WO2022191093A1

WO2022191093A1 - Composition for regulating gastric motor function

Info

Publication number: WO2022191093A1
Application number: PCT/JP2022/009581
Authority: WO
Inventors: 俊広大津
Original assignee: 株式会社明治
Priority date: 2021-03-08
Filing date: 2022-03-07
Publication date: 2022-09-15
Also published as: CN116940247A; JPWO2022191093A1

Abstract

The present invention elucidates the effect that the ingestion of lactic acid imparts on gastric motility. The present invention addresses the problem of providing a composition that is capable of improving post-meal delayed gastric emptying, and regulating the emptying rate to the duodenum. Provided is a composition for regulating gastric motor function that includes lactic acid bacteria belonging to the genus Lactobacillus and has 16S rRNA genes having the base sequence in SEQ ID NO: 1 and a sequence identity of 90% or more.

Description

Composition for adjusting gastric motility function

The present invention relates to a composition for adjusting gastric motility function containing specific lactic acid bacteria as an active ingredient.

The digestive tract plays an important role in the digestion and absorption of food. In recent years, it has been reported that lactic acid bacteria and their dead cells are effective for improving stomach-related symptoms.

For example, Patent Document 1 discloses a gastrin production inhibitor containing dead cells of Lactobacillus gasseri but not viable cells, added to a food composition, and The gastrin production inhibitor is proposed to be used for increasing the cell concentration of dead cells of Lactobacillus gasseri to 2×10 ¹⁰ cells/g or more. Patent Document 2 describes that when a person infected with H. pylori and a person taking a gastric acid secretion inhibitor ingests a composition containing a specific lactic acid bacterium for a certain period of time, the feeling of heavy stomach feeling is reduced and abdominal distension does not depend on eradication of H. pylori. Based on the fact that the reduction of gastroesophageal feeling and the improvement of subjective symptoms of gastroesophageal reflux disease that occurs without gastric acid secretion were observed, acid reflux-related symptoms and/or motor impairment with specific lactic acid bacteria as an active ingredient The above functional food is proposed to improve symptoms. In Patent Document 3, when a person with H. pylori-negative functional gastrointestinal disorders ingested a composition containing specific lactic acid bacteria for a certain period of time, a decrease in Bifidobacteria in the stomach and an increase in Prevotella bacteria in the stomach were observed. Based on this, we propose an upper gastrointestinal flora-improving agent containing the lactic acid bacterium as an active ingredient. Patent Document 4 discloses that specific lactic acid bacteria are used as an active ingredient, based on experimental results showing that the expression level of the ghrelin gene in stomach tissue increased when mice were fed yogurt containing specific lactic acid bacteria or the specific lactic acid bacteria. An anorexia ameliorating agent is proposed. Patent Document 5 discloses that when a patient with functional dyspepsia ingests a composition containing a specific lactic acid bacterium for a certain period of time, the occupancy rate of Bacteroidetes/Proteobacteria in the stomach is reduced, and the occupancy rate of Acidobacteria in the stomach. On the basis of the increase in the lactic acid bacteria, a gastric flora-improving agent containing the lactic acid bacterium as an active ingredient is proposed.

WO2012/102277 (Patent No. 6002582) WO2015/129281 (Patent No. 6781887) WO2017/221799 WO2018/012578 (Patent No. 6813974) WO2018/124003

As mentioned above, it has been reported that the intake of lactic acid bacteria is effective in improving stomach-related symptoms and gastric flora, but the effect of lactic acid bacteria on gastric motility is unclear.

When food is ingested, the fundus actively relaxes to accept the ingested food, which is then ground up by contraction of the antrum and the porridge is expelled through the pylorus into the duodenum. (gastric emptying).

The present inventors have found that continuous intake of specific lactic acid bacteria can improve delay in postprandial gastric emptying and adjust the rate of emptying into the duodenum, and completed the present invention.

