Lacticaseibacillus paracasei HP7 useful for gastrointestinal health with preventive or alleviative efficacy for functional dyspepsia and uses thereof

Abstract

The present invention relates to Lacticaseibacillus paracasei HP7 with preventive or alleviative efficacy for functional dyspepsia and uses thereof. The composition comprising the Lacticaseibacillus paracasei HP7 strain (accession number: KCTC 13143 BP) of the present invention as an active ingredient was confirmed to increase expression of intestinal tight junction genes, improve gastrointestinal peristalsis and gastric emptying effects, enhances gastric weight and gastric emptying levels associated with gastric emptying, and significantly increase blood hormone levels related to digestive activity, thereby improving dyspepsia.

Description

Lacticasei-Bacillus paracasei HP7, which aids gastrointestinal health through the prevention or improvement of functional dyspepsia, and its uses

[0001] The present invention relates to Lacticase Bacillus paracasei HP7 having efficacy in preventing or improving functional dyspepsia and the use thereof.

[0002] Functional dyspepsia is a functional dyspepsia that is not a pathological or organic lesion, and is defined as a condition involving various symptoms such as persistent or recurrent discomfort or pain localized to the upper abdomen. It is a disease that includes various symptoms occurring mainly in the upper abdomen, such as upper abdominal pain, burning, fullness, bloating, early satiety, nausea, vomiting, and belching.

[0003] Although patents have been disclosed regarding Lacticase Bacillus paracasei (Lactobacillus paracasei) HP7 isolated from kimchi for its agglutination activity against Helicobacter pylori and its effect of inhibiting gastric cell adhesion, it is not known to have an effect of preventing or improving functional dyspepsia.

[0004] Accordingly, while searching for a material that could prevent, treat, or improve functional dyspepsia, the inventors of the present invention confirmed that Lacticase Bacillus paracasei HP7 has the effect of improving functional dyspepsia and completed the present invention.

[0005] One objective of the present invention is to provide a food composition for improving indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0006] Another objective of the present invention is to provide a pharmaceutical composition for the prevention or treatment of indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0007] Another object of the present invention is to provide a method for preventing or treating functional dyspepsia, comprising a composition containing the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient for use in preventing or treating functional dyspepsia, the use of the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) for the preparation of a drug for preventing or treating functional dyspepsia, and administering the composition containing the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient to a subject who requires it.

[0008] One aspect of the present invention is to provide a food composition for improving indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0009] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may be one or more of the following: a live Lacticaseibacillus paracasei HP7 cell, a dead Lacticaseibacillus paracasei HP7 cell, a lysate thereof, a culture solution thereof, an extract of the strain, an extract of the strain, an extract of the lysate, and an extract of the culture solution.

[0010] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may increase the expression of one or more of the tight junction proteins ZO-1, OCLN, and CLDN1.

[0011] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may exhibit one or more of an increase in GASTRIN expression, an inhibition of GIP expression, and an inhibition of Peptide YY expression, and may increase the expression of one or more of 5-HT4R, ANO1, RYR3, and smMLCK.

[0012] In one embodiment of the present invention, the indigestion refers to functional indigestion rather than pathological or organic lesions, and includes various symptoms such as discomfort or pain localized to the upper abdomen that occur continuously or repeatedly, and may be a disease that includes various symptoms occurring mainly in the upper abdomen, such as upper abdominal pain, burning, fullness, bloating, early satiety, nausea, vomiting, and belching.

[0013] Another aspect of the present invention is to provide a pharmaceutical composition for the prevention or treatment of indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0014] In another aspect of the present invention, a method for preventing or treating functional dyspepsia is provided, comprising a composition containing the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient for use in preventing or treating functional dyspepsia, the use of the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) for the preparation of a drug for preventing or treating functional dyspepsia, and administering the composition containing the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient to a subject who requires it.

[0015] Compositions containing the strain of Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) of the present invention as an active ingredient can improve indigestion by increasing the expression of intestinal cell tight junction genes, improving digestive peristalsis and gastric emptying effects, improving gastric weight and gastric emptying levels related to gastric emptying, and significantly increasing blood hormones related to digestive activity.

