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Revisit the effects of fucoidan on gut microbiota in health and disease: What do we know and what do we need to know?
Abstract
Fucoidan is a highly sulfated polysaccharide which is mainly isolated from marine brown seaweeds. During the past decades, fucoidan has been the focus of intense research due to its multifunctional properties and profound clinical significance. Today, oral preparations of fucoidan are widely used as therapeutic drugs and dietary supplements in China, Australia, Russia, South Korea and Japan. Accumulating evidence indicates that dietary fucoidan is not absorbed in the upper gastrointestinal tract. Therefore, when reaching the distal colon, fucoidan would exert a significant effect on gut microbiota. Previous studies have illustrated a remarkable array of beneficial impacts of fucoidan on gut microbiota, however, still we are at the beginning of this research field. In this review article, I revisit the effects of fucoidan on gut microbiota in health and disease and highlight that future studies need to focus on deciphering the structure-activity relationship of fucoidan as a potential prebiotic and demonstrating a causal role of gut microbiota in the treatment of diseases by fucoidan and its associated derivatives.
... Fucoidan's structure differs significantly depending on its source, particularly among different species of brown algae. Broadly, fucoidans have been classified into two structural types: Type I, which consists of 1,3-α-L-Fucp units with sulfate groups at the O-2 and O-4 positions, and Type II, which features alternating 1,3-and 1,4-α-L-Fucp units with sulfate groups at the O-2, O-3, and O-4 positions [107]. Recent studies have uncovered additional structural variations, including different sulfate substitution patterns, molecular weights, branching configurations, and polysaccharide residues, although they generally retain a backbone like Type I and Type II fucoidans [108]. ...
Fucoidan, a sulfated polysaccharide found primarily in brown algae, is known for exhibiting various biological activities, many of which have been attributed to its sulfate content. However, recent advancements in techniques for analyzing polysaccharide structures have highlighted that not only the sulfate groups but also the composition, molecular weight, and structures of the polysaccharides and their monomers play a crucial role in modulating biological effects. This review comprehensively provides the monosaccharide composition, degree of sulfation, molecular weight distribution, and linkage of glycosidic bonds of fucoidan, focusing on the diversity of its biological activities based on various characteristics. The implications of these findings for future applications and potential therapeutic uses of fucoidan are also discussed.
... The size of fucoidans has not been studied. Previous studies have shown that fucoidan with a molecular weight of 310-1614 kD increased the abundance of probiotic bacteria Lactobacillus and Akkermentia and decreased the pathogenic bacteria, Peptococcus, Helicobacter rodentium, Mucispirillum schaedleri, Rikenellaceae, and Alistipes [64]. The results were partially consistent with the present study. ...
Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer’s disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and λ-carrageenan would improve memory impairment in Alzheimer’s disease-induced rats caused by an infusion of toxic amyloid-β(Aβ). Fucoidan and λ-carrageenan were dissected into low-MW by Luteolibacter algae and Pseudoalteromonas carrageenovora. Rats receiving an Aβ(25–35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW λ-carrageenan (AD-C-H), and 1% low-MW λ-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3®pAkt®pGSK-3β pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating.
... Ma et al. [65] observed that a HFD significantly decreased Lachnospiraceae_NK4A136_group, which is a butyrate producer. In addition, Shang et al. [66] showed that fucoidan regulated the gut microbiota and ameliorated intestinal dysbiosis by increasing the abundance of Clostridiales_vadinBB60_group in mice with metabolic syndrome. Contrary to our expectations, HFD significantly reduced Oscillibacter in the study. ...
In this study, we annotated the major flavonoid glycoside, rutin, of djulis hull crude extract using a Global Natural Products Social Molecular Networking (GNPS) library and its MS/MS spectra. To evaluate the protective effect of djulis hull crude extract and rutin on glucose tolerance, we fed mice a high-fat diet (HFD) for 16 weeks to induce hyperglycaemia. These results showed that crude extract significantly decreased HFD-induced elevation in the area under the curve (AUC) of weekly random blood glucose and oral glucose tolerance tests (OGTT), homeostasis model assessment (HOMA-IR), and advanced glycation end product (AGE) levels, and significantly increased pIRS1 and Glut4 protein expression in epididymal white adipose tissue (eWAT) and liver. Furthermore, the HFD-induced reduction in the activity of glutathione peroxidase (GPx) and catalase (CAT) was reversed by crude extract. In addition, ZO-1 and occludin protein expression in the colon was markedly downregulated in HFD-fed mice, resulting in decreased intestinal permeability and lipopolysaccharide (LPS) translocation, but were restored following crude extract. Moreover, the crude extract intervention had a profound effect on the alpha diversity and microbial community in the gut microbiota. Therefore, djulis hull crude extract could improve blood glucose and increase insulin receptor sensitivity in HFD-induced hyperglycaemia, which is likely due to its modulation of the gut microbiota, preservation of the integrity of the intestinal barrier to reduce body inflammation, increased antioxidant activity, and modulation of insulin signalling.
