A single administration of barley ß-glucan and arabinoxylan extracts reduces blood glucose levels at the second meal via intestinal fermentation.

Diet with barley may suppress the glycemic response after consuming the next meal ("second meal effect"). This study aimed to investigate the second meal effect and its mechanism. Mice were given a single dose of ß-glucan or arabinoxylan, the primary sources of soluble fiber in barley. A single dose of ß-glucan or arabinoxylan extract, followed 6 h later by a 20% glucose solution (second meal), suppressed blood glucose elevation. Arabinoxylan and ß-glucan increased the levels of short-chain fatty acids (SCFAs) in the ileum and cecum, respectively. Total GLP-1 secretion in the blood increased with ß-glucan and showed an increasing trend with arabinoxylan. These results suggest barley ß-glucan and arabinoxylan are fermented in the intestinal tract to generate SCFAs, which may induce GLP-1 secretion and control blood glucose levels during the second meal.

Effects of Daily Kelp (Laminaria japonica) Intake on Body Composition, Serum Lipid Levels, and Thyroid Hormone Levels in Healthy Japanese Adults: A Randomized, Double-Blind Study.

To investigate whether supplementation with iodine-reduced kelp (Laminaria japonica) powder decreases body fat composition in overweight Japanese subjects, a randomized, double-blind, placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥25 and <30 kg/m2. Subjects were randomly assigned to consume thirty tablets/d (10 tablets orally, 3 times/d) containing either iodine-reduced kelp powder (test, 6 g kelp powder corresponding to 3 g alginate/d) or kelp-free powder (placebo) for 8 weeks. Anthropometric measurements, blood lipids, and serum thyroid hormone levels were obtained before and after the trial. Body fat percentage was significantly decreased in male subjects from the test group compared with the placebo group. The same tendency was observed for body weight (p = 0.065) and BMI (p = 0.072) in male subjects. No significant changes in anthropometric measurements or visceral fat area were observed in female subjects. Serum thyroid hormone concentrations did not increase after 1.03 mg/d of iodine supplementation through kelp intake. The intake of iodine-reduced kelp powder led to significant and safe reductions in body fat percentage in overweight male subjects. The consumption of kelp high in alginate may contribute to preventing obesity without influencing thyroid function in Japanese subjects with a relatively high intake of iodine from seaweed.

Effects of Whole Grain Wheat Bread on Visceral Fat Obesity in Japanese Subjects: A Randomized Double-Blind Study.

Metabolic syndrome is a risk factor for cardiovascular diseases and has become increasingly common in Japan. Epidemiological studies show inverse associations between intake of whole wheat grains and metabolic syndrome, but few dietary intervention trials have investigated the effect of whole wheat grain consumption. It was investigated whether a diet in which refined wheat bread (RW diet) was substituted by whole grain wheat bread (WW diet) would reduce visceral fat obesity in Japanese subjects. A randomized double-blind placebo-controlled intervention study was conducted in 50 Japanese subjects with body mass index (BMI) ≥ 23 kg/m2. Subjects were randomly assigned WW (WW group) or RW diets (RW group) for 12 weeks. Blood samples and computed tomography scans were obtained every 6th week. The WW group showed decrease (-4 cm2) in visceral fat area (VFA) (p < 0.05), whereas the RW group showed no significant changes. These time-dependent changes were significantly different between the groups. WW diet led to significant and safe reductions in VFA in subjects with BMI ≥ 23 kg/m2. WW diet may contribute to preventing visceral fat obesity.

[Milk, Daily products and Bone health.Characteristics of calcium in milk.]

Milk contains approximately 110mg of calcium per 100mL of milk, a good source of dietary calcium. The calcium in milk comprises of calcium caseinate, micellar calcium phosphate and soluble calcium. It is also reported that the calcium in milk has an excellent bioavailability. Intervention studies of Japanese women have shown that the absorption rate of calcium in milk was greater than that found in small fish and vegetables. Factors taken into account as contributing to higher absorption rates of calcium in milk were:1)the types of calcium present(caseinate, micellar, soluble), 2)the presence of lactose which promotes calcium absorption, and 3)the presence of casein-phosphopeptide which increases soluble calcium fraction. Higher solubility was also observed in the small intestine of rats fed a micellar calcium phosphate casein-phosphopeptide(MCP-CPP)complex prepared from milk compared to that in rats fed insoluble whey calcium.