The present invention provides the following.
[1] A composition for regulating gastric motor function, comprising a lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more, preferably 98% or more sequence identity with the nucleotide sequence of SEQ ID NO:1.
[2] The composition according to 1, wherein the gastric motility modulation is at least one of improving delayed gastric emptying and suppressing excessive gastric emptying rate.
[3] The composition according to 1 or 2, wherein the lactic acid bacterium belongs to the same species as Lactobacillus gasseri OLL2716 (FERM BP-6999).
[4] The composition according to any one of 1 to 3, wherein the lactic acid bacterium is Lactobacillus gasseri OLL2716 (FERM BP-6999).
[5] The composition according to any one of [1] to [4], for ingesting 1.0×10 ⁹ CFU or more of lactic acid bacteria per day.
[6] The composition according to any one of items 1 to 5, for ingesting 2×10 ⁷ CFU or more of lactic acid bacteria per dose.
[7] The composition according to any one of 1 to 6, which is fermented milk.
[8] The composition according to any one of 1 to 7, comprising Lactobacillus delbrueckii subspecies bulgaricus and Streptococcus thermophilus.
[9] The composition according to any one of 1 to 8, which is to be ingested continuously for 4 weeks or longer.
[10] The composition according to any one of items 1 to 9, which is to be ingested by a person who has mild to moderate gastric emptying delay and may feel stomach upset.
[11] The composition according to any one of 1 to 9, which is to be ingested by a person having a maximum gastric emptying rate of 20% dose/hr or more.
[12] A lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more, preferably 98% or more sequence identity with the nucleotide sequence of SEQ ID NO: 1. Composition for reduction.
[13] The composition according to 12, which is for any one selected from the group consisting of treatment of stomach upset, treatment of stomach pain, treatment of nausea, and appetite enhancement.
[14] A method for any selected from the group consisting of treating gastric upset, treating gastric pain, treating nausea, and increasing appetite by reducing peak gastric emptying rate.

The present invention also provides the following.
[1] Having a 16S rRNA gene belonging to the genus Lactobacillus and having 90% or more, preferably 98% or more sequence identity with the nucleotide sequence of SEQ ID NO: 1, for use in a method for regulating gastric motility A composition comprising lactic acid bacteria. Lactobacillus belonging to the genus Lactobacillus and having a 16S rRNA gene having a sequence identity of 90% or more, preferably 98% or more with the nucleotide sequence of SEQ ID NO: 1, in the production of a composition that regulates the gastric motility function, use. The step of administering to a subject a composition containing a lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more, preferably 98% or more sequence identity with the base sequence of SEQ ID NO: 1. How to coordinate motor function.
[2] The composition, use, or method according to 1, wherein the regulation of gastric motility is at least one of improving delayed gastric emptying and suppressing excessive gastric emptying rate.
[3] The composition, use or method according to 1 or 2, wherein the lactic acid bacterium belongs to the same species as Lactobacillus gasseri OLL2716 (FERM BP-6999).
[4] The composition, use, or method according to any one of 1 to 3, wherein the lactic acid bacterium is Lactobacillus gasseri OLL2716 (FERM BP-6999).
[5] The composition, use, or method according to any one of items 1 to 4, for ingesting 1.0×10 ⁹ CFU or more of lactic acid bacteria per day.
[6] The composition, use, or method according to any one of 1 to 5, for ingesting 2×10 ⁷ CFU or more of lactic acid bacteria per dose.
[7] The composition, use, or method according to any one of 1 to 6, which is fermented milk.
[8] The composition, use, or method of any one of 1 to 7, comprising Lactobacillus delbrueckii subspecies bulgaricus and Streptococcus thermophilus.
[9] The composition, use, or method according to any one of 1 to 8, for continuous ingestion for 4 weeks or more.
[10] The composition, use, or method of any one of 1 to 9, for ingestion by a person who has mild to moderate delayed gastric emptying and who may experience stomach upset.
[11] The composition, use, or method according to any one of 1 to 9, for ingestion by a person having a maximum gastric emptying rate of 20% dose/hr or more.
[12] A lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more, preferably 98% or more sequence identity with the nucleotide sequence of SEQ ID NO: 1. Compositions, uses or methods for reduction.
[13] The composition, use, or method according to 12, which is for any one selected from the group consisting of treatment of stomach upset, treatment of stomach pain, treatment of nausea, and appetite enhancement.
[14] A method, use for any selected from the group consisting of treating gastric upset, treating gastric pain, treating nausea, and increasing appetite by reducing peak gastric emptying rate; or method.

