Composition for preventing or improving lifestyle-related diseases

Abstract

To provide compositions that prevent or improve lifestyle-related diseases using safe substances.SOLUTION: The inventors of the present application have found the function of promoting intestinal microbial fermentation in curdlan having an average particle size of 30 μm or less, and have completed the present invention. The present invention can significantly increase short-chain fatty acids, which are intestinal bacterial metabolites, to prepare the intestinal environment. In addition, the improvement of the intestinal environment improves systemic metabolism or immune function, and thus also has an effect of preventing lifestyle-related diseases.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition for preventing or ameliorating lifestyle-related diseases, which comprises curdlan having an average particle size of 30 μm or less as an active ingredient. [Background technology]

[0002] Curdlan is a non-digestible polysaccharide produced outside the cells of microorganisms (such as bacteria Agrobacterium and Alcaligenes) by fermentation. It has the property of solidifying when heated (curdle), and was approved as a food additive in the food industry in 2001 as a gelling agent, stabilizer, and thickener, and has attracted attention as a very useful food material. Furthermore, finely ground curdlan, which has been processed to a fine average particle size, has improved water retention and elasticity compared to unprocessed curdlan, and is therefore expected to be an excellent food improver in terms of food processing properties (Patent Document 1). Curdlan is also known as a β-1,3-glucan with a pure linear structure due to β-(1→3) glycosidic bonds. β-glucans are polysaccharides consisting only of glucose, and some of them have been reported to exhibit several functions as water-soluble dietary fibers depending on the bond type. For example, β-glucans derived from fungi and seaweed, which have a β-1,3-1,6-bond as their main structure, have been shown to have antitumor effects, and β-glucans derived from cereals, which have repeating β-1,3- and β-1,4-bonds in their main chain, have been suggested to be related to the prevention of lifestyle-related diseases such as coronary artery disease and diabetes.

[0003] In recent years, it has been found that intestinal bacterial metabolites, short-chain fatty acids, exert an anti-obesity effect via host receptors (Non-Patent Document 1).In addition, it has been revealed that whole barley flour, which is rich in β-glucan, a type of dietary fiber, suppresses high-fat diet-induced obesity by increasing the production of short-chain fatty acids in the intestine and the associated appetite suppressing effect, as well as improving insulin sensitivity (Non-Patent Document 2).

[0004] However, it was not previously known that curdlan with an average particle size of 30 μm or less could prevent or improve lifestyle-related diseases. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2006-109730 A [Non-patent literature]

[0006] [Non-Patent Document 1] Kimura et al. PNAS, 2011, Kimura et al. Nature Commun, 2013 [Non-Patent Document 2] Miyamoto et al., PLoS One, 2018 Summary of the Invention [Problem to be solved by the invention]

[0007] An objective of the present invention is to provide a composition that uses safe substances to prevent or ameliorate lifestyle-related diseases. [Means for solving the problem]

[0008] The present inventors have discovered that curdlan with an average particle size of 30 μm or less has the function of improving the intestinal environment, and have completed the present invention.

[0009] The present invention relates to (1) A composition for preventing and improving lifestyle-related diseases, comprising curdlan having an average particle size of 30 μm or less as an active ingredient; (2) The composition according to (1), wherein the prevention and improvement of lifestyle-related diseases is improvement of intestinal environment. (3) The composition according to (1), wherein the prevention and improvement of lifestyle-related diseases is improvement of lipid metabolism. (4) The composition according to (1), wherein the prevention or improvement of lifestyle-related diseases is improvement of immunity. (5) The composition according to (1), wherein the prevention or improvement of lifestyle-related diseases is anti-obesity. (6) A food product comprising the composition according to any one of (1) to (5). to provide. Effect of the Invention

[0010] According to the present invention, it is possible to significantly increase short-chain fatty acids, which are metabolites of intestinal bacteria, and improve the intestinal environment. In addition, the improvement of the intestinal environment improves systemic metabolism or immune function, and therefore has the effect of preventing lifestyle-related diseases. [Brief description of the drawings]

[0011] [Figure 1] The effect of ingestion (also indicated as "loading" in the figure; the same applies to the following figures) of curdlan with an average particle size of 30 μm or less (indicated as MicroCurdlan in the figure; the same applies to the following figures) on metabolic function [Diagram 2] Weight change [Diagram 3] tissue weight [Figure 4] Blood biochemistry data [Diagram 5] Fecal short chain fatty acids (loading week 12) [Figure 6] Fecal short-chain fatty acids (3rd week of loading) [Figure 7] Fecal secretory IgA [Figure 8] Intestinal microbiota analysis [Figure 9] Intestinal microbiota analysis DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] Prevention and improvement of lifestyle-related diseases in the present invention refers to improvement of the intestinal environment, improvement of lipid metabolism, improvement of immunity, anti-obesity, etc., and particularly preferably refers to improvement of the intestinal environment.

[0013] The improvement of the intestinal environment in the present invention means that the intestinal environment is improved by promoting microbial fermentation through an increase in beneficial bacteria in the intestinal flora, etc. This microbial fermentation promotes the production of short-chain fatty acids, etc., and has the effect of improving sugar and lipid metabolism starting from the intestinal environment.

