Lipid metabolism regulation by dietary polysaccharides with different structural properties.

Lipid metabolism plays an important role in energy homeostasis maintenance in response to stress. Nowadays, hyperlipidemia-related chronic diseases such as obesity, diabetes, atherosclerosis, and fatty liver pose significant health challenges. Dietary polysaccharides (DPs) have gained attention for their effective lipid-lowering properties. This review examines the multifaceted mechanisms that DPs employ to lower lipid levels in subjects with hyperlipidemia. DPs could directly inhibit lipid intake and absorption, promote lipid excretion, and regulate key enzymes involved in lipid metabolism pathways, including triglyceride and cholesterol anabolism and catabolism, fatty acid oxidation, and bile acid synthesis. Additionally, DPs indirectly improve lipid homeostasis by modulating gut microbiota composition and alleviating oxidative stress. Moreover, the lipid-lowering mechanisms of particular structural DPs (including ß-glucan, pectin, glucomannan, inulin, arabinoxylan, and fucoidan) are summarized. The relationship between the structure and lipid-lowering activity of DPs is also discussed based on current researches. Finally, potential breakthroughs and future directions in the development of DPs in lipid-lowering activity are discussed. The paper could provide a reference for further exploring the mechanism of DPs for lipid regulations and utilizing DPs as lipid-lowering dietary ingredients.

Insoluble/soluble fraction ratio determines effects of dietary fiber on gut microbiota and serum metabolites in healthy mice.

Both soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) play pivotal roles in maintaining gut microbiota homeostasis; whether the effects of the different ratios of IDF and SDF are consistent remains unclear. Consequently, we selected SDFs and IDFs from six representative foods (apple, celery, kale, black fungus, oats, and soybeans) and formulated nine dietary fiber recipes composed of IDF and SDF with a ratio from 1 : 9 to 9 : 1 (NDFR) to compare their impact on microbial effects with healthy mice. We discovered that NDFR treatment decreased the abundance of Proteobacteria and the ratio of Firmicutes/Bacteroidetes at the phylum level. The α diversity and relative richness of Parabacteroides and Prevotella at the genus level showed an upward trend along with the ratio of IDF increasing, while the relative abundance of Akkermansia at the genus level and the production of acetic acid and propionic acid exhibited an increased trend along with the ratio of SDF increasing. The relative abundance of Parabacteroides and Prevotella in the I9S1DF group (the ratio of IDF and SDF was 9 : 1) was 1.72 times and 5.92 times higher than that in the I1S9DF group (the ratio of IDF and SDF was 1 : 9), respectively. The relative abundance of Akkermansia in the I1S9DF group was 17.18 times higher than that in the I9S1DF group. Moreover, a high ratio of SDF (SDF reaches 60% or more) enriched the glycerophospholipid metabolism pathway; however, a high ratio of IDF (IDF reaches 80% or more) regulated the tricarboxylic acid cycle. These findings are helpful in the development of dietary fiber supplements based on gut microbiota and metabolites.

A review: Effects of microbial fermentation on the structure and bioactivity of polysaccharides in plant-based foods.

Fermented plant-based foods that catering to consumers' diverse dietary preferences play an important role in promoting human health. Recent exploration of their nutritional value has sparked increasing interest in the structural and bioactive changes of polysaccharides during fermentation, the essential components of plant-based foods which have been extensively studied for their structures and functional properties. Based on the latest key findings, this review summarized the dominant fermented plant-based foods in the market, the involved microbes and plant polysaccharides, and the corresponding modification in polysaccharides structure. Further microbial utilization of these polysaccharides, influencing factors, and the potential contributions of altered structure to the functions of polysaccharides were collectively illustrated. Moreover, future research trend was proposed, focusing on the directional modification of polysaccharides and exploration of the mechanisms underlying structural changes and enhanced biological activity during fermentation.

Parabacteroides distasonis ameliorates insulin resistance via activation of intestinal GPR109a.