Effects of liquid konjac on parameters related to obesity in diet-induced obese mice.

Konjac-mannan has been suggested to exert a protective effect against visceral obesity. However, there is little knowledge about the effects of liquid konjac (LK) that is partially alkali gelled. The purpose of the present work was to evaluate the potential beneficial effects of a LK powder on obesity in mice. Male C57BL/6J mice were fed a high-fat diet supplemented with either 2.5 or 5% LK powder for 80 days. Growth parameters, abdominal fat content, serum biochemical markers, and hepatic lipid accumulations were measured. Dietary supplementation with LK resulted in decreased body weight gain and abdominal fat accumulation. Dose-dependent decreases were observed in accumulation of hepatic lipids and serum total cholesterol, leptin, insulin concentrations. The study findings indicated that LK had preventing effect against obesity, including the reduction of abdominal and hepatic lipid accumulation and serum parameters related to obesity.

A short-term ingestion of fructo-oligosaccharides increases immunoglobulin A and mucin concentrations in the rat cecum, but the effects are attenuated with the prolonged ingestion.

We examined the effects of fructo-oligosaccharides (FOS) on IgA and mucin secretion in the rat cecum after different ingestion periods. Rats were fed a control diet or a diet containing FOS for 1, 2, 4, and 8 wk. FOS ingestion greatly increased IgA and mucin concentrations at 1 and 2 wk, but the effects were disappeared or attenuated at 4 and 8 wk. After 1 wk, FOS induced higher lactobacilli and lactate concentrations and lower cecal pH in the cecum, but the alterations were moderated with the prolonged ingestion accompanying with increasing short-chain fatty acid concentrations. At 1 and 2 wk, FOS increased IgA plasma cells and polymeric immunoglobulin receptor expression in the cecal mucosa and strongly depressed fecal mucinase activities related to the lower cecal pH. These findings may explain the FOS-induced early elevation of IgA and mucin. Clearly, FOS effects on IgA and mucin secretion considerably differ depending on the ingestion period.

Effect of cooked white rice with high ß-glucan barley on appetite and energy intake in healthy Japanese subjects: a randomized controlled trial.

White rice is a dominant grain-based food in Japan, but excess intake of polished rice may cause obesity. Barley is a grain-based food, similar to white rice, but it has the potential to control appetite and reduce energy intake. We investigated the effect of cooked white rice with high ß-glucan barley on appetite and energy intake. The study was conducted as a randomized crossover design with twenty-one healthy Japanese women [mean ± standard deviation body mass index (BMI) 23.3 ± 0.7 kg/m(2)]. Subjects consumed a breakfast of cooked white rice with high ß-glucan barley (BAR) or white rice (WR), followed by an ad libitum lunch and dinner. Energy intake was measured at the lunch and the dinner using plate waste. Subjects' perception scores on hunger, fullness, satiety, and prospective food consumption were assessed using a visual analogue scale (VAS) before and after the breakfast, lunch and dinner. BAR significantly reduced the VAS scores of hunger and prospective food consumption, and increased fullness before lunch compared to WR (P = 0.032, 0.019 and 0.038, respectively). Energy intake at lunch and the cumulative energy intake (lunch + dinner) subsequent to BAR consumption were significantly lower than WR (P = 0.035 and 0.021, respectively). BAR was able to modulate appetite and reduce energy intake. The combination of white rice with high ß-glucan barley could play a beneficial role in preventing and treating obesity and other obesity-related metabolic diseases.

Barley consumption under a high-fat diet suppresses lipogenic genes through altered intestinal bile acid composition.