The composition of the present invention regulates gastric motility. The composition of the present invention also achieves at least one of improved delayed gastric emptying and reduced excessive gastric emptying rate.

Effect of continuous intake of LG21 in the per-protocol group (a) ΔTmax-AUC within the intake period: For each subject, the X axis is the intake elapsed period (week), and the Y axis is ΔTmax (min). The ΔTmax after one week and the ΔTmax after 12 weeks of ingestion were plotted, and AUC was calculated by connecting each plot with a straight line. Bars indicate mean and standard error. Comparison between groups was performed by Wilcoxon's rank sum test (significance level: p<0.05 (two-sided)). AUC, area under curve. ns, not significant. (b) Global Assessment of Stomach Tone: The subject's impression of the overall effect on stomach tone was scored from 1 (much better) to 7 (much worse) on dot plots as well as boxplots. indicated (median, 25th to 75th percentiles, whiskers showing minimum and maximum values). Group effect and time effect were tested by ordinal logistic regression analysis from the data after 6 weeks and 12 weeks after intake (significance level: p<0.05 (two-sided)). (c) Change in gastric emptying rate after ingestion of liquid diet (12 weeks after ingestion): Subjects were administered liquid diet mixed with 100 mg of ¹³ C-acetic acid ⁽ 200 mL/200 kcal), and exhaled breath was collected over time. Gastric emptying rate (%dose/hr) of C-acetic acid was investigated. The gastric emptying rate is shown as mean and standard error. Group effect and time effect were tested by repeated measures two-way ANOVA (**p<0.001 (two-sided); †p<0.10 (two-sided)). Changes in Tmax before intake, 6 weeks after intake, and 12 weeks after intake (per-protocol)　The changes in Tmax before intake, 6 weeks after intake, and 12 weeks after intake are shown for each of the Placebo group and LG21 group. Plots and boxplots are shown (whiskers showing median, 25th to 75th percentiles, minimum and maximum values). Within-group comparison, Friedman test († p<0.10 (two-sided)). ns, not significant. Appetite type of subjects (before intake) Using the data before intake of the ITT population (n=28), the subjects' appetite types were classified, and the appetite score and Tmax for each type were shown in the figure. Appetite type was classified as follows from the answers to the four questions about appetite shown in Fig. (a). [Anorexia type] Subjects who answered 0 (does not apply at all) to 2 (does not apply somewhat) to 2 or more questions. [Voracious appetite type] Those who answered 5 (agree) to 6 (strongly agree) to 2 or more questions. [Intermediate type] Subjects who do not correspond to either anorexia type or ravenous type. (a) Radar chart of score average values by appetite type (0: not applicable at all to 6: very applicable). (b) Dot plot and boxplot of Tmax by appetite type (median, 25th to 75th percentiles, whiskers showing minimum and maximum values). Comparison between groups: Kruskal-Wallis test (significance level: p<0.05 (two-tailed)). ns, not significant. ITT, intention to treat. Subject's gastrointestinal symptom type (before ingestion) Using the pre-ingestion data of the ITT population (n=28), three factors were extracted from the severity of 14 general gastrointestinal symptoms by factor analysis, and hierarchical CLS analysis ( Ward's method) classified the subjects into three CLS. Radar charts show the average scores of 14 symptoms for each CLS. Gastrointestinal symptom score: 0 (none) - 6 (very severe). ITT, intention to treat.CLS, cluster. Effect of continuous LG21 intake on a strictly defined population of subjects with mild to moderate delayed gastric emptying (excluding both the hyperappetizing type and the suspected panenteric dysmotility type) (a) ΔTmax-AUC within the intake period: For each subject, plot the origin, ΔTmax after 6 weeks and ΔTmax after 12 weeks on a graph where the X-axis is the elapsed intake period (week) and the Y-axis is ΔTmax (min), and connect each plot with a straight line to obtain the AUC. was calculated. Bars indicate mean and standard error. Comparison between groups was performed by Wilcoxon's rank sum test (*p<0.05 (two-tailed)). AUC, area under curve. (b) Global Assessment of Stomach Tone: The subject's impression of the overall effect on stomach tone was scored from 1 (much better) to 7 (much worse) on dot plots as well as boxplots. indicated (median, 25th to 75th percentiles, whiskers showing minimum and maximum values). Group and time effects were tested by ordinal logistic regression analysis from 6-week and 12-week post-ingestion data (†p<0.10 (two-tailed)). (c) Change in gastric emptying rate after ingestion of liquid diet (12 weeks after ingestion): Subjects were administered liquid diet mixed with 100 mg of ¹³ C-acetic acid ⁽ 200 mL/200 kcal), and exhaled breath was collected over time. Gastric emptying rate (%dose/hr) of C-acetic acid was investigated. The gastric emptying rate is shown as mean and standard error. Group effects, time effects and interactions were tested by repeated measures two-way ANOVA (** p<0.001 (two-tailed)). Continuous ingestion of the test food in a strictly defined population of subjects with mild to moderate delayed gastric emptying (excluding both the hyperappetizing type and the type with suspected panenteric dysmotility) was associated with changes in the rate of gastric emptying after taking a liquid diet. Changes in the gastric emptying rate after taking a liquid diet, measured by the ¹³ C-breath gastric emptying test performed before and 12 weeks after the intake of the food, are shown in the figure. The target population is (a) Placebo group, (b) LG21 group. The gastric emptying rate is shown as mean±standard error. Group effect (before and after intake), time effect and interaction were tested by repeated measures two-way ANOVA (**p<0.001 (two-sided), †p<0.10 (two-sided)). Sequence of the 16S rRNA gene of lactic acid bacteria contained in the composition of a particularly preferred embodiment.