Gut microbiota plays a key role in insulin resistance (IR). Here we perform a case-control study of Chinese adults (ChiCTR2200065715) and identify that Parabacteroides distasonis is inversely correlated with IR. Treatment with P. distasonis improves IR, strengthens intestinal integrity, and reduces systemic inflammation in mice. We further demonstrate that P. distasonis-derived nicotinic acid (NA) is a vital bioactive molecule that fortifies intestinal barrier function via activating intestinal G-protein-coupled receptor 109a (GPR109a), leading to ameliorating IR. We also conduct a bioactive dietary fiber screening to induce P. distasonis growth. Dendrobium officinale polysaccharide (DOP) shows favorable growth-promoting effects on P. distasonis and protects against IR in mice simultaneously. Finally, the reduced P. distasonis and NA levels were also validated in another human type 2 diabetes mellitus cohort. These findings reveal the unique mechanisms of P. distasonis on IR and provide viable strategies for the treatment and prevention of IR by bioactive dietary fiber.

Comprehensive evaluation of the prebiotic properties of Dendrobium officinale polysaccharides, ß-glucan, and inulin during in vitro fermentation via multi-omics analysis.

Dietary fiber is crucial for human health mainly due to its impact on gut microbiota structure and metabolites. This study aimed to investigate the impact of Dendrobium officinale polysaccharides (DOP) and two common fibers (ß-glucan and inulin) on the gut microbiome structure and metabolic profile in vitro. Fecal samples were obtained from 30 healthy volunteers, which were then individually subjected to fermentation with each type of fiber. The results revealed that all fibers were efficiently degraded by gut microbiota, with DOP exhibiting a slower fermentation rate compared to ß-glucan and inulin. The fermentation of all fibers led to a significant increase in the production of short-chain fatty acids (SCFAs) and a reduction in branched-chain fatty acids (BCFAs), sulfides, phenols, and indole. Moreover, the abundance of unclassified Enterobacteriaceae, which was positively correlated with sulfide, phenols, and indole levels, was significantly reduced by all fibers. Additionally, DOP specifically promoted the growth of Parabacteroides, while ß-glucan and inulin promoted the growth of Bifidobacterium and Faecalibacterium. Taken together, these findings enhance our understanding of the role of DOP, ß-glucan, and inulin in modulating gut microbiota and metabolites, where the fermentation with fecal bacteria from different volunteers could provide valuable insights for personalized therapeutic approaches.

Agrocybe cylindracea fucoglucogalactan induced lysosome-mediated apoptosis of colorectal cancer cell through H3K27ac-regulated cathepsin D.

Inducing lysosomal dysfunction is emerging as a promising means for cancer therapy. Agrocybe cylindracea fucoglucogalactan (ACP) is a bioactive ingredient with anti-tumor activity, while its mechanism remains obscure. Herein, we found that ACP visibly inhibited the proliferation of colorectal cancer cells, and the IC50 value on HCT-116 cells (HT29 cells) was 490 µg/mL (786.4 µg/mL) at 24 h. RNA-seq showed that ACP regulated mitochondria, lysosome and apoptosis-related pathways. Further experiments proved that ACP indeed promoted apoptosis and lysosomal dysfunction of HCT-116 cells. Moreover, ChIP-seq revealed that ACP increased histone-H3-lysine-27 acetylation (H3K27ac) on CTSD (cathepsin D) promoter in HCT-116 cells, thus facilitating the binding of transcription factor EB (TFEB), and resulted in ascension of CTSD expression. Additionally, ACP triggered mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential and increasing pro-apoptotic protein levels. Notably, Pepstatin A (CTSD inhibitor) availably alleviated ACP-induced apoptosis. Taken together, our results indicated that ACP induced lysosome-mitochondria mediated apoptosis via H3K27ac-regulated CTSD in HCT-116 cells. This study indicates that ACP has anti-cancer potential in the treatment of colorectal cancer.

Improved Loading Capacity and Viability of Probiotics Encapsulated in Alginate Hydrogel Beads by In Situ Cultivation Method.