[0016] Figure 1 shows the results of Experimental Example 1, which confirm the intestinal cell survival rate when treated with HP7 strain.

[0017] Figure 2 shows the results of Experimental Example 2, which are the results of the analysis of tight junction-related gene expression in the HP7 strain.

[0018] Figure 3 shows the results of Experimental Example 3, showing the difference in body weight among the test groups.

[0019] Figures 4 and 5 show the results of Experimental Example 4, which confirm the distance food traveled due to peristalsis of the digestive system (intestines).

[0020] Figures 6 and 7 show the results of Example 5, confirming the change in stomach weight and the effect of emptying the stomach.

[0021] Figure 8 shows the results of Example 6, which confirms the change in indicators related to digestive activity in the blood.

[0022] Figure 9 shows the results of Example 7, which confirms the changes in gastrointestinal indicators in the blood.

[0023] The present invention will be described below with reference to the drawings.

[0024] Figure 1 shows the results of Experimental Example 1, confirming the survival rate of intestinal cells treated with the HP7 strain, and Figure 2 shows the results of Experimental Example 2, showing the results of the analysis of tight junction-related gene expression of the HP7 strain. Through these experimental results, it can be seen that the Lacticaseibacillus paracasei HP7 strain increases the expression of tight junction genes in intestinal cells, thereby demonstrating the ability to improve functional dyspepsia, which is known to have a high correlation with intestinal leakage.

[0025] In addition, Figure 3 shows the results of Experimental Example 3, indicating the difference in body weight among test groups; Figures 4 and 5 show the results of Experimental Example 4, confirming the distance food traveled due to digestive (intestinal) peristalsis; and Figures 6 and 7 show the results of Example 5, confirming changes in stomach weight and gastric emptying effects. In addition, Figure 8 shows the results of Example 6, confirming changes in indicators related to digestive activity in the blood; and Figure 9 shows the results of Example 7, confirming changes in indicators related to the gastrointestinal tract in the blood. Through these results, the Lacticaseibacillus paracasei HP7 strain can improve digestive peristalsis and gastric emptying effects, improve stomach weight and gastric emptying levels related to gastric emptying, and significantly increase hormones in the blood related to digestive activity, thereby helping to prevent and improve functional dyspepsia and contribute to gastrointestinal health.

[0026]

[0027] One aspect of the present invention is to provide a food composition for improving indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0028] In the present invention, "improvement" refers to any action that at least reduces parameters related to the condition being treated, such as the severity of symptoms. In this case, the strain may be used to improve vascular health, either simultaneously with or separately from a therapeutic agent, either before or after the onset of the related disease.

[0029] The above-mentioned Lacticaseibacillus paracasei HP7 strain was selected from strains isolated from kimchi for its excellent inhibitory activity against Helicobacter pylori. It was deposited as Lactobacillus paracasei HP7 at the Korea Collection for Type Culture (KCTC) of the Korea Research Institute of Biotechnology and Bioengineering on October 31, 2016, under accession number KCTC 13143BP; however, as of January 1, 2024, the classification of the strain has changed due to the reclassification of the genus Lactobacillus based on whole-genome information (Ministry of Food and Drug Safety Announcement No. 2021-168, Korean Standards for Health Functional Foods No. 3. Individual Standards and Specifications, 2. Functional Ingredients, 2-51 Probiotics), Lacticaseibacillus paracasei paracasei) changed to HP7.

[0030] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may be one or more of the following: a live Lacticaseibacillus paracasei HP7 cell, a dead Lacticaseibacillus paracasei HP7 cell, a lysate thereof, a culture solution thereof, an extract of the strain, an extract of the strain, an extract of the lysate, and an extract of the culture solution.

[0031] The type of medium for culturing the above strain is not significantly limited, and an optimal known medium may be used. Specifically, MRS medium, TGY medium, BHI medium, M17 medium, etc. In addition, the pH of the medium is not significantly limited as long as it is within a range where the strain can be cultured, for example, about pH 4.5 to 7.0. The culture temperature for culturing the strain according to the present invention is also not significantly limited, for example, about 25 to 45°C.

