JP2007117031A - Fermented milk having interferon-gamma expression inducing action and fermented milk production spawn - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide fermented milk having new function of relation with I-type allergy clarified on scientific grounds, and to provide fermented milk production spawn to be used for producing the fermented milk. <P>SOLUTION: The fermented milk contains the fungus body or fungus body component of a plurality kinds of lactic acid bacteria composed of Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subsp. lactis, and Lactococcus lactis subsp. cremoris. It is possible to induce interferon-gamma expression and adjust Th1/Th2 balance to Th1 domination by daily eating the fermented milk. As a result of this, generation of IgE is inhibited to inhibit appearance of I type allergy. The fermented milk production spawn to be used for producing the fermented milk contains the lactic acid bacteria. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to fermented milk and inoculum, and more specifically, fermented milk containing interferon gamma expression-inducing action containing a plurality of specific types of lactic acid bacteria, and inoculum for fermented milk production used for producing the fermented milk About.

  In recent years, allergic diseases such as hay fever, atopic dermatitis, and asthma have been increasing and have become a global problem. These allergic diseases are caused by type I allergy, which is one of immediate allergies. The outline of the mechanism of occurrence of type I allergy is as follows. First, when an allergen causing antigen (allergen) enters the body, the allergen binds to immunoglobulin E (IgE) on the surface of mast cells. Allergen-bound mast cells degranulate and release chemical mediators such as histamine and leukotrienes. These chemical mediators cause type I allergies. It has been found that people with allergic diseases have higher IgE levels in the blood compared to healthy people.

  The outline of the production mechanism of IgE is as follows. First, when an antigen such as an allergen enters, an immunocompetent cell called a dendritic cell takes in the antigen and presents a part of the antigen on the cell surface. Next, naive T cells bind to the antigen presented on the cell surface and differentiate into Th1 or Th2 cells. Both Th1 cells and Th2 cells are activated helper T cells, each of which plays a different role. Th1 cells induce cytotoxic T cells and are involved in cellular immunity. On the other hand, Th2 cells activate B cells and are involved in antibody production, ie humoral immunity. The antibody is an immunoglobulin (Ig), and IgE, which is the main player of type I allergy, is also produced by Th2 cells. It has been found that various immune abnormalities occur when the balance between Th1 cells and Th2 cells (Th1 / Th2 balance) is disrupted. For example, when the Th1 / Th2 balance becomes Th2-dominant, antibody production is induced and a large amount of IgE is produced. That is, it can be said that type I allergy is a state in which the Th1 / Th2 balance is predominantly Th2. Therefore, from the viewpoint of suppressing type I allergy, it is preferable to adjust the Th1 / Th2 balance so that Th1 is dominant.

  Multiple cytokines are involved in whether naive T cells differentiate into Th1 cells or Th2 cells. That is, when interleukin-12 (IL-12) acts, it differentiates into Th1 cells, and when interleukin-4 (IL-4) acts, it differentiates into Th2 cells. In addition, in order for Th1 cells to induce cytotoxic T cells, the actions of interleukin-2 (IL-2) and interferon gamma (IFNγ) are required. On the other hand, the action of interleukin-4 (IL-4) and interleukin-10 (IL-10) is necessary for Th2 cells to activate B cells. Therefore, by increasing the expression level of IL-2 or IFNγ, the Th1 / Th2 balance can be adjusted predominantly by Th1. As a result, it is considered that the production of IgE is suppressed and the onset of type I allergy is also suppressed.

  In recent years, fermented milk represented by yogurt has been empirically said to be effective for hay fever and atopic dermatitis. However, there are few examples where the effect has been clarified with scientific evidence. In particular, there are very few examples of human clinical trials. In Patent Document 1, in a hay fever patient who orally ingested yogurt prepared using a strain of Lactobacillus paracasei, a kind of lactic acid bacteria, the ratio of Th1 cells is increased, It is described that the symptoms also tended to improve.

Kefir is known as fermented milk other than yogurt. Kefir is fermented milk that has been eaten for a long time in the Caucasus region, which is famous for its longevity. Traditional kefir is produced by adding inoculum called kefir grains to milk and fermenting it. In addition to a plurality of lactic acid bacteria, yeast is also included in this inoculum, and kefir is distinct from yogurt prepared by fermentation with one or two kinds of lactic acid bacteria. At present, a more active inoculum based on kefir grains has been developed and is already on the market.
JP 2005-137357 A

  According to a questionnaire survey, eating kefir results in reducing the symptoms of hay fever. However, the relationship between kefir and type I allergies such as hay fever has not yet been elucidated scientifically. It is considered that fermented milk having a new function can be developed by scientifically elucidating this relationship. An object of the present invention is to provide fermented milk having a new function whose relationship with type I allergy has been elucidated on a scientific basis, and an inoculum for producing fermented milk used in the production thereof.