We evaluated whether barley flour consumption in a high-fat environment affects lipid metabolism through signals mediated by bile acids. Four-week-old mice were fed a high-fat diet supplemented with cellulose (HC) or ß-glucan-rich barley flour (HB) for 12 weeks. Bile acid composition in the intestinal tract and feces was measured by GC/MS. Gene expression levels involved in bile acid metabolism in the liver and intestinal tract were determined by RT-PCR. Similar parameters were measured in mice treated with antibiotics (antibiotics-cellulose [AC] and antibiotics-barley [AB]) to reduce the activity of intestinal bacteria. The Results showed that the HB group had lower liver blood cholesterol and triglyceride levels than the HC group. The HB group showed a significant decrease in primary bile acids in the gastrointestinal tract compared to the HC group. On the other hand, the concentration of secondary bile acids relatively increased in the cecum and feces. In the liver, Fxr activation suppressed gene expression levels in synthesizing bile acids and lipids. Furthermore, in the gastrointestinal tract, Tgr5 was activated by increased secondary bile acids. Correspondingly, AMP levels were increased in the HB group compared to the HC group, AMPK was phosphorylated in the liver, and gene expression involved in lipid synthesis was downregulated. A comparison of the AC and AB groups treated with antibiotics did not confirm these effects of barley intake. In summary, our results suggest that the prevention of lipid accumulation by barley consumption involves signaling through changes in bile acid composition in the intestinal tract.

Low-methoxyl pectin stimulates small intestinal mucin secretion irrespective of goblet cell proliferation and is characterized by jejunum Muc2 upregulation in rats.

Generally, soluble fibers increase small intestinal mucin secretion by increasing the number of goblet cells in a viscosity-dependent manner. The present study aimed to examine the mechanism by which low-methoxyl pectin (LPC) affects mucin secretion in the small intestine. First, diets containing 50 g/kg of low-viscosity fiber (LPC, gum arabic, guar gum, low-molecular konjac mannan, arabinogalactan, sodium alginate) or high-molecular konjac mannan (KMH) were fed to Wistar rats for 10 d. Luminal mucin was greater in the LPC and KMH groups than in the fiber-free control group, but only the KMH group had more goblet cells in the ileum compared with the other groups. Next, Sprague-Dawley rats were fed LPC, KMH, or high-methoxyl pectin (HPC) diets (50 g/kg) for 10 d. The KMH and LPC groups, but not the HPC group, had greater luminal mucin than the control group, whereas jejunum Muc2 expression was higher only in the LPC group. Sprague-Dawley rats fed the LPC diet for 1 or 3 d had greater luminal mucin and jejunum Muc2 expression than those fed the control diet. In vitro studies using HT-29MTX cells showed that, of the various fibers studied, only LPC and HPC affected mucin secretion. Finally, Wistar rats were fed the LPC diet with or without neomycin in drinking water for 10 d; neomycin treatment did not compromise the effect of LPC on mucin secretion. We conclude that LPC does not affect the number of goblet cells but can interact directly with the epithelium and stimulate small intestinal mucin secretion.

Effects of paramylon-rich Euglena gracilisEOD-1 powder on visceral fat obesity in moderately obese Japanese adults: A randomized, double-blind, placebo-controlled, parallel-group trial.

To investigate whether supplementation of paramylon (PM)-rich Euglena gracilis EOD-1 powder (EOD-1) reduces visceral fat obesity in moderately obese Japanese subjects. A randomized, double-blind, placebo-controlled intervention study was conducted involving 36 Japanese adults with a body mass index (BMI) ≥25 and <30 kg/m2. Subjects were randomly assigned into two groups to consume EOD-1 capsules (EOD-1 group, 2.6 g PM/day) or cellulose capsules (placebo group) for a 12-week period. Anthropometric measurements including visceral fat area (VFA) and blood samples were measured at baseline and throughout the trial. There was no significant difference in VFA between the two groups, although subgroup analysis by gender showed a significant decrease in VFA in the male EOD-1 group compared with the placebo group. Serum adiponectin levels in all subjects from the EOD-1 group were significantly higher than in the placebo group. By comparison with the placebo group, the subjects in the EOD-1 group showed a significant reduction in serum HbA1c levels. EOD-1 intake led to a significant reduction in VFA in male subjects with moderate obesity (BMI 25-30 kg/m2). PM in EOD-1 may contribute to preventing visceral fat obesity in male Japanese subjects. Moreover, PM may also contribute to improving glucose homeostasis in moderately obese Japanese adults.

Small intestinal goblet cell proliferation induced by ingestion of soluble and insoluble dietary fiber is characterized by an increase in sialylated mucins in rats.

