JP7645056B2 - Composition for preventing or improving lifestyle-related diseases - Google Patents

Description

The present invention relates to a composition for preventing or improving lifestyle-related diseases, which contains curdlan having an average particle size of 30 μm or less as an active ingredient.

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 2001 as a gelling agent, stabilizer, and thickener, and has attracted attention as a very useful food ingredient in the food industry. 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 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 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, while β-glucans derived from grains, which have a repeating structure of β-1,3-bonds 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.

In addition, it has been found in recent years 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 shown in recent years that whole wheat barley, 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).

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.

JP 2006-109730 A

Kimura et al. PNAS, 2011, Kimura et al. Nature Commun, 2013 Miyamoto et al., PLoS One, 2018

The objective of the present invention is to provide a composition that uses safe substances to prevent or improve lifestyle-related diseases.

The inventors of the present application discovered that curdlan with an average particle size of 30 μm or less has the ability to improve the intestinal environment, and thus completed the present invention.

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 (1) to (5).
to provide.

The present invention can significantly increase short-chain fatty acids, which are metabolites of intestinal bacteria, and improve the intestinal environment. Furthermore, improving the intestinal environment improves systemic metabolism and immune function, and therefore has the effect of preventing lifestyle-related diseases.

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 Weight change Tissue weight Blood biochemistry data Fecal short-chain fatty acids (loading week 12) Fecal short-chain fatty acids (3rd week of loading) Fecal secretory IgA Intestinal microbiota analysis Intestinal microbiota analysis

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.

The improvement of the intestinal environment in this invention means that microbial fermentation is promoted by increasing the number of useful bacteria in the intestinal flora, and the intestinal environment is improved. 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.

The improvement of lipid metabolism in the present invention means improving the metabolic function of the whole body, for example, significantly improving blood glucose and total cholesterol levels.

Immunological improvement in the present invention refers to the control of intestinal mucosal immune function by improving the intestinal environment, for example, the control of secretory IgA production in the intestinal tract.

Anti-obesity also refers to the suppression of weight gain.

The present invention can promote an 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, etc., and 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.

In the present invention, the curdlan having an average particle size of 30 μm or less 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 manufacturing 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.

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 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.

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 exhibits the above-mentioned functions. When administered to humans, the dosage and frequency of administration 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.

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

The composition of the present invention can be used to produce foods such as luxury items, functional foods, nutritional supplements, and dietary supplements by a normal food production method, except for the step of incorporating the composition together with raw materials into the food. 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 the normal method of ingestion of such food. The amount of 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.

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

The effect of curdlan having an average particle size of 30 μm or less was examined by the following method.
Test Example 1
Breeding method and experimental protocol
The test diets were 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 microflora 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).

Body weight change <br/>The group that consumed finely ground curdlan showed a tendency to suppress weight gain compared to the control group, confirming that finely ground curdlan tends to have an anti-obesity effect (Figure 2).

Tissue weight : Fat tissue weight tended to decrease with the ingestion of finely ground curdlan compared to the control group (Fig. 3). Interestingly, the cecum weight was significantly higher in the group that ingested curdlan compared to the control group, and this tendency was even more pronounced in the group that ingested finely ground curdlan (Fig. 3). This suggests that intestinal microbial fermentation is promoted by the ingestion of finely ground curdlan in the intestinal tract.

Blood biochemistry data showed that blood glucose levels were significantly lower in the group that consumed finely ground curdlan compared to the control group (Figure 4).In addition, plasma total cholesterol levels were also significantly lower in the group that consumed finely ground curdlan (Figure 4).

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

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).

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 phylum Bacteroidetes and a decrease in the phylum Firmicutes and Proteobacteria 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 change was greater in the group that ingested finely ground curdlan, suggesting that the metabolism of finely ground curdlan is closely related to the intestinal microbiota. Interestingly, the phylum Verrucomicrobia and Deferribacteres were characteristically increased in the group that ingested finely ground curdlan (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.

This study demonstrated that ingesting 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, blood glucose and total cholesterol levels were significantly improved by ingesting curdlan with an average particle size of 30 μm or less, which is expected to have an effect of improving systemic metabolic function. Furthermore, it was confirmed that ingesting curdlan with an average particle size of 30 μm or less increases the production of intestinal bacterial metabolites and short-chain fatty acids, which is expected to improve metabolism starting from the intestinal environment.

In addition, in the analysis of the intestinal flora, a change in the distribution of the flora was observed following 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 caused a shift to a so-called anti-obesity type of intestinal flora, 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 via the improvement of the intestinal flora.

Based on the above, it is expected that the ingestion of curdlan with an average particle size of 30 μm or less will have an effect of improving 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 (4)

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. 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. 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 intended to reduce blood glucose levels and/or total cholesterol in plasma . 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 .