  The invention described in claim 1 for solving the above-described problem is a plurality of Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremoris. It is fermented milk having an interferon gamma expression inducing action, which contains bacterial cells or bacterial cell components of various lactic acid bacteria.

  The present invention relates to fermented milk with a new function. That is, the fermented milk of the present invention has four types of lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subsp. Lactis. And Lactococcus lactis subsp. Cremoris cells or cell components, and has an interferon gamma expression inducing action. According to the fermented milk of the present invention, expression of interferon gamma can be easily induced by eating daily, and the Th1 / Th2 balance can be adjusted predominantly by Th1. As a result, the production of IgE can be suppressed and the onset of type I allergy can be suppressed. The fermented milk of the present invention may further contain other microorganisms in addition to the above-mentioned four types of lactic acid bacteria. Other microorganisms include lactic acid bacteria and yeasts other than the above four types. In addition, Lactococcus lactis may be simply referred to as Lactococcus lactis, and Lactococcus lactis may be simply referred to as Lactococcus cremoris.

  In other words, the fermented milk of the present invention, in other words, Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith It is an interferon gamma expression inducer or composition for inducing interferon gamma expression comprising a bacterial cell or a bacterial cell component, and is mainly used as a food or drink.

Invention of Claim 2 is fermented milk which has the interferon gamma expression induction effect of Claim 1 which contains 2 * 10 < ⁸ > or more microbial cells per gram per 1 type of lactic acid bacteria.

  The fermented milk of the present invention contains a certain number or more of four types of lactic acid bacteria. With this configuration, the expression of interferon gamma can be more reliably induced.

  The invention according to claim 3 is characterized in that a plurality of types of lactic acid bacteria comprising Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith are added to milk. The fermented milk having an interferon gamma expression inducing action obtained by fermenting milk by the action of the lactic acid bacteria.

  The fermented milk of the present invention comprises four kinds of lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith, in milk, It is produced by fermentation and has an interferon gamma expression inducing action. Even with the fermented milk of the present invention, the expression of interferon gamma can be easily induced by eating on a daily basis, and the Th1 / Th2 balance can be adjusted predominantly by Th1. As a result, the production of IgE can be suppressed and the onset of type I allergy can be suppressed.

  In other words, the fermented milk of the present invention, in other words, contains a plurality of lactic acid bacteria consisting of Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith. An interferon gamma expression inducer or composition for inducing interferon gamma expression, which is added to milk and fermented with the action of the lactic acid bacteria, and is mainly used as a food or drink.

  A structure having an action of reducing the serum IgE concentration or an action of suppressing an increase of the serum IgE concentration is also recommended (Claim 4). In other words, a configuration used as an IgE production inhibitor or an composition for suppressing IgE production is also recommended. In addition, a configuration having an action of suppressing type I allergy (claim 5) is also recommended. In other words, a configuration used as a type I allergy inhibitor or a composition for suppressing type I allergy is also recommended.

  The invention according to claim 6 is a fermented milk production inoculum containing a plurality of types of lactic acid bacteria, wherein the lactic acid bacteria are Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspices lactis, and It is an inoculum for fermented milk production for use in the production of fermented milk having the interferon gamma expression inducing action according to any one of claims 1 to 5, comprising Lactococcus lactis subspecies Cremolis.

  The present invention relates to an inoculum for producing fermented milk containing a plurality of types of lactic acid bacteria. The inoculum for producing fermented milk of the present invention is used for producing the fermented milk of the present invention, and includes four lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies. -Contains lactis and lactococcus lactis subspecies cremolith. According to the inoculum for producing fermented milk of the present invention, fermented milk having an interferon gamma expression inducing action can be produced simply and efficiently. In addition, the inoculum for fermented milk manufacture of this invention should just contain the above-mentioned 4 types of lactic acid bacteria, and may also contain other microorganisms. Other microorganisms include lactic acid bacteria and yeasts other than the above four types.

The invention described in claim 7 is the inoculum for producing fermented milk according to claim 6, which contains 2 × 10 ⁸ or more lactic acid bacteria per gram per one type of lactic acid bacteria.