The objective of this research was to encapsulate probiotics by alginate hydrogel beads based on an in situ cultivation method and investigate the influences on the cell loading capacity, surface and internal structure of hydrogel beads and in vitro gastrointestinal digestion property of cells. Hydrogel beads were prepared by extrusion and cultured in MRS broth to allow probiotics to grow inside. Up to 10.34 ± 0.02 Log CFU/g of viable cell concentration was obtained after 24 h of in situ cultivation, which broke through the bottleneck of low viable cell counts in the traditional extrusion method. Morphology and rheological analyses showed that the structure of the eventually formed probiotic hydrogel beads can be loosed by the existence of hydrogen bond interaction with water molecules and the internal growth of probiotic microcolonies, while it can be tightened by the acids metabolized by the probiotic bacteria during cultivation. In vitro gastrointestinal digestion analysis showed that great improvement with only 1.09 Log CFU/g of loss in viable cells was found after the entire 6 h of digestion. In conclusion, the current study demonstrated that probiotic microcapsules fabricated by in situ cultivation method have the advantages of both high loading capacity of encapsulated viable cells and good protection during gastrointestinal digestion.

Effects of xanthan gum, konjac glucomannan, and arabinogalactan on the in vitro digestion and fermentation characteristics of biscuits.

Background: Diabetes and its complications have a significant economic impact on individuals and their families. A diet with a low glycemic index (GI) and high fiber content is considered to be associated with the control of blood glucose. Scope and approach: This study explored the effect of polysaccharides, i.e., xanthan gum (BXG), konjac glucomannan (BKG), and arabinogalactan (BAG), on the digestive and prebiotic characteristics of biscuits using a simulated digestion and fermentation model in vitro. Also, the rheological property and structural properties of the polysaccharides were measured to clarify their structure-activity relationships. Key findings and conclusions: During simulated gastrointestinal digestion, the results showed that three types of biscuits containing polysaccharides were low GI foods (estimated GI < 55), in which BAG had the lowest estimated GI value. During in vitro fermentation with diabetic or healthy subjects' fecal microbiota, the three types of biscuits containing polysaccharides (after digestion) decreased the fermentation pH, increased the level of short-chain fatty acids, and modulated the microbiota composition over time. Among the three types of biscuits, BAG increased the abundance of Bifidobacterium and Lactobacillus during fermentation in diabetic and healthy subjects' fecal microbiota. These results showed that the addition of a lower-viscosity polysaccharide (arabinogalactan) may be more beneficial for the blood glucose control of biscuits.

Effects of Lactobacillus casei NCU011054 on immune response and gut microbiota of cyclophosphamide induced immunosuppression mice.

Lactobacillus (L.) casei NCU011054 isolated from infant feces has been proven to be a potential probiotic in vitro. The present study aimed to investigate the effects of L. casei NCU011054 on the immune response and gut microbiota in cyclophosphamide (CP)-induced immunosuppression mice. Results indicated that L. casei NCU011054 could increase the levels of mucin (Muc2) and tight junction proteins (ZO-1, occludin and claudin-1). Moreover, L. casei NCU011054 was found to upregulate TLRs/NF-κB pathway (TLR-2, TLR-4, TLR-6, p65 and NF-κB) and two transcription factors (T-bet and GATA-3) mRNA levels, and enhance the number of CD4+T cells. Th1-related cytokines (IL-12p70, IFN-γ and TNF-α) and Th2-related cytokines (IL-2, IL-4, IL-6 and IL-10) significantly increased after L. casei NCU011054 treatment. More importantly, L. casei NCU011054 increased the ratio of T-bet to GATA-3 and IFN-γ to IL-4. Apart from these, L. casei NCU011054 remodeled gut microbiota and modulated gut metabolites in CP-induced immunosuppressed mice. The correlation analysis showed that Lactobacillus upregulated by L. casei NCU011054 was positively correlated with TLRs/NF-κB pathway, and the ratio of T-bet to GATA-3 and IFN-γ to IL-4. All findings revealed that L. casei NCU011054 could improve intestinal immune dysfunction and modulate Th1/Th2 balance via TLRs/NF-κB pathway in CP-induced immunosuppressed mice.

The incorporation of peach gum polysaccharide into soy protein based microparticles improves probiotic bacterial survival during simulated gastrointestinal digestion and storage.