... The structure of fucoidan (reproduced from Shang, 2020[48]). ...
Fucoidans are cell wall polysaccharides found in various species of brown seaweeds. They are fucose-containing sulfated polysaccharides (FCSPs) and comprise 5-20% of the algal dry weight. Fucoidans possess multiple bioactivities, including antioxidant, anticoagulant, antithrombotic, anti-inflammatory, antiviral, anti-lipidemic, anti-metastatic, anti-diabetic and anti-cancer effects. Dietary fucoidans provide small but constant amounts of FCSPs to the intestinal tract, which can reorganize the composition of commensal microbiota altered by FCSPs, and consequently control inflammation symptoms in the intestine. Although the bioactivities of fucoidans have been well described, there is limited evidence to implicate their effect on gut microbiota and bowel health. In this review, we summarize the recent studies that introduce the fundamental characteristics of various kinds of fucoidans and discuss their potential in altering commensal microorganisms and influencing intestinal diseases.
... Moreover the most promising anticancer drug isolated from brown algae is the sulfated polysaccharide fucoidan. It is reported to have effective anticancer activity against various types of cancer (Shang, 2020). Fucoidans are sulfated homo-and heteropolysaccharides, mainly composed of α-L-fucopyranose residues, which may be partially sulfated and/or acetylated. ...
Cancer has been listed as one of the world’s five incurable diseases by the World Health Organization and causes tens of thousands of deaths every year. Unfortunately, anticancer agents either show limited efficacy or show serious side effects. The algae possess high nutritional value and their polysaccharides have a variety of biological activities, especially anti-cancer and immunomodulatory properties. Algal polysaccharides exert anti-cancer effects by inducing apoptosis, cell cycle arrest, anti-angiogenesis, and regulating intestinal flora and immune function. Algal polysaccharides can be combined with nanoparticles and other drugs to reduce the side effects caused by chemotherapy and increase the anticancer effects. This review shows the signal pathways related to the anti-cancer mechanisms of algal polysaccharides, including their influence on intestinal flora and immune regulation, the application of nanoparticles, and the effects on combination therapy and clinical trials of cancer treatments.
... Methylated, acetylated, and persulphated fucoidan derivatives can also significantly enhance biological functional properties. Due to its structural complexity, fucoidan has studied in a variety of experimental models and in all kind of biological activities such as anti-tumour, antioxidant, anti-coagulation, anti-thrombotic, anticancer, anti-viral, anti-inflammatory, gastric protective, regulates gut microbiota metabolism, and anti-diabetic effects, as well as intestinal disease treatment (Dai, Jiang, Lee, Jeon, & Kang, 2019;Lim, Aida, Maskat, Latip, & Badri, 2016;Liu et al., 2020;Marinval et al., 2018;Shang, 2020;Wang, Xing, et al., 2019;Xu et al., 2018). Moreover, previous experimental results have indicated that fucoidan has hypoglycaemic effectiveness and can prevent complications related to diabetes mellitus (Kim, Rioux, & Turgeon, 2015;Mabate, Daub, Malgas, Edkins, & Pletschke, 2021;Shan et al., 2016;Zhao et al., 2020). ...
Background
Diabetes mellitus is an endocrine and metabolic system disease characterized by hyperglycaemia and insulin resistance, and has become a prevalent disease around the world. Fucoidan has a good hypoglycaemic effect and ideal development potential in the treatment of diabetes based on their specific chemical structures, such as monosaccharide compositions and glycosidic linkages.
Scope and approach
However, the relationship between structure-function and activity has not yet been clarified. This article discusses the structural characteristics of fucoidan, including its backbone structure, glycosidic bond positions, monosaccharide types, sulphate content, and molecular weight. The potential therapeutic effect of fucoidan on hyperglycaemia and diabetic complications caused by diabetes is also reviewed.