The study aimed to examine the effects of insoluble and soluble fibers on mucin sialylation and sulfation in the small intestine. First, diets containing soluble [konjac mannan (KM), psyllium, or guar gum; 50 g/kg) or insoluble (polystyrene foam, wheat bran, or cornhusk; 80 g/kg) fiber were fed to rats for 13 d. The fiber-fed groups had more goblet cells in the ileum than the fiber-free control group. High-iron diamine/alcian blue staining showed more sialylated mucin-producing cells in the fiber-fed groups than in the control, whereas sulfated mucin-producing cells were fewer (insoluble fibers) or unchanged (soluble fibers). Second, feeding KM (50 g/kg) and beet fiber (BF) (80 g/kg) diets for 7 d yielded a higher ileum Siat4C expression than the control, but Gal3ST2 and Gal3ST4 expression was comparable. Luminal mucin content correlated with sialic acid (r = 0.96; P < 0.001) or sulfate (r = 0.62; P < 0.01), but the slope of the sialic acid-derived equation was greater than that of the sulfate-derived equation, indicating a preferred increase in sialylated mucins. Third, rats were fed the control diet for 10 d while receiving antibiotic treatment. Analysis of the luminal mucin showed that sialylated mucins were more vulnerable to bacterial degradation than sulfated mucins. Finally, a study of bromo-deoxyuridine incorporation in rats fed a BF diet indicated that goblet cell proliferation accompanied by increased sialylated mucin appeared to be related to accelerated ileal epithelial cell migration. We conclude that intestinal goblet cell responses to insoluble and soluble fibers are characterized by increases in sialylated mucin production.

Arabinoxylan as well as ß-glucan in barley promotes GLP-1 secretion by increasing short-chain fatty acids production.

Barley is rich in soluble dietary fiber including ß-glucan and arabinoxylan. Barley ß-glucan is fermented by gut bacteria and, thereby contributes to an effect on intestinal bacterial composition and short-chain fatty acids (SCFAs). It also increases GLP-1 secretion via SCFAs receptor. However, few studies have focused on barley arabinoxylan. Therefore, we have investigated the effects of arabinoxylan from barley on intestinal fermentability and GLP-1 secretion. C57BL/6J mice were fed a high-fat diet containing arabinoxylan-dominant barley flour without ß-glucan (bgl) and high ß-glucan-containing barley flour (BF) for 12 weeks. We conducted oral glucose tolerance test (OGTT) to measure insulin and GLP-1 concentrations. The concentration of SCFAs in the cecum contents was also determined. Furthermore, we measured mRNA expression assay GLP-1 secretion using real-time PCR. The OGTT result showed that GLP-1 concentrations at 60 min were increased in mice fed bgl and BF. Acetic acid and total SCFAs concentrations in the cecum contents were increased in both the barley groups, and butyric acid was increased in the bgl group. Furthermore, the bgl and BF groups had increased Gpr43, a receptor for SCFAs, and NeuroD which is involved in L cell differentiation. These results show arabinoxylan as well as ß-glucan is involved in the SCFAs-mediated increase in GLP-1 secretion upon barley consumption.

Consumption of barley flour increases gut fermentation and improves glucose intolerance via the short-chain fatty acid receptor GPR43 in obese male mice.

Barley consumption is expected to increase insulin sensitivity by increasing the level of short-chain fatty acids (SCFAs) and promoting the secretion of GLP-1. However, the involvement of GPR43, a receptor for SCFAs, has not been investigated. Therefore, we evaluated whether the inhibitory effect of ß-glucan-rich barley intake on blood glucose rise is mediated by GPR43 signalling via an increase of SCFAs. C57BL/6J mice and GPR43-knockout mice were fed high-fat diets with either cellulose (HC) or ß-glucan-rich barley flour (HB) for 12 weeks. The level of SCFAs in cecum contents was measured and the concentration of GLP-1 in the portal vein was determined. The supernatant of the cecum contents of C57BL/6J mice was added to GLUTag cells, and then the changes to GLP-1 and intracellular Ca2+ concentrations determined. The same parameters were measured using cells in which GPR43 was knocked down by siRNA. C57BL/6J mice fed HB diets showed a suppressed glucose rise compared to those on the HC diet. Cecum SCFAs and GLP-1 concentration in the portal vein were also increased by the HB diet. When an aqueous solution from the cecum content of mice fed a HB diet was added to GLUTag cells, GLP-1 secretion and intracellular Ca2+ concentration were increased. These phenomena were not observed in cells with knockdown of GPR43. In GPR43 knockout mice an increase of GLP-1 in the portal vein and suppression of blood glucose elevation was attenuated, despite increased SCFAs brought on by the HB diet. In conclusion, GPR43 activation in the intestinal tract via increased SCFAs is required for the glucose intolerance-improving effect of barley consumption.