The objective of this research was to investigate the in vitro gastrointestinal digestion and storage properties of Lactobacillus plantarum 550 encapsulated in soy protein isolate (SPI) and peach gum polysaccharide (PG) through spray drying. High survival rates (>8.1 Log CFU/g) were obtained for all encapsulation formulas containing PG. Combination of SPI and PG showed positive effects on both gastric resistance and storage stability of cells. Among the formulas tested, sample of SPI:PG = 3:1 showed the highest survival (7.88 ± 0.12 Log CFU/g), corresponding to the strongest electrostatic interaction between SPI and PG. With PG content increasing, the storage stability of probiotic was also enhanced, as PG could reduce the moisture content within microcapsules as well as scavenge free radicals generated during storage. In conclusion, the current study demonstrates that SPI combined with PG may provide effective protection to cells not only during spray drying, but also during storage and gastrointestinal digestion.

Effects of boiling and steaming process on dietary fiber components and in vitro fermentation characteristics of 9 kinds of whole grains.

Whole grains (WGs) are considered as the representative sources of dietary fiber (DF). Thermal treatments can change the properties of DF, and potentially affecting the gut microbiota as well as human health. In this study, DF content and in vitro fermentation characteristics of 9 kinds of WGs (highland barley, barley, buckwheat, proso millet, quinoa, sorghum, coix seed, foxtail millet, and oats) after boiling and steaming treatments were compared. It was found that boiling and steaming treatments could both increase DF content in these grains, except for barley and foxtail millet. Processed WGs could regulate beneficial microbial genus, such as Bifidobacterium, Prevotella, Megamona and Megasphaera. Oats, quinoa, highland barley, and buckwheat after boiling treatment can produce more total short-chain fatty acids (SCFAs) than steaming treatment (p < 0.05), while barley, foxtail millet and coix seed showed opposite results. This study can provide data support for the design of WGs diets and the development of WGs products which are beneficial for gut health.

Tea polyphenol and epigallocatechin gallate ameliorate hyperlipidemia via regulating liver metabolism and remodeling gut microbiota.

Hyperlipidemia can directly cause metabolic diseases that seriously endanger disorder and metabolism and gut health. Tea polyphenol (TP) and epigallocatechin gallate (EGCG) was found to improve blood lipid levels and gut microbiota. This study aimed to investigate the effects of TP and EGCG on alleviating hyperlipidemia and liver fat accumulation with physiology, genomics, and metabolomics. Results showed that both TP and EGCG reduced body weight, and TP showed advantages in the decrease of serum cholesterol and triglycerides in hyperlipidemic rats induced by the high-fat diet. Moreover, EGCG may protect liver function via reducing the glycerophospholipids increased by high-fat diet intervention. TP remodeled the gut microbiota composition and enriched the abundance of beneficial bacteria (Bacteroides, Faecalibacterium, Parabacteroides, Akkermansia), and EGCG may improve gut health via promoting the acid-producing bacteria (such as Butyricimonas, Desulfovibrio). The above results provided new insights into the hypolipidemic mechanism of TP and EGCG.

Interaction between four galactans with different structural characteristics and gut microbiota.

Human gut microbiota played a key role in maintaining and regulating host health. Gut microbiota composition could be altered by daily diet and related nutrients. Diet polysaccharide, an important dietary nutrient, was one kind of biological macromolecules linked by the glycosidic bonds. Galactans were widely used in foods due to their gelling, thickening and stabilizing properties. Recently, effects of different galactans on gut microbiota have attracted much attention. This review described the structural characteristics of 4 kinds of galactans, including porphyran, agarose, carrageenan, and arabinogalactan, along with the effects of different galactans on gut microbiota and production of short-chain fatty acids. The ability of gut microbiota to utilize galactans with different structural characteristics and related degradation mechanism were also summarized. All these four galactans could be used by gut Bacteroides. Besides, the porphyran could be utilized by Lactobacillus and Bifidobacterium, while the arabinogalactan could be utilized by Lactobacillus, Bifidobacterium and Roseburia. Four galactans with significant difference in molecular weight/degree of polymerization, glycosidic linkage, esterification, branching and monosaccharide composition required gut microbes which could utilize them have corresponding genes encoding the corresponding enzymes for decomposition. This review could help to understand the relationship between galactans with different structural characteristics and gut microbiota, and provide information for potential use of galactans as functional foods.