Key findings and conclusions
Fucoidan reduces blood sugar levels through α-amylase and α-d-glucosidase inhibition, a Sirt-1-dependent manner, and the cAMP, PI3K/AKT, and JNK/AKT signalling pathways. The outstanding biological function of fucoidan is due its unique chemical structure. Among them, fucoidan of low molecular weight and high degree of sulfation displays greater anti-diabetic activity, and persulphated fucoidan derivatives showed significantly enhanced hypoglycaemic activities. Moreover, only (1,3) and (1,4) alternatively linked fucoidan showed a stronger inhibitory effect on α-d-glucosidase.
Non-alcoholic steatohepatitis (NASH) is one of the most chronic and incurable liver diseases triggered mainly by an inappropriate diet and hereditary factors which burden liver metabolic stress, and may result in liver fibrosis or even cancer. While the available drugs show adverse side effects. The non-toxic bioactive molecules derived from natural resources, particularly marine algal polysaccharides (MAPs), present significant potential for treating NASH. In this review, we summarized the protective effects of MAPs on NASH from multiple perspectives, including reducing oxidative stress, regulating lipid metabolism, enhancing immune function, preventing fibrosis, and providing cell protection. Furthermore, the mechanisms of MAPs in treating NASH were comprehensively described. Additionally, we highlight the influences of the special structures of MAPs on their bioactive differences. Through this comprehensive review, we aim to further elucidate the molecular mechanisms of MAPs in NASH and inspire insights for deeper research on the functional food and clinical applications of MAPs.
Marine sulfated polysaccharides (SPs) have been widely used as food stabilisers or gelling agents. Recently, accumulated evidence has been collected regarding their bioactivities, including anticoagulant, antiviral and immunoregulatory activities. This review compares the structural characteristics of SPs from algae, marine animals and marine microorganisms. Their functional and biological activities and mechanisms involved are extensively summarised. The influences of the sulfate groups of SPs on their functional/bioactive properties are also highlighted. This overview aims to provide a deep understanding of marine SPs to facilitate their industrial applications in the food, cosmetic and pharmaceutical areas.
Marine algae contain abundant polysaccharides that support a range of health-promoting activities; however, the high molecular weight, high viscosity, and low solubility of marine algae polysaccharides (MAPs) limit their application in food, agriculture and medicine. Thus, as the degradation products of MAPs, marine algae oligosaccharides (MAOs) have drawn increasing attention. Most MAOs are non-digestible by digestive enzyme in the human gastrointestinal tract, but are fermented by bacteria in the gut and converted into short-chain fatty acids (SCFAs). MAOs can selectively enhance the activities of some populations of beneficial bacteria and stimulate a series of prebiotic effects, such as anti-oxidant, anti-diabetic, anti-tumour. However, the exact structures of MAOs and their prebiotic activities are, to a large extent, unexplored. This review summarizes recent advances in the sources, categories, and structure analysis methods of MAOs,
emphasizing their effects on gut microbiota and its metabolite SCFAs as well as the resulting range of probiotic activities.
Fucoidan is well known to have various biological functions and is often investigated for pharmaceutical applications. Several studies have been conducted on clinical applications of fucoidan in recent years, especially regarding its oral drug delivery. Although fucoidan has shown promising results in various dosage forms, its potential applications as a dietary supplement have been demonstrated, and recent studies show that oral administration of fucoidan is preferred. However, the focus on the oral delivery of fucoidan in recent studies has caused its potency in therapy to be understudied. This review aims to provide results on the promising fucoidan activity by oral administration with in vivo studies. In addition to using it as an active ingredient, the utilization of fucoidan as an excipient in oral drug delivery systems will be discussed. An overview of fucoidan administration by oral delivery in recent promising studies will provide a direction for further investigations in clinical applications, particularly for fucoidan, which has a broad spectrum of bioactive properties.
Purpose
Chronic gastritis is observed in almost half world population. Traditional medications against chronic gastritis might produce adverse effects, so alternative nutritional strategies are needed to prevent the aggravation of gastric mucosal damage. The aim of this study is to evaluate the protective effect of the combination of wheat peptides and fucoidan (WPF) on adults diagnosed with chronic superficial gastritis in a randomized, double-blind, placebo-controlled clinical trial.