[0032] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may increase the expression of one or more of the tight junction proteins ZO-1, OCLN, and CLDN1. Functional dyspepsia is known to have a high correlation with intestinal leakage, and the HP7 of the present invention can improve not only intestinal leakage but also functional dyspepsia, which is known to have a high correlation with intestinal leakage, by increasing the expression of one or more of the tight junction proteins ZO-1, OCLN, and CLDN1.

[0033] In one embodiment of the present invention, the Lacticaseibacillus paracasei HP7 may exhibit one or more of an increase in GASTRIN expression, inhibition of GIP expression, and inhibition of Peptide YY expression, and may increase the expression of one or more of 5-HT4R, ANO1, RYR3, and smMLCK. The HP7 of the present invention can improve digestive peristalsis and gastric emptying by significantly increasing the food transit distance compared to a group induced with dyspepsia, improve gastric weight and gastric emptying ratio related to gastric emptying, and significantly increase hormones in the blood related to digestive activity, thereby improving functional dyspepsia.

[0034] In one embodiment of the present invention, the indigestion refers to functional indigestion rather than pathological or organic lesions, and refers to various symptoms such as discomfort or pain localized to the upper abdomen that occur continuously or repeatedly. It may be a disease that includes various symptoms occurring mainly in the upper abdomen, such as upper abdominal pain, burning, fullness, bloating, early satiety, nausea, vomiting, and belching. As an example, it may refer to one or more of continuous or repeated upper abdominal pain, discomfort, upper abdominal burning, heartburn, early satiety, post-meal fullness, upper abdominal pressure, and upper abdominal bloating.

[0035] When the composition of the present invention is prepared as a food composition, in addition to the Lacticaseibacillus paracasei HP7 strain as an active ingredient, it may include ingredients that are typically added during food manufacturing, such as, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavorings. Examples of carbohydrates may be monosaccharides, e.g., glucose, fructose, etc.; disaccharides, e.g., maltose, sucrose, oligosaccharides, etc.; and polysaccharides, such as conventional sugars like dextrin, cyclodextrin, etc., and sugar alcohols such as xylitol, sorbitol, erythritol, etc. As flavorings, natural flavorings [taumartin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)] and synthetic flavorings (saccharin, aspartame, etc.) may be used.

[0036] In addition, the food composition of the present invention may contain various nutritional agents, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0037] These ingredients may be used independently or in combination, and the proportion of these additives may be selected in the range of more than 0 and less than or equal to 20 parts by weight per 100 parts by weight of the food composition of the present invention, but is not limited thereto.

[0038] The food composition of the present invention may be used as a food, food additive, beverage, beverage additive, fermented milk, health functional food, etc. When used as a food, food additive, beverage, beverage additive, or health functional food, it may be provided in the form of various food products, fermented milk, meat, beverages, chocolate, snacks, confectionery, pizza, ramen, other noodles, chewing gum, ice cream, alcoholic beverages, vitamin complexes, alcoholic beverages, or other health functional food formulations, but is not limited thereto.

[0039]

[0040] Another aspect of the present invention is to provide a pharmaceutical composition for the prevention or treatment of indigestion comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient.

[0041] As described above, the Lacticaseibacillus paracasei HP7 strain of the present invention can improve indigestion by increasing the expression of intestinal cell tight junction genes, improving digestive peristalsis and gastric emptying effects, improving gastric weight and gastric emptying levels related to gastric emptying, and significantly increasing blood hormones related to digestive activity.

[0042] In the present invention, "treatment" refers to any act in which symptoms of a vascular disease are improved or beneficially altered by the administration of the above composition.

[0043] In the present invention, "prevention" refers to any act of suppressing or delaying symptoms of vascular disease by administering the above composition.