Polysaccharides from fermented coix seed modulates circulating nitrogen and immune function by altering gut microbiota.

Coix lachryma-jobi L. seed is an important food item in Asia with culinary and medicinal values. The effects of non-fermented coix seed (NFC), fermented coix seed with Lactobacillus plantarum NCU137 (FC) and polysaccharides from NFC, FC (FCP) on mice circulating nitrogen and immune disorder induced by high relative humidity (RH, 90 ± 2%) exposure were compared. All the treatments reduced circulating nitrogen (BUN and ammonia) might via increasing excretion of fecal nitrogen induced by altering gut microbiota. In comparison, FC and FCP restored erythrocyte morphology by promoting erythrocyte Na+/K+ ATPase activity more effectively, and immune function was modulated by reducing plasma IgM and IFN-γ levels, up-regulating IL-4 and IL-6 levels. Herein, these results indicated that FCP, as the main active ingredient in FC, modulated circulating nitrogen through altering gut microbiota, and restored immune homeostasis by regulating Th1/Th2 cytokines in mice receiving high RH exposure.

Structural characteristic of pectin-glucuronoxylan complex from Dolichos lablab L. hull.

Polysaccharides are important constituents in Dolichos lablab hull. Herein, pectin-glucuronoxylan complex from D. lablab hull designated as DLHP-3 (D. lablab hull polysaccharide,) was prepared by ion exchange and gel permeation chromatography, and further characterized by acid degradation and enzymatic hydrolysis, methylation combined with GC-MS, NMR and MALDI-TOF-MS analysis. Both of pectin and glucuronoxylan regions were found in DLHP-3. The glucuronoxylan region consisted of a →4)-ß-Xylp-(1→ backbone with branches of α-GlcpA-(1→ substituted at O-2 site, and the ratio of xylose to glucuronic acid was about 5:1. Acetyl groups were mainly attached to O-3 site of →2,4)-ß-Xylp-(1→ residues. The main chain of pectin region could be represented by →4)-α-GalpA-(1→4)-α-GalpA-(1→ and →2)-α-Rhap-(1→4)-α-GalpA-(1→ with partial methyl-esterification. The side chains were deduced to embrace arabinan and arabinogalactan linked to rhamnogalacturonan-I region. Pectin was probably covalently bound to glucuronoxylan. Our findings uncovered the molecular structure of pectin-glucuronoxylan complex from D. lablab hull.

Gut firmicutes: Relationship with dietary fiber and role in host homeostasis.

Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human gut. Accumulating evidence suggests that dietary fiber plays a crucial role in host health, yet most studies have focused on how the dietary fiber affects health through gut Bacteroides. More recently, gut Firmicutes have been found to possess many genes responsible for fermenting dietary fiber, and could also interact with the intestinal mucosa and thereby contribute to homeostasis. Consequently, the relationship between dietary fiber and Firmicutes is of interest, as well as the role of Firmicutes in host health. In this review, we summarize the current knowledge regarding the molecular mechanism of dietary fiber degradation by gut Firmicutes and explain the communication pathway of the dietary fiber-Firmicutes-host axis, and the beneficial effects of dietary fiber-induced Firmicutes and their metabolites on health. A better understanding of the dialogue sustained by the dietary fiber-Firmicutes axis and the host could provide new insights into probiotic therapy and novel dietary interventions aimed at increasing the abundance of Firmicutes (such as Faecalibacterium, Lactobacillus, and Roseburia) to promote health.

Dietary fiber-induced gut Firmicutes and their metabolites exhibit relevant health-promoting functions.Most of dietary fiber have a great effect on gut Firmicutes.Mechanisms of dietary fiber uptake by gut Firmicutes are outlined.Mechanisms of dietary fiber- gut Firmicutes-host interactions require more investigation for the development of dietary fiber in food production and host health.

Resistant starches and gut microbiota.