Methods
Participants were randomized to receive WPF (N = 53) or placebo (N = 53) once daily for 45 days. Pathological grading of gastric mucosal damage was scored using gastroscopy. Fecal samples were collected for the determination of calprotectin, short chain fatty acids (SCFA) levels and metagenomics analysis. Questionnaires for self-reported gastrointestinal discomforts, life quality and food frequency were collected throughout the study.
Results
WPF intervention reduced gastric mucosal damage in 70% subjects (P < 0.001). Significantly less stomach pain (P < 0.001), belching (P = 0.028), bloating (P < 0.001), acid reflux (P < 0.001), loss of appetite (P = 0.021), increased food intake (P = 0.020), and promoted life quality (P = 0.014) were reported in the WPF group. WPF intervention significantly decreased fecal calprotectin level (P = 0.003) while slightly increased fecal SCFAs level (P = 0.092). In addition, we found altered microbiota composition post-intervention with increased Bifidobacterium pseudocatenulatum (P = 0.032), Eubacterium siraeum (P = 0.036), Bacteroides intestinalis (P = 0.024) and decreased Prevotella copri (P = 0.055).
Conclusions
WPF intervention could be utilized as a nutritional alternative to mitigate the progression of chronic gastritis. Furthermore, WPF played an important role in altering gut microbial profile and SCFA production, which might benefit the lower gastrointestinal tract.
In this review, we focus on the activities transpiring in the anaerobic segment of the sulfur cycle occurring in the gut environment where hydrogen sulfide is produced. While sulfate-reducing bacteria are considered as the principal agents for hydrogen sulfide production, the enzymatic desulfhydration of cysteine by heterotrophic bacteria also contributes to production of hydrogen sulfide. For sulfate-reducing bacteria respiration, molecular hydrogen and lactate are suitable as electron donors while sulfate functions as the terminal electron acceptor. Dietary components provide fiber and macromolecules that are degraded by bacterial enzymes to monomers, and these are fermented by intestinal bacteria with the production to molecular hydrogen which promotes the metabolic dominance by sulfate-reducing bacteria. Sulfate is also required by the sulfate-reducing bacteria, and this can be supplied by sulfate- and sulfonate-containing compounds that are hydrolyzed by intestinal bacterial with the release of sulfate. While hydrogen sulfide in the intestinal biosystem may be beneficial to bacteria by increasing resistance to antibiotics, and protecting them from reactive oxygen species, hydrogen sulfide at elevated concentrations may become toxic to the host.
The aim of this study was to examine the absorption of fucoidan through the intestinal tract. Fucoidan (0.1, 0.5, 1.0, 1.5 and 2.0 mg/mL) was added to Transwell inserts containing Caco-2 cells. The transport of fucoidan across Caco-2 cells increased in a dose-dependent manner up to 1.0 mg/mL. It reached a maximum after 1 h and then rapidly decreased. In another experiment, rats were fed standard chow containing 2% fucoidan for one or two weeks. Immunohistochemical staining revealed that fucoidan accumulated in jejunal epithelial cells, mononuclear cells in the jejunal lamina propria and sinusoidal non-parenchymal cells in the liver. Since we previously speculated that nitrosamine may enhance the intestinal absorption of fucoidan, its absorption was estimated in rats administered N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in their drinking water. Rats were fed 0.2% fucoidan chow (BBN + 0.2% fucoidan rats), 2% fucoidan chow (BBN + 2% fucoidan rats) and standard chow for eight weeks. The uptake of fucoidan through the intestinal tract seemed to be low, but was measurable by our ELISA method. Fucoidan-positive cells were abundant in the small intestinal mucosa of BBN + 2% fucoidan rats. Most fucoidan-positive cells also stained positive for ED1, suggesting that fucoidan was incorporated into intestinal macrophages. The uptake of fucoidan by Kupffer cells was observed in the livers of BBN + 2% fucoidan rats. In conclusion, the absorption of fucoidan through the small intestine was demonstrated both in vivo and in vitro.
The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research.