  The inoculum of the present invention contains a certain number or more of the above four types of lactic acid bacteria. With this configuration, fermented milk having an interferon gamma expression inducing action can be more reliably produced.

  The invention according to claim 8 is the inoculum for producing fermented milk according to claim 6 or 7, which is formulated into granules.

  The inoculum for producing fermented milk of the present invention is formulated into granules. With this configuration, it can be added to milk more easily and reliably. Furthermore, the inoculum for producing fermented milk of the present invention is suitable for long-term storage.

  According to the fermented milk of the present invention, expression of interferon gamma can be easily induced by eating daily, and the Th1 / Th2 balance can be adjusted predominantly by Th1. As a result, the production of IgE can be suppressed and the onset of type I allergy can be suppressed.

  According to the inoculum for producing fermented milk of the present invention, fermented milk having an interferon gamma expression inducing action can be produced simply and efficiently.

  Hereinafter, the best mode for carrying out the present invention will be described in detail.

  One aspect of the fermented milk of the present invention is that of four lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremoris Contains body or fungal components. The fermented milk of the present invention only needs to contain all four types of lactic acid bacteria, and the ratio of each lactic acid bacterium is not particularly limited. Moreover, you may further contain microorganisms other than the said 4 types of lactic acid bacteria, for example, other lactic acid bacteria and yeast. “Bacteria” includes both live and dead bacteria. Furthermore, “cell component” includes all components such as cell walls derived from the cell.

  In addition, the fermented milk of this aspect is, in other words, Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis sub-species lactis, and Lactococcus lactis sub-species cremolith. It is an interferon gamma expression inducer or composition for inducing interferon gamma expression comprising a bacterial cell or a bacterial cell component, and is mainly used as a food or drink.

There is no limitation in particular as content of a microbial cell or a microbial cell component, Fermented milk should just have an interferon gamma expression induction effect. In a preferred embodiment, each lactic acid bacterium contains 2 × 10 ⁸ or more cells per gram.

  Other aspects of the fermented milk of the present invention include four lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremollis. And fermented milk produced by fermenting milk by the action of the lactic acid bacteria. As a result, the fermented milk produced by this method contains these four kinds of lactic acid bacteria and has an interferon gamma expression inducing action. The fermented milk of this aspect, in other words, contains a plurality of types of lactic acid bacteria consisting of Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith. An interferon gamma expression inducer or composition for inducing interferon gamma expression, which is added to milk and fermented with the action of the lactic acid bacteria, and is mainly used as a food or drink.

  The inoculum for producing fermented milk of the present invention contains four types of lactic acid bacteria, namely, Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith. . The inoculum for producing fermented milk of the present invention is used for producing the fermented milk of the present invention. The four lactic acid bacteria in the inoculum for producing fermented milk of the present invention can be obtained from various microorganism storage institutions, but commercially available inoculum can also be used. In the inoculum for producing fermented milk of the present invention, it is sufficient that all four types of lactic acid bacteria are included, and the ratio of each lactic acid bacterium is not particularly limited. Moreover, you may further contain microorganisms other than the said 4 types of lactic acid bacteria, for example, other lactic acid bacteria and yeast.

The content of the four lactic acid bacteria is not particularly limited as long as the fermented milk having an interferon gamma expression inducing action can be produced. In a preferred embodiment, each lactic acid bacterium contains 2 × 10 ⁸ or more lactic acid bacteria per gram.

  Examples of the inoculum for producing fermented milk of the present invention include pastes and freeze-dried products, but freeze-dried products are advantageous in terms of long-term storage. In a preferred embodiment, the inoculum for producing fermented milk is formulated into granules. As a formulation method, a commonly used method can be applied as it is. For example, it can be formulated by lyophilizing lactic acid bacteria together with appropriate excipients and stabilizers. For example, the highly active kefir (registered trademark) of Roselle, Canada, includes lactic acid bacteria such as Lactococcus diacetilactis and Leuconostoc cremoris in addition to these four lactic acid bacteria, and An inoculum containing yeast such as Saccharomyces florentinus and formulated into granules by freeze-drying. This highly active kefir can also be used as it is as a seed for producing fermented milk of the present invention.

  EXAMPLES The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

  The test in this example was commissioned to Osaka University Graduate School of Medicine and Osaka University Institute for Microbial Diseases.