Beta-Glucan in Foods and Health Benefits.

Many articles and manuscripts focusing on the structure, function, mechanism of action, and effects of ß-glucan have been published recently [...].

High ß-Glucan Barley Supplementation Improves Glucose Tolerance by Increasing GLP-1 Secretion in Diet-Induced Obesity Mice.

The aim of this study was to investigate the underlying mechanism for the improvement of glucose tolerance following intake of high ß-glucan barley (HGB) in terms of intestinal metabolism. C57BL/6J male mice were fed a fatty diet supplemented with HGB corresponding to 5% of dietary fiber for 83 days. An oral glucose tolerance test was performed at the end of the experimental period. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC-MS (gas chromatography-mass spectrometry). The mRNA expression levels related to L cell function in the ileum were measured by real-time PCR. Glucagon-like peptide-1 (GLP-1) levels in the portal vein and cecal content were assessed by enzyme-linked immunosorbent assay. GLP-1-producing L cells of the ileum were quantified by immunohistochemistry. HGB intake improved glucose tolerance and increased the cecal levels of SCFAs, acetate, and propionate. The number of GLP-1-positive L cells in the HGB group was significantly higher than in the control group. GLP-1 levels in the portal vein and cecal GLP-1 pool size in the HGB group were significantly higher than the control group. In conclusion, we report improved glucose tolerance after HGB intake induced by an increase in L cell number and subsequent rise in GLP-1 secretion.

Microarray Analysis of Paramylon, Isolated from Euglena Gracilis EOD-1, and Its Effects on Lipid Metabolism in the Ileum and Liver in Diet-Induced Obese Mice.

We previously showed that supplementation of a high fat diet with paramylon (PM) reduces the postprandial glucose rise, serum total and LDL cholesterol levels, and abdominal fat accumulation in mice. The purpose of this study was to explore the underlying mechanism of PM using microarray analysis. Male mice (C57BL/BL strain) were fed an experimental diet (50% fat energy) containing 5% PM isolated from Euglena gracilis EOD-1 for 12 weeks. After confirming that PM had an improving effect on lipid metabolism, we assessed ileal and hepatic mRNA expression using DNA microarray and subsequent analysis by gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results suggested that dietary supplementation with PM resulted in decreased abdominal fat accumulation and serum LDL cholesterol concentrations via suppression of the digestion and absorption pathway in the ileum and activation of the hepatic PPAR signaling pathway. Postprandial glucose rise was reduced in mice fed PM, whereas changes in the glucose metabolism pathway were not detected in GO classification and KEGG pathway analysis. PM intake might enhance serum secretory immunoglobulin A concentrations via promotion of the immunoglobulin production pathway in the ileum.

Ingestion of High ß-Glucan Barley Flour Enhances the Intestinal Immune System of Diet-Induced Obese Mice by Prebiotic Effects.

The prebiotic effect of high ß-glucan barley (HGB) flour on the innate immune system of high-fat model mice was investigated. C57BL/6J male mice were fed a high-fat diet supplemented with HGB flour for 90 days. Secretory immunoglobulin A (sIgA) in the cecum and serum were analyzed by enzyme-linked immunosorbent assays (ELISA). Real-time PCR was used to determine mRNA expression levels of pro- and anti-inflammatory cytokines such as interleukin (IL)-10 and IL-6 in the ileum as well as the composition of the microbiota in the cecum. Concentrations of short-chain fatty acids (SCFAs) and organic acids were analyzed by GC/MS. Concentrations of sIgA in the cecum and serum were increased in the HGB group compared to the control. Gene expression levels of IL-10 and polymeric immunoglobulin receptor (pIgR) significantly increased in the HGB group. HGB intake increased the bacterial count of microbiota, such as Bifidobacterium and Lactobacillus. Concentrations of propionate and lactate in the cecum were increased in the HGB group, and a positive correlation was found between these organic acids and the IL-10 expression level. Our findings showed that HGB flour enhanced immune function such as IgA secretion and IL-10 expression, even when the immune system was deteriorated by a high-fat diet. Moreover, we found that HGB flour modulated the gut microbiota, which increased the concentration of SCFAs, thereby stimulating the immune system.