© 2015. Published by The Company of Biologists Ltd.
present study was aimed to evaluate the antibacterial capability of fucoidan from Sargassum wightii against the chosen human bacterial pathogens. The major chemical constituents of the extracted fucoidan were analyzed by biochemical methods. It showe d that the extracted fucoidan contains 52.86 ± 0.64% of fucose and 29.26 ± 0.83% of sulphate. The antibacterial efficacy was performed by agar well diffusion, minimum inhibitory concentration (MIC) and minimum inhibitory concentration (MBC) method. The maximum antibacterial activity 18.6 ± 0.32 mm was obtained for Vibrio cholera and the minimum activity 8.6 ± 0.26 mm was obtained for Salmonella typhi. Result of this manifested the considerable antibacterial potentiality of fucoidan against human bacterial pathogens. Toxicity of fucoidan was evaluated by brine shrimp toxicity assay. No toxic effect was observed in fucoidan. Our study concluded that fucoidan might be used as natural and safe antibiotics in curing many bacterial diseases. Further study is req uired to get the better understanding of mode of action of fucoidan against the bacterial pathogens.
Seaweeds--or marine macroalgae--notably brown seaweeds in the class Phaeophyceae, contain fucoidan. Fucoidan designates a group of certain fucose-containing sulfated polysaccharides (FCSPs) that have a backbone built of (1→3)-linked α-L-fucopyranosyl or of alternating (1→3)- and (1→4)-linked α-L-fucopyranosyl residues, but also include sulfated galactofucans with backbones built of (1→6)-β-D-galacto- and/or (1→2)-β-D-mannopyranosyl units with fucose or fuco-oligosaccharide branching, and/or glucuronic acid, xylose or glucose substitutions. These FCSPs offer several potentially beneficial bioactive functions for humans. The bioactive properties may vary depending on the source of seaweed, the compositional and structural traits, the content (charge density), distribution, and bonding of the sulfate substitutions, and the purity of the FCSP product. The preservation of the structural integrity of the FCSP molecules essentially depends on the extraction methodology which has a crucial, but partly overlooked, significance for obtaining the relevant structural features required for specific biological activities and for elucidating structure-function relations. The aim of this review is to provide information on the most recent developments in the chemistry of fucoidan/FCSPs emphasizing the significance of different extraction techniques for the structural composition and biological activity with particular focus on sulfate groups.
Fucoidan refers to a type of polysaccharide which contains substantial percentages of L-fucose and sulfate ester groups, mainly derived from brown seaweed. For the past decade fucoidan has been extensively studied due to its numerous interesting biological activities. Recently the search for new drugs has raised interest in fucoidans. In the past few years, several fucoidans' structures have been solved, and many aspects of their biological activity have been elucidated. This review summarizes the research progress on the structure and bioactivity of fucoidan and the relationships between structure and bioactivity.
The anti-inflammatory, antiangiogenic, anticoagulant, and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition on their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitro evaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L. digitata, Fucus evanescens, F. serratus, F. distichus, F. spiralis, and Ascophyllum nodosum could serve as P-selectin inhibitors. All fucoidans, except that from Cladosiphon okamuranus carrying substantial levels of 2-O-alpha-D-glucuronopyranosyl branches in the linear (1-->3)-linked poly-alpha-fucopyranoside chain, exhibited anticoagulant activity as measured by activated partial thromboplastin time whereas only fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. evanescens displayed strong antithrombin activity in a platelet aggregation test. The last fucoidans potently inhibited human umbilical vein endothelial cell (HUVEC) tubulogenesis in vitro and this property correlated with decreased levels of plasminogen-activator inhibitor-1 in HUVEC supernatants, suggesting a possible mechanism of fucoidan-induced inhibition of tubulogenesis. Finally, fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. vesiculosus strongly blocked MDA-MB-231 breast carcinoma cell adhesion to platelets, an effect which might have critical implications in tumor metastasis. The data presented herein provide a new rationale for the development of potential drugs for thrombosis, inflammation, and tumor progression.
Fucoidan is a functional food that possesses various biological activities. This study aims to determine the effects of fucoidan from Undaria pinnatifida on gut microbiota and dyslipidemia in BALB/c mice. In vitro, fucoidan could support the growth of three lactic acid bacteria strains. The test groups with high fat diet (HFD) were gavaged with fucoidan at a dose of 50 mg/kg/day or 100 mg/kg/day for 8 weeks. Fucoidan decreased total serum cholesterol (P < 0.05), LDL-C (P < 0.05) and liver cholesterol levels (P < 0.05). The steatosis of liver was improved in fucoidan-supplemented groups. Fucoidan also decreased the expression of cholesterol related proteins (HMGCR, SREBP-2) in liver (P < 0.05). The 16S rRNA gene sequence analysis of gut microbiota showed that fucoidan increased abundance of Bacteroidetes and Alloprevotella, whereas decreased abundance of Firmicutes, Staphylococcus and Streptococcus. Taken together, the results suggest fucoidan alleviates dyslipidemia and modulates gut microbiota in HFD-fed mice.