[0014] Improvement of lipid metabolism in the present invention means improvement of systemic metabolic function, for example, significant improvement of blood glucose level and total cholesterol level.

[0015] In the present invention, improving immunity refers to the regulation of intestinal mucosal immune function by improving the intestinal environment, and refers to, for example, the control of secretory IgA production in the intestinal tract.

[0016] Moreover, anti-obesity refers to suppression of weight gain.

[0017] The present invention can promote the increase in the production of intestinal bacterial metabolites and short-chain fatty acids and improve the intestinal environment by changing the distribution of intestinal flora through an increase in beneficial bacteria, and by promoting a shift to a so-called anti-obesity type of flora. In addition, the improvement of the intestinal environment improves systemic metabolism and immune function, and therefore has the effect of preventing lifestyle-related diseases.

[0018] The curdlan having an average particle size of 30 μm or less in the present invention is preferably pulverized to an average particle size of 30 μm or less, more preferably 10 to 30 μm, using, for example, an airflow pulverizer such as a jet mill or a freeze pulverizer. For example, it can be obtained using the production method disclosed in JP-A-2006-109730. There are no particular limitations on the type of curdlan used as a raw material, and any commonly used polysaccharide consisting of water-insoluble β-1,3-glucan can be used.

[0019] In order to obtain the effects of the present application, the curdlan having an average particle size of 30 μm or less is administered as it is, or a composition containing it as an active ingredient. The composition of the present invention can be used as an agent for improving the intestinal environment, improving lipid metabolism, improving immunity, anti-obesity, etc., by adding other materials such as maltitol, sorbitol, starch, etc., which serve as excipients or diluents. The method of administration of the composition of the present invention is not particularly limited, but oral administration is preferred. Specifically, it can be administered in the form of oral preparations such as tablets, powders, granules, pills, suspensions, emulsions, infusions / decoctions, capsules, syrups, liquids, elixirs, extracts, tinctures, and liquid extracts.

[0020] In the present invention, the dosage of curdlan having an average particle size of 30 μm or less is not particularly limited as long as it is an amount that can express the above-mentioned functions. The dosage and frequency of administration when administered to humans vary depending on the administration form, age, weight, etc. of the recipient, but it is usually administered once or several times a day so that an adult receives 300 mg to 30 g, preferably 500 mg to 15 g, and particularly preferably 1 g to 10 g of curdlan having an average particle size of 30 μm or less per day.

[0021] The administration interval is not particularly limited, but it is preferable to administer continuously. Usually, it is 1 day to 1 year, preferably 1 week to 3 months. The composition of the present invention can be used not only for humans but also for animals other than humans (non-human animals).

[0022] The composition of the present invention can be used for producing foods such as luxury items, functional foods, nutritional supplements, and supplements by a normal food production method except for the step of adding the composition to food together with raw materials. The food thus obtained is a normal food except for the fact that it contains curdlan with an average particle size of 30 μm or less, and can be consumed by a normal method for ingestion of such foods. The amount of the food to be consumed is preferably an amount that allows the intake of usually 300 mg to 30 g, preferably 500 mg to 15 g, and particularly preferably 1 g to 10 g of curdlan with an average particle size of 30 μm or less. EXAMPLES

[0023] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples.

[0024] The effect of curdlan with an average particle size of 30 μm or less was examined by the following method. Test Example 1 Breeding methods and experimental protocols The test diet was based on a high-fat diet (D12492; Research Diets Inc.) and contained 10% (w / w) of cellulose (control group, Fujifilm Wako Pure Chemical Industries, Ltd., mean particle size 38 μm), curdlan (regular product) (control group, Mitsubishi Corporation Life Sciences, mean particle size 104 μm), and finely ground curdlan (Mitsubishi Corporation Life Sciences, mean particle size 24 μm). Four-week-old male C57BL / 6J mice were fed each test diet for 12 weeks, and the metabolic improvement and obesity suppression effects in high-fat diet-induced obesity were confirmed (total of 3 groups, n = 10; Figure 1). Body weight was tracked over the course of the week, and changes in the weights of metabolic organs, various metabolic indicators in the blood, and intestinal flora at the end of the study were examined. For statistical analysis, each data was shown as the mean ± standard error. One-way analysis of variance was followed by the Tukey-Kramer method. The statistical significance level was set at p < 0.05. In the meta-16S gut microbiota analysis, the False Discovery Rate (FDR) correction in multiple comparisons was evaluated using the Benjamini & Hochberg method (q-value) (q < 0.05). EXAMPLES

[0025] Weight change The group that consumed finely ground curdlan showed a tendency to suppress weight gain compared to the control group, confirming the tendency of finely ground curdlan to exhibit an anti-obesity effect (Figure 2). EXAMPLES