[0044] The pharmaceutical composition according to the present invention comprises Lacticaseibacillus paracasei HP7 as an active ingredient and may further comprise a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is one that is commonly used in formulations and includes, but is not limited to, saline solution, sterile water, Ringer's solution, buffered saline, cyclodextrin, dextrose solution, maltodextrin solution, glycerol, ethanol, liposomes, etc., and may further include other conventional additives such as antioxidants and buffers as needed. Additionally, by additionally adding diluents, dispersants, surfactants, binders, lubricants, etc., the composition may be formulated into injectable formulations such as aqueous solutions, suspensions, and emulsions, or into pills, capsules, granules, or tablets. Regarding suitable pharmaceutically acceptable carriers and formulations, the composition may preferably be formulated according to each component using the methods disclosed in the literature of Remington. The pharmaceutical composition of the present invention is not subject to any particular restrictions on the formulation, but can be formulated into injectables, inhalants, topical skin preparations, etc.

[0045] The pharmaceutical composition of the present invention may be administered orally or parenterally (e.g., intravenously, subcutaneously, intraperitoneally, or topically) depending on the intended method, and the dosage may be appropriately selected by those skilled in the art, although it depends on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the time.

[0046] The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, a pharmaceutically effective amount refers to an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level may be determined based on factors including the patient's disease type and severity, drug activity, sensitivity to the drug, time of administration, route of administration and elimination rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field. Other pharmaceutical compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered as a single or multiple doses. It is important to administer an amount that obtains maximum effect with a minimum amount without side effects by considering all of the above-mentioned factors, and this can be easily determined by a person skilled in the art.

[0047] Specifically, the effective amount of the pharmaceutical composition of the present invention may vary depending on the patient's age, gender, condition, body weight, absorption rate, inactivation rate, and excretion rate of the active ingredient in the body, the type of disease, and concomitant drugs. Generally, 0.001 to 150 mg, preferably 0.01 to 100 mg per kg of body weight, may be administered daily or every other day, or divided into 1 to 3 doses per day. However, since the dosage may be increased or decreased depending on the route of administration, severity of obesity, gender, body weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

[0048]

[0049] In another aspect of the present invention, a composition is provided comprising the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient for use in preventing or treating functional dyspepsia.

[0050] Another aspect of the present invention provides the use of the Lacticaseibacillus paracasei HP7 strain (accession number: KCTC 13143BP) for the manufacture of a drug for the prevention or treatment of functional dyspepsia.

[0051] In another aspect of the present invention, a method for preventing or treating functional dyspepsia is provided, comprising administering a composition containing the strain Lacticaseibacillus paracasei HP7 (accession number: KCTC 13143BP) as an active ingredient to a subject who requires it.

[0052] One or more specific examples are described in more detail below through embodiments. However, these embodiments are intended to illustrate one or more specific examples and the scope of the present invention is not limited to these embodiments.

[0053]

[0054] Experimental Example 1: Confirmation of intestinal cell viability upon treatment with HP7 strain

[0055] To confirm the toxicity of intestinal cells upon treatment with the HP7 strain, the MTT (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay was conducted. Human colon cell line Caco-2 cells were placed in 96-cell plates at 1×10⁻³ 5 After culturing for 24 hours in cells / well, the control group Lacticaseibacillus paracasei ATCC 25302 1X10 7 CFU / well, Lacticasey-Bacillus paracasei HP7 1X10 7 CFU / well and 1X10 8After treatment with CFU / well, the culture was carried out for 24 hours. Subsequently, an MTT solution with a concentration of 0.5 mg / mL was prepared and added at 10% of the medium volume, followed by 4 hours of incubation. After incubation, the sample was centrifuged at 1,500 rpm for 5 minutes, the supernatant was removed, and 150 μL of DMSO was added to dissolve the formazan crystals, after which the absorbance was measured.

[0056] As confirmed in Figure 1, the measurement results showed that no change in cell viability was observed in the human colon cell line Caco-2 for the Lacticase Bacillus paracasei HP7 and Lacticase Bacillus paracasei ATCC 25302 strains, and it was confirmed that there was no effect on culture characteristics.