Recently, there has been an unprecedented interest in the study of gut microbiota during treatment of diseases byfunctional foods. However, although great progresses have been made, a significant knowledge gap still exists.The knowledge gap, as argued here, is that in most of the studies we failed to establish a cause–effect relationshipbetween attenuation of the diseases and changes of the gut microbiota. The lack of causation studies deteriorates the foundation for the use of functional foods in disease management that aim to target the gut microbiota. In this sense, we propose here that future studies on the interactions of functional foods and gut microbiota during the treatment of diseases must move beyond correlation to causation, and only after a cause–effect relationship has been established can we fully realize the therapeutic potential of functional foods in the upcoming era of microbiota targeted precision nutrition.
Diabetes is a complicated endocrine and metabolic disorder, which has become an epidemic health issue worldwide. Fucoidan is extensively distributed in the brown algae and several marine invertebrates exhibiting diverse biological activities. In the present study, the physicochemical property of Sargassum fusiforme fucoidan (SFF) and its effects on streptozotocin (STZ)-induced diabetic mice and gut microbiota were investigated. Diabetes mice not only showed abnormal blood glucose, but also accompanied by multiple symptoms, such as gradual emaciation, decreased body weight, increased food and water intake. Compared with diabetic mice after 6-week treatment, administration of SFF significantly decreased the fasting blood glucose, diet and water intake. Furthermore, SFF attenuated the pathological change in the heart and liver, improved the liver function, and suppressed oxidative stress in STZ-induced diabetic mice. Simultaneously, SFF significantly altered the gut microbiota in the faeces of diabetic mice, decreased the relative abundances of the diabetes-related intestinal bacteria, which is a potential mechanism for relieving the symptoms of diabetes. Therefore, SFF might be considered as one of the promising complementary and alternative medicines for the management of diabetes mellitus in future.
Fucoidans from sea cucumbers are potential functional food ingredients with a well-defined repeating structure. However, there have been fewer function studies of fucoidan oligosaccharides. In the present study, we first compare the functional effects of fucoidan oligosaccharides from Pearsonothuria graeffei (Dfuc-Pg) and Isostichopus Badionotus (Dfuc-Ib) in a high fat diet (HFD)-fed mouse model. Sulfation pattern was the only structural difference in the two fucoidan oligosaccharides. Both Dfuc-Pg and Dfuc-Ib inhibited hyperlipidemia, obesity, and inflammation caused by HFD. Notably, Dfuc-Pg could inhibit macrophages infiltrating into adipose tissue and had better anti-inflammatory activity than Dfuc-Ib. Meanwhile, both fucoidan oligosaccharides could reverse gut microbiota dysbiosis, particularly colonic microbiota dysbiosis by decreasing abundance of Firmicutes while increasing abundance of Bacteroidetes. However, Dfuc-Ib dominated with 2-O-sulfo groups increased abundance of Proteobacteria. Dfuc-Pg dominated with 4-O-sulfo groups maintained a better balanced gut microbiota profile. Our results shed a new insight into structure-function relationship of sulfated oligosaccharides.
Objectives:
Dyslipidemia is an important risk factor for cardiovascular diseases. Fucoidan (FUC) is a polysaccharide extracted from brown marine algae with various biological activities. Galactooligosaccharides (GOS) are important prebiotics that exert benefits on the intestinal microbiota. The aim of this study was to investigate the effects of FUC and GOS on dyslipidemia in rats by modulating the gut microbiota and bile acid metabolism.
Methods:
Twenty-four male inbred Sprague-Dawley (SD) rats aged 8 wk were fed a normal or high-fat diet (HFD) for 8 wk. During the feeding period, rats were gavaged with normal saline solution, FUC solution (100 mg/kg),or GOS solution (800 mg/kg), or a combination of both once daily. Serum biochemical parameters were determined, and the gut microbiota were analyzed via 16S rRNA gene sequencing. Bile salt hydrolase (BSH) activity in the small intestinal contents was also analyzed. The effects of FUC and GOS on Lactobacillus casei DM8121 were analyzed in vitro.