1. Preparation of fermented milk 1 g of granule of highly active kefir bacteria (registered trademark, manufactured by Roselle, Canada, imported and sold by limited company Nakagaki engineer office) was added to 1 L of paper-packed milk (Meiji Dairies) and mixed. . The mixture was allowed to stand at 25 ° C. for 24 hours to prepare fermented milk (hereinafter referred to as “homemade kefir”). The prepared homemade kefir was stored at 4 ° C. In addition, when the acidity and pH of the prepared homemade kefir were measured three times, the acidity was 0.75%, 0.71%, and 0.83%, and the pH was 4.40, 4.55, and 4.23. Met.

2. Ingestion of Fermented Milk to Subjects Subjects were screened by measuring the concentration of cedar pollen-specific IgE in serum using a cedar pollen-specific IgE antibody measurement reagent (Mitsubishi Chemical Yatron). Fourteen males and females 20 years or older whose serum concentration of cedar pollen-specific IgE was 0.7 IU / mL or higher were selected as subjects. The attributes of the subjects are shown in Table 1.

  Seventeen subjects were divided into a home-made kefir intake group (hereinafter sometimes simply referred to as “kefir intake group”) and a milk intake group (control). Subjects in the homemade kefir intake group received 300 mL of homemade kefir per day for 3 consecutive weeks. During this period, other companies' yogurts, lactic acid bacteria beverages, and natto were not consumed. In addition, I did not take homemade kefir for the next 3 weeks. Blood was collected from peripheral blood before ingestion of homemade kefir (day 0), at 3 weeks of ingestion (21 days after the start of the test), and at 6 weeks (after 3 weeks of non-ingestion, on day 42 of the start of the test). Serum was prepared from the collected blood. On the other hand, seven subjects in the milk intake group (control) took milk in the same manner instead of home-made kefir. The test method, blood collection, serum preparation, etc. were performed in exactly the same manner as the homemade kefir intake group. For each serum prepared, the total IgE concentration and IFNγ concentration were measured. All measurements were performed using a dedicated ELISA kit (Medical and Biological Laboratories). Hereinafter, “total serum IgE concentration” is simply referred to as “serum IgE concentration”.

3. Measurement results of serum IFNγ concentration Table 2 shows the measurement results of serum IFNγ concentration. Note that “−” in Table 2 was determined to be an abnormal value and deleted. Furthermore, the graph produced based on the value of Table 2 is shown in FIGS. FIG. 1 is a line graph showing the relationship between the serum IFNγ concentration (average value) and the number of test days in each group. In FIG. 1, the vertical axis represents the serum IFNγ concentration (IU / mL), which is a relative value when the serum IFNγ concentration on day 0 is 1. The horizontal axis is the elapsed days. FIG. 2 is a bar graph in which each group is further divided into a mild group and a severe group, and the serum IFNγ concentration (average value) is compared. The subjects whose serum IgE concentration before ingestion of kefir was 200 to 400 IU / mL were defined as a mild group, and subjects whose serum IgE concentration was 400 IU / mL or more were defined as severe groups (the same applies hereinafter). FIG. 3 is a bar graph showing the result of FIG. 2 as an increase rate on the 21st day. The rate of increase (%) is calculated from the formula “(21st day value−0th day value) ÷ 0th day value × 100” (the same applies hereinafter).

  As shown in FIG. 1, in the milk intake group (control), the serum IFNγ concentration decreased to 0.83 times that of the 0th day (before intake) on the 21st day of the test, and even on the 42nd day of the test. It did not rise as much as 1.11 times before ingestion. On the other hand, in the kefir intake group, the serum IFNγ concentration on the 21st day of the test increased 1.16 times on the 0th day (before intake), and on the 42nd day of the test, it increased to 1.54 times before the intake. Was rising. As described above, serum IFNγ concentration was increased in the kefir intake group.

  As shown in FIG. 2 and FIG. 3, in the milk intake group (control), in the mild group, the serum IFNγ concentration on the 21st day from the start of the test shows almost no change in the serum IFNγ concentration on the 0th day (before intake) There was a slight downward trend. In the severe group, the serum IFNγ concentration on the 21st day from the start of the test was slightly higher than the serum IFNγ concentration on the 0th day (before ingestion). On the other hand, in the kefir intake group, the serum IFNγ concentration increased by 14% or more in both the mild group and the severe group (FIG. 3). From the above, serum IFNγ concentration was increased in hay fever patients who took homemade kefir.