[0057]

[0058] Experimental Example 2: Confirmation of tight junction-related gene expression in HP7 strain

[0059] To analyze the expression of tight junction-related genes ZO-1 (Tight junction protein 1), OCLN (Occludin), and CLDN (Claudin-1) in the intestinal cell line of Lacticaseibacillus paracasei HP7, Caco-2 cells were plated in 1x10 12-cell plates. 5 Cells were cultured in cells / wells. Culture was carried out for 21 days for cell differentiation, and the medium was changed every 2 to 3 days. To the differentiated cells, the control group, *Lacticase-bacillus paracasei ATCC 25302 1X10 7 CFU / well, Lacticasey-Bacillus paracasei HP7 1X10 7 CFU / well and 1X10 8 CFU / well was treated and cultured for 2 hours, and TNF-α solution was treated to a concentration of 100 ng / mL and cultured for 24 hours.

[0060] Total RNA was extracted from cultured cells, and cDNA was synthesized using the Qiagen Omniscript Reverse Transcription Kit. The synthesized cDNA was analyzed using RT-PCR with the Taqman Gene Expression Assay, and gene expression levels were normalized using GAPDH.

[0061] As a result, as confirmed in Figure 2, the HP7 strain of the present invention showed a recovery and increase in the expression of tight junction-related genes even at the same concentration compared to the control group and the ATCC 25302 strain. Since functional dyspepsia is known to have a high correlation with intestinal leakage, we conducted an animal experiment on functional dyspepsia with the assumption that increasing the expression of tight junction-related genes would help alleviate and improve functional dyspepsia.

[0062]

[0063] Experimental Example 3: Confirmation of body weight changes by in vivo test group

[0064] In the present invention, the effect of preventing or improving functional dyspepsia by consuming Lacticaseibacillus paracasei HP7 was confirmed.

[0065] Mice were purchased from Dooyul Biotech Co., Ltd., and 6-week-old male Balb / c mice were used. The rearing room environment was set to a temperature of 22 ± 1 ℃, a humidity of 55 ± 10 %, and a lighting time of 12 hours. Mice were acclimatized for one week while being freely supplied with standard solid food and water.

[0066] A loperamide-induced functional dyspepsia model was used as the animal model. In a functional dyspepsia pathology model characterized by delayed gastric emptying induced by loperamide, it was confirmed that functional dyspepsia was alleviated by pretreatment with Lacticaseibacillus paracasei HP7 prior to loperamide administration. The animal experiments were divided into experiments measuring food transit distance and gastric emptying / emptying experiments.

[0067] The experimental group was composed of a normal group, a functional dyspepsia induction group (control group), a positive control group, and a probiotic administration group (HP7). On the day of the experiment, loperamide was administered intraperitoneally at a dose of 10 mg / kg to the functional dyspepsia induction group, the positive control group, and the probiotic administration group, while the normal group was administered saline solution in the same manner. The positive control group used Mosapride, a gastric motility enhancer known as a major treatment for functional dyspepsia. The HP7 experimental group received 1 x 10 for 2 weeks prior to loperamide administration. 8 , 1X10 9 It was administered orally at a dose of 200 µl / day, and the positive control, mosapride, was also administered orally at the same dose of 3 mg / kg.

[0068] As a result, as confirmed in Table 1 and Figure 3, no significant difference in body weight was found between the test groups, and no significant difference in dietary intake was found either.

[0069] Mouse weight (g)NormalControlMosaprideHP7 (CFU)10 8 10 9 24.3223.9123.4524.1623.0625.7124.0523.9624.5022.7325.3822.6524.9623.9525.0023.3525.2825.1827.7324.6223.7523.7124.0525.7324.6223.4924.7425.8222.9625.10

[0070]

[0071] Experimental Example 4: Verification of food movement distance by digestive system (intestine) peristalsis

[0072] On the day of the experiment, loperamide (10 mg / kg, induction of functional dyspepsia) was administered intraperitoneally. 30 minutes later, 200 μL of 5% activated charcoal dissolved in 10% gum arabic was orally administered to mice. 30 minutes later, mice were sacrificed at time intervals, and the distance traveled by the activated charcoal from the pylorus to the cecum was measured. The migration ratio was measured as the distance traveled by the activated charcoal relative to the total length from the pylorus to the cecum.