Results:
In rats, GOS and FUC supplementation significantly improved serum total cholesterol, low-density lipoprotein cholesterol, lipopolysaccharide, serum total bile acid, hepatic tissue steatosis, aortic arch injury, gut microbiota, serum high-density lipoprotein cholesterol, cholesterol 7-alpha hydroxylase expression in the liver, and BSH activity in the small intestinal contents. In an in vitro experiment, GOS and FUC supplementation significantly increased L. casei DM8121's BSH activity.
Conclusions:
In rats, FUC and GOS supplementation improved serum dyslipidemia, gut microbiota, BSH activity, and bile acid metabolism-related pathways. In vitro, GOS and FUC supplementation increased L. casei DM8121's BSH activity.
To investigate the degradation and utilization of fucoidan from Laminaria japonica of different molecular weights with human gut microbiota, we sampled human gut microbiota from five volunteers in vitro. High- and low-molecular-weight fucoidan (coded HMWF and LMWF, respectively) were fermented with the microbiota in anaerobic culture system in vitro for 48h. TLC and PAGE were used to analyze the degradation of fucoidan. PMP-HPLC and GC were used to analyze the monosaccharide composition and short chain fatty acids in fermentation product, respectively. Results show that the content of oligosaccharides and low-molecular-weight fucoidan (10-20kDa) decreased markedly, while the monosaccharide composition of degradation products remained unchanged, indicating that the LMWF could be degraded entirely and utilized by human gut microbiota in anaerobic culture system in vitro. However, only small amounts of HMWF (>20kDa) could be degraded to oligosaccharides, and the proportions of galactose and mannose in the fermentation product decreased significantly. GC analysis showed that both LMWF and HMWF could be degraded to acetic acid, propionic acid and butyric acid (short-chain fatty acids). Branched-chain fatty acids (isobutyric acid and isovaleric acid) and valeric acid could be detected in HMWF medium only. Therefore, human gut microbiota can degrade and utilize complex fucoidan oligosaccharides and low-molecular-weight fractions from L. japonica in anaerobic culture system in vitro; however, it could be difficult to degrade a large-molecular-weight fucoidan with human gut microbiota. All sugars in the fucoidan oligosaccharides and large-molecular-weight fucoidan could be utilized by the microbiota to produce short-chain fatty acids, which is good for intestinal tract health. However, only LWMF could inhibit the produce of branched-chain fatty acids with human gut microbiota.
A high-fat diet (HFD) has been a major contributor to increasing morbidity caused by metabolic syndromes. Functional foods from natural sources are potential choices for addressing metabolic diseases because they provide many health benefits with a low level of adverse side effects. In our former reports, fucoidan from Pearsonothuria graeffei (fuc-Pg), a type of sulfated polysaccharides with a repeating structure, was shown to be a potential functional food ingredient. In this work, we investigated the effects of fuc-Pg on gut microbiota dysbiosis and metabolic syndromes caused by HFD. Our results indicated that fuc-Pg could reduce weight gains, alleviate hyperlipidemia, and protect the liver from steatosis in HFD-fed mice. Meanwhile, fuc-Pg decreases serum inflammatory factors and reduces macrophages infiltrating into adipose tissue. The gut microbiota dysbiosis caused by HFD was alleviated by administration of fuc-Pg, mainly working in the colon. Fuc-Pg increased abundances of Bacteroidetes and Actinobacteria while decreased Firmicutes and Proteobacteria. Our results indicated that fuc-Pg could be a functional food for gut microbiota dysbiosis and metabolic syndromes.