4). Measurement results of serum IgE concentration Table 3 shows the measurement results of serum IgE concentration. Furthermore, the graph produced based on the value of Table 3 is shown in FIGS. FIG. 4 is a line graph showing the relationship between the serum IgE concentration (average value) and the test days in each group. In FIG. 4, the vertical axis represents the serum IgE concentration (IU / mL), which is a relative value when the serum IgE concentration on day 0 is 1. The horizontal axis is the elapsed days. FIG. 5 is a bar graph in which each group is further divided into a mild group and a severe group and the serum IgE concentration (average value) is compared. FIG. 6 is a bar graph showing the result of FIG. 5 as an increase rate on the 21st day.

  As shown in FIG. 4, in the milk intake group (control), the serum IgE concentration increased 1.12 times from the 0th day (before intake) on the 21st day of the test, and even on the 42nd day after the start of the test. There was no difference between before intake and almost the same value. On the other hand, in the kefir intake group, the serum IgE concentration on the 21st day of the test was 0.97 times that of the 0th day (before the intake), and 0.92 times that before the intake on the 42nd day of the test. That is, in the kefir intake group, an increase in serum IgE concentration was suppressed.

  As shown in FIGS. 5 and 6, in the milk intake group (control), the serum IgE concentration on the 21st day from the start of the test was the serum IgE on the 0th day (before intake) in both the mild group and the severe group. It was higher than the concentration. On the other hand, in the kefir intake group, in the mild group, the serum IgE concentration on the 21st day from the start of the test was lower than the serum IgE concentration on the 0th day (before intake). In the severe group, the serum IgE concentration on the 21st day from the start of the test was almost the same as the serum IgE concentration on the 0th day (before ingestion), and there was no change (FIG. 6). From the above, it was shown that in patients with pollinosis who took homemade kefir, the serum IgE concentration decreased or the increase in serum IgE concentration was suppressed.

  Several types of lactic acid bacteria were isolated from highly active kefir bacteria (registered trademark). The following tests were performed on four of them (hereinafter referred to as “lactic acid bacteria # 1”, “lactic acid bacteria # 2”, “lactic acid bacteria # 4”, and “lactic acid bacteria # 62”), and attempts were made to identify these lactic acid bacteria. .

1. Utilization of various substrates For lactic acid bacteria # 1 and lactic acid bacteria # 2, the utilization of various substrates was examined using the API50CHL kit. The results are shown in Table 4. In Table 4, “+” represents positive, “−” represents negative, and “w” represents weak positive. This result was consistent with the assimilation data of the substrates possessed by Lactobacillus casei and Lactobacillus plantarum.

With regard to lactic acid bacteria # 4 and lactic acid bacteria # 62, the assimilation properties of various substrates were examined using API Strep20. The results are shown in Table 5. In Table 5, “+” represents positive, “−” represents negative, and “w” represents weak positive. This result was consistent with substrate assimilability data possessed by Lactococcus lactis subsp. Cremoris and Lactococcus lactis subsp. Cremoris.

2. Base sequence of 16S rRNA gene Genomic DNA was isolated from each lactic acid bacterium. PCR was performed using these genomic DNAs as templates and the oligonucleotides shown in SEQ ID NOs: 1 and 2 as primer pairs, and a DNA fragment containing the 16S rRNA gene was amplified. The base sequence of each amplified DNA fragment was determined. The base sequence of the amplified DNA fragment derived from lactic acid bacteria # 1 is shown in SEQ ID NO: 3. The base sequence of the amplified DNA fragment derived from lactic acid bacteria # 2 is shown in SEQ ID NO: 4. The base sequence of the amplified DNA fragment derived from lactic acid bacteria # 4 is shown in SEQ ID NO: 5. The base sequence of the amplified DNA fragment derived from lactic acid bacteria # 62 is shown in SEQ ID NO: 6. Information on each base sequence obtained was searched in the NCBI database. As a result, lactic acid bacteria # 1, lactic acid bacteria # 2, and lactic acid bacteria # 4 were identified as Lactobacillus casei, Lactobacillus plantarum, and Lactococcus lactis subspices lactis, respectively. Lactic acid bacteria # 62 was not found in the database, but was found to be a lactic acid bacterium genetically very similar to lactic acid bacteria # 4. Based on the results of assimilation of various substrates shown above and the results of nucleotide sequence determination of 16S rRNA gene, lactic acid bacteria # 1 is Lactobacillus casei, lactic acid bacteria # 2 is Lactobacillus plantarum, and lactic acid bacteria # 4 is Lactococcus lactis. -Subspecies lactis and lactic acid bacteria # 62 were identified as Lactococcus lactis subspecies cremolith.

