealed the difference of cecal and fecal microbiota in HFD-fed mice and demonstrated that SfW and SfA could more significantly regulate the cecal microbiota and lay important foundations for the study of seaweed polysaccharide-based gut microbiota regulators.

Characterization and hypoglycemic effects of sulfated polysaccharides derived from brown seaweed Undaria pinnatifida.

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.

Gut microbiota-mediated xanthine metabolism is associated with resistance to high-fat diet-induced obesity.

Resistance to high-fat diet-induced obesity (DIR) has been observed in mice fed a high-fat diet and may provide a potential approach for anti-obesity drug discovery. However, the metabolic status, gut microbiota composition, and its associations with DIR are still unclear. Here, ultraperformance liquid chromatography-tandem mass spectrometry-based urinary metabolomic and 16S rRNA gene sequencing-based fecal microbiome analyses were conducted to investigate the relationship between metabolic profile, gut microbiota composition, and body weight of C57BL/6J mice on chow or a high-fat diet for 8 weeks. PICRUSt analysis of 16S rRNA gene sequences predicted the functional metagenomes of gut bacteria. The results demonstrated that feeding a high-fat diet increased body weight and fasting blood glucose of high-fat diet-induced obesity (DIO) mice and altered the host-microbial co-metabolism and gut microbiota composition. In DIR mice, high-fat diet did not increase body weight while fasting blood glucose was increased significantly compared to chow fed mice. In DIR mice, the urinary metabolic pattern was shifted to a distinct direction compared to DIO mice, which was mainly contributed by xanthine. Moreover, high-fat diet caused gut microbiota dysbiosis in both DIO and DIR mice, but in DIR mice, the abundance of Bifidobacteriaceae, Roseburia, and Escherichia was not affected compared to mice fed a chow diet, which played an important role in the pathway coverage of FormylTHF biosynthesis I. Meanwhile, xanthine and pathway coverage of FormylTHF biosynthesis I showed significant positive correlations with mouse body weight. These findings suggest that gut microbiota-mediated xanthine metabolism correlates with resistance to high-fat DIO.

Sargassum fusiforme Polysaccharides Prevent High-Fat Diet-Induced Early Fasting Hypoglycemia and Regulate the Gut Microbiota Composition.

A low fasting blood glucose level is a common symptom in diabetes patients and can be induced by high-fat diet (HFD) feeding at an early stage, which may play important roles in the development of diabetes, but has received little attention. In this study, five polysaccharides were prepared from Sargassumfusiforme and their effects on HFD-induced fasting hypoglycemia and gut microbiota dysbiosis were investigated. The results indicated that C57BL/6J male mice fed an HFD for 4 weeks developed severe hypoglycemia and four Sargassumfusiforme polysaccharides (SFPs), consisting of Sf-2, Sf-3, Sf-3-1, and Sf-A, significantly prevented early fasting hypoglycemia without inducing hyperglycemia. Sf-1 and Sf-A could also significantly prevent HFD-induced weight gain. Sf-2, Sf-3, Sf-3-1, and Sf-A mainly attenuated the HFD-induced decrease in Bacteroidetes, and all five SFPs had a considerable influence on the relative abundance of Oscillospira, Mucispirillum, and Clostridiales. Correlation analysis revealed that the fasting blood glucose level was associated with the relative abundance of Mucispinllum and Oscillospira. Receiver operating characteristic analysis indicated that Mucispinllum and Oscillospira exhibited good discriminatory power (AUC = 0.745-0.833) in the prediction of fasting hypoglycemia. Our findings highlight the novel application of SFPs (especially Sf-A) in glucose homeostasis and the potential roles of Mucispinllum and Oscillospira in the biological activity of SFPs.

Structural Characterization and α-Glucosidase Inhibitory and Antioxidant Activities of Fucoidans Extracted from Saccharina japonica.

Two sulfated fucoidan fractions (Lj3 and Lj5) were extracted from Saccharina japonica and then subjected to acid hydrolysis to obtain Lj3h and Lj5h. Lj3h and Lj5h were characterized using IR, methylation analysis, and mass spectrometry. It was found that Lj3h and Lj5h were homogeneous low molecular weight fucoidans. Specifically, Lj3h was composed of the main chain of 1,3-linked α-L-fucopyranose residues with sulfate at C-2 and/or C-4 and three different monosaccharides (galactose, glucose, mannose) branched at C-2 and/or C-4 of fucose residue. Lj5h contained backbones of alternating galactopyranose residues and fucopyranose residues attached via a 1→3 linkage (galactofucan) and 1→6 linked galactan. The sulfation pattern was mainly located at C2/C4 fucose or galactose residues and more branches occupied at C-4 of fucose residue and C-2, C-3 or/and C-6 of galactose residue. In vitro assay indicated that, among the four fucoidans tested, only Lj5 showed potent α-glucosidase inhibitory activity with IC50 of 153.27±22.89 µg/mL, and the two parent fucoidans, Lj3 and Lj5, showed better antioxidant activity than their derivatives. These findings highlight the structure and bioactivity diversity of Saccharina japonica-derived fucoidans.

The Antioxidant Activity of Polysaccharides Derived from Marine Organisms: An Overview.

Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes the sources, chemical composition, structural characteristics, and antioxidant capacity of marine antioxidant polysaccharides, as well as their protective in vivo effects mediated by antioxidative stress reported in the last few years (2013-2019), and especially highlights the dominant role of marine algae as antioxidant polysaccharide source. In addition, the relationships between the chemical composition and structural characteristics of marine antioxidant polysaccharides with their antioxidant capacity were also discussed. The antioxidant activity was found to be determined by multiple factors, including molecular weight, monosaccharide composition, sulfate position and its degree.