Recent research have showed that the intestinal flora are related to the occurrence and progress of breast cancer. This study was to investigate the effect of fucoidan on intestinal flora and intestinal barrier function in rats with 7, 12-Dimethyl Benz[a]anthracene(DMBA)-induced breast cancers. Sixty female Sprague-Dawley rats were randomly assigned to control group, model group, and the F1 and F2 groups, which were fed fucoidan at concentrations of 200 and 400 mg/kg•bw (body weight), respectively. Intestinal histopathological analysis was performed and 16S rDNA high-throughput sequencing was used to provide an overview of the intestinal flora composition. The contents of D-lactic acid (D-LA), diamine oxidase (DAO) and endotoxin in plasma were detected by ELISA. Expression levels of the tight junction (TJ) proteins, phosphorylated p38 MAPK and ERK1/2 were measured using western blotting. Our results suggested the intestinal wall of model group were damaged. However, after fucoidan intervention, the villi were gradually restored. ELISA showed the levels of plasma endotoxin, D-LA and DAO decreased in F1 and F2 groups compared to those in model group. Fucoidan treatment also increased the expressions of ZO-1, Occludin, Claudin-1 and Claudin-8. Furthermore, the expression levels of phosphorylated p38 MAPK and ERK1/2 were upregulated in fucoidan treatment groups. The results of 16S rDNA high-throughput sequencing indicated that fucoidan increased diversity of intestinal microbiota and induced changes in microbial composition.with increased Bacteroidetes/Firmicutes phylum ratio. In conclusion, the supplement of fucoidan could improve the fecal microbiota composition and repair the intestinal barrier function. The study suggested the use of fucoidan as an intestinal flora modulator for potential prevention of breast cancer.
The gut microbiota that resides in the mammalian intestine plays a critical role in host health, nutrition, metabolic and immune homeostasis. As symbiotic bacteria, these microorganisms depend mostly on non-digestible fibers and polysaccharides as energy sources. Dietary polysaccharides that reach the distal gut are fermented by gut microbiota and thus exert a fundamental impact on intestinal ecology. Marine polysaccharides contain a class of dietary fibers that are widely used in food and pharmaceutical industries (e.g., agar and carrageenan). In this regard, insights into fermentation of marine polysaccharides and its effects on intestinal ecology are of vital importance for understanding the beneficial effects of these glycans. Here, in this review, to provide an overlook of current advances and facilitate future studies in this field, we describe and summarize up-to-date findings on how marine polysaccharides are metabolized by gut microbiota and what effects these polysaccharides have on intestinal ecology.
Cyclophosphamide (cy) is a widely used cancer drug. Many researchers have focused on prevention and alleviation of its side effects, particularly damage to the intestinal mucosal barrier. In this study, we examined the effects of fucoidan, isolated from Acaudina molpadioides, on mice with intestinal mucosa damage induced by cyclophosphamide. Our results showed that fucoidan intervention could relieve injury such as decreasing inflammation and increasing the expression of tight junction proteins, and 50-kDa fucoidan significantly increase the abundance of short chain fatty acids (SCFAs) producer-Coprococcus, Rikenella, and Butyricicoccus (p <0.05, p <0.001, and p <0.05, respectively) species within the intestinal mucosa compared with cyclophosphamide group, as determined by 16S rDNA gene high-throughput sequencing. In addition, SCFAs, particularly propionate, butyrate, and total SCFAs, were increased in feces, and SCFA receptors were upregulated in small intestine. The protective effects of fucoidan on cyclophosphamide treatment may be associated with gut microflora, and 50-kDa fucoidan had superior effects. Therefore, fucoidan may have applications as an effective supplement to protect against intestinal mucosal barrier damage during chemotherapy.
Recently, fucoidan has been proposed as a potential prebiotic agent for functional food and pharmaceutical development. However, while previous studies illustrated favorable modulations of gut microbiota by fucoidan, changes in the overall microbial structure remain elusive. In the present study, modulations of gut microbiota by different fucoidans were studied using high throughput sequencing and bioinformatics analysis. We found that at the expense of opportunistic pathogenic bacteria such as Peptococcus, the abundance of beneficial bacteria including Lactobacillus and Ruminococcaceae was significantly increased in response to fucoidan treatment. Besides, by maintaining a more balanced composition of gut microbiota, dietary fucoidan also significantly reduced the antigen load and the inflammatory response in the host as evidenced by the decreased serum lipopolysaccharide-binding protein levels. Collectively, our results indicate that fucoidan can be used as a gut microbiota modulator for health promotion and treatment of intestinal dysbiosis.
Colonic health: Fermentation and short chain fatty acids
- J M Wong
- R De Souza
- C W Kendall
- A Emam
- D J Jenkins
Wong, J. M., De Souza, R., Kendall, C. W., Emam, A., & Jenkins, D. J. (2006). Colonic
health: Fermentation and short chain fatty acids. Journal of Clinical Gastroenterology,
40, 235-243.