Resistant starches (RS), which are considered as one of the dietary fibers, could exert widely beneficial impacts, reduce fat accumulation, show significant effects on regulating blood glucose metabolism and insulin levels, and have protective effects on the gut. Five types of RS have different responses to chronic disease by modulating gut microbiota. Short-chain fatty acids are the linkage between gut microbiota and RS, and RS could improve the metabolism of gut microbiota as well as increase the abundance of beneficial microbes in the gut. The composition of gut microbiota is associated with RS properties, which is reflected by the changes of butyrate-producing bacteria primarily influenced by consumption of RS with various fine structures and types of crystallinities. RS with different fine structures and properties is consumed to varying degrees by gut microbiota, which can be applied to produce functional foods for gut health in future.

Gut microbial utilization of xylan and its implication in gut homeostasis and metabolic response.

Xylan as the second most abundant indigestible carbohydrate found in nature attracts great interests of researchers, nutritionist and consumers due to its various health benefits. However, accumulated studies indicate the interactions with gut microbiota greatly affect these benefits, and significant progress has been made over the past few years to understand how microbes utilize xylan at gene level. In this review, we focused on gut xylanolytic microbes and xylan's physico-chemical features, summarized the xylanases needed for complete xylan decomposition, their substrate specificity and the presence in gut microbes, as well as microbial degradation of xylan in single strain mode and cooperation mode. Xylan utilization system were discussed with different phyla. Furthermore, the implications on intestinal homeostasis and metabolic response were reviewed with clinical effects emphasized, and highlight is placed on specific gut microbes and the complexity of xylan structure to provide a clue for the inconsistent results in human studies. CHEMICAL COMPOUNDS: xylan; arabinoxylan, glucuronoxylans; glucuronoarabinoxylans; xylo-oligosaccharides; arabinoxylo-oligosaccharides.

Short-term exposure to high relative humidity increases blood urea and influences colonic urea-nitrogen metabolism by altering the gut microbiota.

Introduction: Colonic urea-nitrogen metabolites have been implicated in the pathogenesis of certain diseases which can be affected by environmental factors. Objectives: We aimed to explore the influence of ambient humidity on colonic urea-nitrogen metabolism. Methods: Blood biochemical indexes, metabolites of intestinal tract, and gut microbiota composition of mice (n = 10/group) exposed to high relative humidity (RH, 90 ± 2%) were analyzed during the 14-day exposure. Results: After 12-h exposure, plasma blood urea nitrogen (BUN) level increased along with a decrease in the activity of erythrocyte Na+/K+ -ATPase. Moreover, abnormal erythrocyte morphologies appeared after 3 days of exposure. The colonic BUN and ammonia levels increased significantly after the 12-h and 24-h exposure, respectively. The colonic level of amino acids, partly synthesized by gut microbiota using ammonia as the nitrogen source, was significantly higher on the 7th day. Furthermore, the level of fecal short-chain fatty acids was significantly higher after 3-day exposure and the level of branched-chain fatty acids increased on the 14th day. Overall, gut microbiota composition was continuously altered during exposure, facilitating the preferential proliferation of urea-nitrogen metabolism bacteria. Conclusion: Our findings suggest that short-term high RH exposure influences colonic urea-nitrogen metabolism by increasing the influx of colonic urea and altering gut microbiota, which might further impact the host health outcomes.

Arabinoxylan ameliorates type 2 diabetes by regulating the gut microbiota and metabolites.

Type 2 diabetes (T2D) is a metabolic disease characterized by hyperglycemia. Intake of dietary fiber is inversely associated with risks of T2D. Here, metabolomics and 16S rRNA gene sequencing were employed to investigate the effects of arabinoxylan on gut microbiota and their metabolites in type 2 diabetic rats. T2D increased the abundance of opportunistic pathogens (such as Desulfovibrio and Klebsiella) and the levels of 12α-hydroxylated bile acids and acylcarnitines (C3) in diabetic rats, which eventually contribute to insulin resistance and hyperglycemia. Supplementation with arabinoxylan promoted the growth of fiber-degrading bacteria to increase short-chain fatty acids (SCFAs), as well as decreased the abundance of opportunistic pathogens. Arabinoxylan treatment also decreased the concentrations of 12α-hydroxylated bile acids, and increased the levels of equol, indolepropionate, and eicosadienoic acid. This study indicated that the beneficial effects of arabinoxylan on T2D may be partially attributed to the modification of gut microbiota and related metabolites.