The INFγ expression-inducing action of the four identified lactic acid bacteria (hereinafter referred to as scientific names) was confirmed by an in vitro test using macrophage cells (U937 cells). First, each lactic acid bacterium was inactivated by heating. Next, U937 cells (1 × 10 ⁶ cells) were cultured in the presence of inactivated lactic acid bacteria (2 × 10 ⁷ cells). The IFNγ concentration in the medium was measured at 20 and 40 hours of culture. As a control, culturing was carried out in the same manner using Escherichia coli instead of lactic acid bacteria. A control was also set in which U937 cells were cultured in the same manner without adding anything. The test was performed twice and the average value was calculated. The results are shown in Table 6.

  A graph created based on the values in Table 6 is shown in FIG. FIG. 7 is a bar graph showing the IFNγ concentration (average value) in the culture medium when each lactic acid bacterium was used. FIG. 7 (a) shows the result at 20 hours of culture, and FIG. As shown in FIG. 7 (a), at the 20th hour of culture, the concentration of IFNγ was increased when L. plantarum was added. Furthermore, as shown in FIG. 7 (b), after 40 hours of culturing, other lactic acid bacteria, that is, Lactobacillus casei (L. casei), Lactococcus lactis subspices lactis (L. lactis subsp. lactis) and L. lactis subsp. cremoris also increased IFNγ concentration. In particular, when Lactococcus lactis subspecies lactis was added, the increase in IFNγ concentration was remarkable. In the control Escherichia coli, no increase in IFNγ concentration was observed. From the above, four types of lactic acid bacteria, namely Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith induce IFNγ expression in U937 cells. It has been shown.

The fungal composition in the highly active kefir fungus (seed fungus) used in Example 1 and the prepared homemade kefir (fermented milk) was examined. The results are shown in Table 6. The numerical values in Table 6 are the average values of the three specimens and are expressed as the number of viable bacteria per gram (cfu). "Lactococcus" includes both Lactococcus lactis subspecies lactis and Lactococcus lactis subspecies cremolith. As a result, the least active Lactobacillus casei was 2.0 × 10 ⁸ cells / g, and the total of all lactic acid bacteria was 1.4 × 10 ⁹ cells / g in the highly active kefir bacteria. On the other hand, in the homemade kefir, the least Lactobacillus casei was 3.6 × 10 ⁸ cells / g, and the total of lactic acid bacteria was 1.8 × 10 ⁹ cells / g.

It is a line graph showing the relationship between the serum IFNγ concentration (average value) and the test days in the kefir intake group and the milk intake group. It is the bar graph which divided the IFNγ concentration (mean value) in serum into the mild group and the severe group in the kefir intake group and the milk intake group. It is the bar graph which represented the result of FIG. 2 by the increase rate in the 21st day. It is a line graph showing the relationship between the serum IgE density | concentration (average value) and test days in a kefir intake group and a milk intake group. It is the bar graph which divided the serum IgE density | concentration (average value) into the mild group and the severe group further in the kefir intake group and the milk intake group. It is the bar graph which represented the result of FIG. 5 by the increase rate in the 21st day. The result of the in vitro test of Example 2 is represented, (a) is a bar graph showing the concentration of IFNγ at 20 hours of culture, and (b) is a bar graph showing the concentration of IFNγ at 40 hours of culture.

Claims (8)

  Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis sub-species lactis and Lactococcus lactis sub-species cremolith Fermented milk having an expression inducing action. The fermented milk having interferon gamma expression-inducing action according to claim 1, which contains 2 × 10 ⁸ or more cells per gram per lactic acid bacterium.   Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremoliths are added to milk, and the milk is fermented by the action of the lactic acid bacteria Fermented milk having interferon gamma expression-inducing action.   The fermented milk having an interferon gamma expression-inducing action according to any one of claims 1 to 3, which has an action of reducing serum IgE concentration or an action of suppressing an increase in serum IgE concentration.   The fermented milk having interferon gamma expression-inducing action according to any one of claims 1 to 4, which has an action of suppressing type I allergy.   A fermented milk producing inoculum containing a plurality of lactic acid bacteria, wherein the lactic acid bacteria are Lactobacillus casei, Lactobacillus plantarum, Lactococcus lactis subspecies lactis, and Lactococcus lactis subspecies cremolith An inoculum for producing fermented milk for use in the production of fermented milk having interferon gamma expression inducing action according to claim 1. The inoculum for fermented milk production according to claim 6, comprising 2 × 10 ⁸ or more lactic acid bacteria per gram per one lactic acid bacterium.   The inoculum for fermented milk production according to claim 6 or 7, which is formulated in a granular form.

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