[0073] As a result, as confirmed in Figures 4 and 5, improved intestinal peristalsis was observed in mice administered Mosapride compared to mice administered Loperamide (Control), and mice administered the HP7 strain of the present invention showed superior food transport distance and transport rate compared to mice administered Mosapride. Through this, it can be seen that the HP7 strain of the present invention can improve gastrointestinal peristalsis in functional dyspepsia.

[0074]

[0075] Experimental Example 5: Confirmation of changes in stomach weight and gastric emptying effect

[0076] Loperamide (10 mg / kg, inducing functional dyspepsia) was administered intraperitoneally on the day of the experiment using the same method as the previously described experiment. After 30 minutes, 500 μL of phenol red solution (indicator) was orally administered to the mice. The phenol red solution was prepared by adding 0.05% (w / v) phenol red to distilled water containing 1.5% (w / v) carboxymethylcellulose. After 30 minutes of administering the phenol red solution, the mice were sacrificed sequentially at specific time intervals, gastric tissue was excised, and homogenized with 5 mL of 0.1N sodium hydroxide and 0.5 mL of 20% (w / v) trichloroacetic acid. The homogenate was centrifuged at 3,000 rpm for 20 minutes, and then 1 mL of the supernatant was added to 4 mL of 0.5N sodium hydroxide to measure the absorbance at 560 nm. In addition, blood was collected and serum was separated, and it was stored at -80°C until use along with some stomach and duodenal tissues.

[0077] After measuring the absorbance, the emptying rate was calculated using the following formula.

[0078]

[0079] Gastric emptying (%) = (1-X) / Y * 100

[0080] X: Absorbance of phenol red solution remaining in the stomach

[0081] Y: Absorbance of naive phenol red mixed with sodium hydroxide solution.

[0082]

[0083] As a result, as confirmed in Figure 6, in the group that induced indigestion with a liquid diet containing the ingested phenol red solution (indicator), gastric weight increased due to residual effect, whereas in the positive control group (mosapride) and HP7 intake group, gastric peristalsis was restored and gastric weight decreased.

[0084] In addition, as shown in Figure 7, the gastric emptying effect was measured by consuming a liquid diet containing a phenol red solution (indicator) and, 30 minutes later, sacrificing and opening the stomach, extracting the stomach, and measuring the absorbance of the indicator remaining in the stomach from the gastric tissue homogenate, and significant gastric emptying and gastric emptying effects were confirmed in the HP7 intake group.

[0085] Based on these results, the HP7 strain of the present invention has the effects of reducing gastric weight, gastric emptying, and gastric emptying, which can help improve functional digestive disorders.

[0086]

[0087] Experimental Example 6: Results of confirming changes in indicators related to digestive activity in the blood

[0088] As previously mentioned, hormonal indicators related to digestive activity were measured in isolated serum. Gastrin is produced in response to protein stimulation and is known to promote gastric motility and maintain the structure of the gastric mucosa. Ingestion of the HP7 strain significantly increased gastrin production compared to the control group administered loperamide. This suggests that it may contribute to gastric emptying and emptiness by promoting gastrointestinal motility.

[0089] GIP is a gastric inhibitory polypeptide that inhibits gastric motility and gastric acid secretion while promoting insulin secretion. It is also known to inhibit gastrin production and suppress gastric acid secretion and gastric motility. PYY, peptide YY, functions to regulate insulin secretion, inhibit gastric acid secretion, and inhibit gastric emptying; it delays the time it takes for food to move from the mouth to the cecum, thereby inducing a feeling of fullness after meals. As confirmed in Figure 8, the intake of the HP7 strain was found to significantly reduce GIP and PYY, which inhibit gastric motility or gastric emptying, compared to the control group administered loperamide. This suggests that, similar to promoting gastrin production, it may contribute to gastric emptying and emptying by improving gastrointestinal motility.

[0090]

[0091] Experimental Example 7: Results of confirming changes in gastrointestinal-related indicators in the blood

[0092] Gastrointestinal emptying is carried out by gastrointestinal motility mediated by the autonomic nervous system, but functional dyspepsia is induced in the control group administered loperamide. The 5-HT and its receptor (5-HT4R) genes are involved in smooth muscle movement, and mosapride, used as a positive control, is known to be a gastric motility enhancer that directly affects 5-HT4R.