[0026] tissue weight The weight of adipose tissue showed a tendency to decrease with the ingestion of finely ground curdlan compared to the control group (Fig. 3). Interestingly, the weight of the cecum was significantly higher in the group that ingested curdlan compared to the control group, and a more pronounced tendency was observed in the group that ingested finely ground curdlan (Fig. 3). This suggests that in the intestinal tract, intestinal microbial fermentation is promoted with the ingestion of finely ground curdlan. EXAMPLES

[0027] Blood biochemistry data measurement Blood glucose levels were significantly lower in the group that consumed finely ground curdlan compared to the control group (Figure 4). Furthermore, total plasma cholesterol levels were also significantly lower in the group that consumed finely ground curdlan (Figure 4). EXAMPLES

[0028] Fecal short chain fatty acids The short-chain fatty acids in the feces, which are metabolites of intestinal bacteria, were measured. As a result, the levels of acetic acid, propionic acid, and butyric acid in the feces of the group that had been given finely ground curdlan were significantly higher than those of the control group (Figure 5). Moreover, the production profile of these short-chain fatty acids already showed a similar tendency three weeks after the start of the dietary load (Figure 6). EXAMPLES

[0029] Fecal secretory IgA The effect of ingestion of finely ground curdlan on the intestinal mucosal immune system was first evaluated using fecal sIgA concentration as an indicator.The results showed that the group that had ingested the finely ground curdlan showed a significant increase in sIgA production compared to the control group (Figure 7). EXAMPLES

[0030] Intestinal microbiota analysis Next, to compare the intestinal environment, meta-16S intestinal microbiota analysis was performed using a next-generation sequencer. First, the distribution of microbiota was examined by principal component analysis, and it was confirmed that the intestinal microbiota of the group that ingested finely ground curdlan was different from that of the control group (Fig. 8; upper left). Next, as a result of comparison at the phylum level, an increase in the Bacteroidetes phylum and a decrease in the Firmicutes and Proteobacteria phylum were observed in both the group that ingested curdlan and the group that ingested finely ground curdlan compared to the control group (Fig. 8; lower left). The large change in the group that ingested finely ground curdlan suggested that the metabolism of finely ground curdlan is closely related to the intestinal microbiota. Interestingly, the group that ingested finely ground curdlan showed a characteristic increase in the Verrucomicrobia and Deferribacteres phylum (Fig. 8; lower left). In addition, a comparison of the gut microbiota at the family level showed that, among the increased Bacteroidetes phylum, the relative occupancy rate of the Bacteroidales S24-7 group family was significantly higher in the group fed finely ground curdlan compared to the control group (Fig. 8; right). On the other hand, compared to the control group, the Streptococcaceae family and Clostridiales Family XIII family were significantly decreased in the group fed finely ground curdlan compared to the control group (Fig. 8; right). On the other hand, no significant change was observed in the Alcaligenaceae family, which includes curdlan-producing bacteria, in the group fed finely ground curdlan.

[0031] This verification showed that the ingestion of curdlan with an average particle size of 30 μm or less had an anti-obesity effect, suggesting that curdlan with an average particle size of 30 μm or less may contribute to improving the intestinal environment. In addition, the ingestion of curdlan with an average particle size of 30 μm or less significantly improved blood glucose and total cholesterol levels, suggesting that it is expected to have an effect of improving systemic metabolic function. Furthermore, the ingestion of curdlan with an average particle size of 30 μm or less was confirmed to increase the production of intestinal bacterial metabolites and short-chain fatty acids, suggesting that metabolic improvement originating from the intestinal environment can be expected.

[0032] In addition, in the analysis of the intestinal flora, changes in the distribution of the flora were observed with the ingestion of curdlan with an average particle size of 30 μm or less. In fact, the ingestion of curdlan with an average particle size of 30 μm or less shifted the intestinal flora to a so-called anti-obesity type, so it is speculated that the ingestion of curdlan with an average particle size of 30 μm or less may have a systemic metabolic improvement effect through the improvement of the intestinal flora. [Industrial Applicability]

[0033] From the above, it is expected that the ingestion of curdlan with an average particle size of 30 μm or less will improve the intestinal environment of the host. It is expected that the use of curdlan with an average particle size of 30 μm or less will lead to the development of beneficial food ingredients aimed at preventing lifestyle-related diseases such as obesity and diabetes.

Claims

1. An anti-obesity composition for preventing and improving lifestyle-related diseases, comprising curdlan having an average particle size of 30 μm or less as an active ingredient.

2. A composition for preventing and improving lifestyle-related diseases, which contains curdlan having an average particle size of 30 μm or less as an active ingredient and is used to increase one or more of acetic acid, propionic acid, and butyric acid, which are metabolic products of intestinal bacteria.

3. A composition for preventing and improving lifestyle-related diseases, which contains curdlan having an average particle size of 30 μm or less as an active ingredient, and is useful for lowering blood glucose levels and / or lowering total cholesterol in plasma.

4. A food product for anti-obesity containing curdlan having an average particle size of 30 μm or less, for increasing one or more of the intestinal bacterial metabolic products of acetic acid, propionic acid and butyric acid, or for reducing blood glucose levels and / or total cholesterol in plasma.

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