Macrophages rely on extracellular serine to suppress aberrant cytokine production.

A growing body of evidence indicates that cellular metabolism is involved in immune cell functions, including cytokine production. Serine is a nutritionally non-essential amino acid that can be generated by de novo synthesis and conversion from glycine. Serine contributes to various cellular responses, but the role in inflammatory responses remains poorly understood. Here, we show that macrophages rely on extracellular serine to suppress aberrant cytokine production. Depleting serine from the culture media reduced the cellular serine content in macrophages markedly, suggesting that macrophages depend largely on extracellular serine rather than cellular synthesis. Under serine deprivation, macrophages stimulated with lipopolysaccharide showed aberrant cytokine expression patterns, including a marked reduction of anti-inflammatory interleukin-10 expression and sustained expression of interleukine-6. Transcriptomic and metabolomics analyses revealed that serine deprivation causes mitochondrial dysfunction: reduction in the pyruvate content, the NADH/NAD+ ratio, the oxygen consumption rate, and the mitochondrial production of reactive oxygen species (ROS). We also found the role of mitochondrial ROS in appropriate cytokine production. Thus, our results indicate that cytokine production in macrophages is tightly regulated by the nutritional microenvironment.

Role of central leptin signaling in renal macrophage infiltration.

Monocytes/macrophages are key mediators of wound repair, tissue remodeling, and inflammation. However, the molecular mechanisms underlying macrophage recruitment to the site of inflammation is not fully understood. Leptin acts directly on the hypothalamus, thereby regulating food intake and energy expenditure. The leptin receptor, a single transmembrane protein that belongs to the gp130 family of cytokine receptor superfamily, is expressed not only in the hypothalamus but in a variety of peripheral tissues, suggesting the role of leptin as a pro-inflammatory adipocytokine in peripheral tissues. Here, we show that deficiency of leptin signaling reduces renal macrophage infiltration after unilateral ureteral obstruction (UUO). Bone marrow transplantation studies using leptin signaling-deficient db/db mice revealed that leptin signaling in bone marrow cells may not play a major role in the UUO-induced renal macrophage infiltration. Interestingly, central leptin administration reverses the otherwise reduced UUO-induced renal macrophage infiltration in leptin-deficient ob/ob mice. This is effectively abolished by central co-administration of SHU9119, a melanocortin-3 receptor/melanocortin-4 receptor antagonist. This study demonstrates that central leptin administration in ob/ ob mice accelerates renal macrophage infiltration through the melanocortin system, thereby suggesting that the central nervous system, which is inherent to integrate information from throughout the organism, is able to control peripheral inflammation.

Low Molecular Weight Barley ß-Glucan Affects Glucose and Lipid Metabolism by Prebiotic Effects.

We investigated the effect of low molecular weight barley ß-glucan (LMW-BG) on cecal fermentation, glucose, and lipid metabolism through comparisons to high molecular weight ß-glucan (HMW-BG). C57BL/6J male mice were fed a moderate-fat diet for 61 days. LMW-BG or HMW-BG was added to the diet corresponding to 4% ß-glucan. We measured the apparent absorption of fat, serum biomarkers, the expression levels of genes involved in glucose and lipid metabolism in the liver and ileum, and bacterial counts of the major microbiota groups using real time PCR. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC/MS. Significant reductions in serum leptin, total- and LDL-cholesterol concentrations, and mRNA expression levels of sterol regulatory element-binding protein-1c (SREBP-1c) were observed in both BG groups. HMW-BG specific effects were observed in inhibiting fat absorption and reducing abdominal deposit fat, whereas LMW-BG specific effects were observed in increasing bacterial counts of Bifidobacterium and Bacteroides and cecal total SCFAs, acetate, and propionate. mRNA expression of neurogenin 3 was increased in the LMW-BG group. We report that LMW-BG affects glucose and lipid metabolism via a prebiotic effect, whereas the high viscosity of HMW-BG in the digestive tract is responsible for its specific effects.