[0093] Smooth muscle contraction-related genes 5HT4R (5-hydroxytryptamine(serotonin) receptor 4), ANO1 (anoctamin-1), RYR3 (ryanodine receptor 3), and smMLCK (smooth muscle cell myosin light chain kinase) were analyzed using gastric pylorus tissue. Total RNA was extracted from a portion of the gastric pylorus tissue of sacrificed mice, and cDNA was synthesized using the Qiagen Omniscript Reverse Transcription Kit. The synthesized cDNA was analyzed using RT-PCR with the Taqman Gene Expression Assay, and gene expression levels were normalized using GAPDH.

[0094] As a result, as confirmed in Figure 9, it was confirmed that the HP7 administration group, like the positive control group, restored the gene expression of 5-HT4R, thereby contributing to the improvement of digestive function, and it was also confirmed that the gene expression of ANO1, RYR3, and smMLCK, which are related to smooth muscle contraction, was significantly increased. Through these results, the HP7 strain of the present invention can improve digestive function by promoting gastrointestinal motility through smooth muscle motility improvement.

[0095]

[0096] The present invention has been described above with reference to its preferred embodiments. Those skilled in the art will understand that the present invention may be embodied in modified forms without departing from the essential characteristics of the invention. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the invention is defined by the claims, not by the foregoing description, and all variations within the scope of the claims should be interpreted as being included in the invention.

[0097]

[0098] [Consignment Number]

[0099] Depository Name: Korea Research Institute of Biotechnology and Bioengineering Biological Resource Center (KCTC)

[0100] Trustee Number: KCTC13143BP

[0101] Date of Trust: 20161031

[0102]

[0103] [Deposit Certificate]

[0104]

Claims

1. A food composition for improving functional dyspepsia comprising the strain Lacticaseibacillus paracasei HP7 (Deposit No.: KCTC 13143BP) as an active ingredient.

2. In Paragraph 1, The above Lacticaseibacillus paracasei HP7 is a food composition for preventing or improving functional dyspepsia, comprising one or more of the following: Lacticaseibacillus paracasei HP7 live cells, Lacticaseibacillus paracasei HP7 dead cells, a lysate thereof, a culture solution thereof, an extract of the strain, an extract of the strain, an extract of the lysate, and an extract of the culture solution.

3. In Paragraph 1, A food composition for improving functional dyspepsia in which the above-mentioned Lacticaseibacillus paracasei HP7 increases the expression of one or more of the tight junction proteins ZO-1, OCLN, and CLDN1.

4. In Paragraph 1, The above Lacticaseibacillus paracasei HP7 exhibits one or more of the increase in GASTRIN expression, the inhibition of GIP expression, and the inhibition of Peptide YY expression, and A food composition for improving functional dyspepsia that increases the expression of one or more of 5-HT4R, ANO1, RYR3, and smMLCK.

5. In Paragraph 1, The above functional dyspepsia is a food composition for improving functional dyspepsia that suppresses one or more of the following: upper abdominal pain, discomfort, upper abdominal burning, heartburn, early satiety, post-meal fullness, upper abdominal pressure, and upper abdominal bloating.

6. A pharmaceutical composition for the prevention or treatment of functional dyspepsia comprising the strain Lacticaseibacillus paracasei HP7 (Deposit No.: KCTC 13143BP) as an active ingredient.

7. A composition comprising the strain Lacticaseibacillus paracasei HP7 (Deposit No.: KCTC 13143BP) as an active ingredient for use in the prevention or treatment of functional dyspepsia.

8. Use of the strain Lacticaseibacillus paracasei HP7 (Accession No.: KCTC 13143BP) for the manufacture of a drug for the prevention or treatment of functional dyspepsia.

9. A method for preventing or treating functional dyspepsia, comprising administering a composition containing the strain Lacticaseibacillus paracasei HP7 (Deposit No.: KCTC 13143BP) as an active ingredient to a subject who requires it.

Images