The present invention will be described in detail below.
The present invention relates to compositions containing lactic acid bacteria. More specifically, the present invention relates to a composition containing lactic acid bacteria as an active ingredient for regulating gastric motility.

[Active ingredient]
The composition of the present invention contains, as an active ingredient, a lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more sequence identity with the base sequence of SEQ ID NO:1.

A preferred example of the lactic acid bacteria of the genus Lactobacillus contained in the composition of the present invention is a strain belonging to the genus Lactobacillus and having a 16S rRNA gene having 90% or more sequence identity with the base sequence of SEQ ID NO: 1, A strain belonging to the same species as Lactobacillus gasseri OLL2716.

Lactobacillus gasseri OLL2716 has been internationally deposited at the National Institute of Technology and Evaluation Patent Organism Depositary (IPOD, NITE) (Room 120, Kazusa Kamatari 2-5-8, Kisarazu City, Chiba Prefecture, Japan) based on the Budapest Treaty. (depositor: Meiji Co., Ltd., accession number: FERM BP-6999, original deposit: May 24, 1999, date of transfer to deposit under the Budapest Treaty: January 14, 2000). Recent reclassification of lactic acid bacteria (Zheng J, Wittouck S, Salvetti E, Franz CMAP, Harris HMB, Mattarelli P, O'Toole PW, Pot B, Vandamme P, Walter J, Watanabe K, Wuyts S, Felis GE, Ganzle MG, Lebeer S.: A taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. : 2782-2858), the deposited strain is classified as Lactobacillus paragasseri.

As the Lactobacillus lactic acid bacteria contained in the composition of the present invention, strains substantially equivalent to the above deposited strains can also be used. A substantially equivalent strain means, for example, any of the following.
- A strain belonging to the genus Lactobacillus, whose 16S rRNA gene sequence is 90% or more, preferably 95% or more, more preferably 98% or more, more preferably 98.5% of the sequence of SEQ ID NO: 1 a strain having a sequence identity of greater than or equal to or greater than 98.7%, more preferably greater than or equal to 99%, and even more preferably 100%;
• A strain that has the same mycological properties as the deposited strain.
In addition, those skilled in the art can refer to Stackebrandt E, Ebers J. Taxonomic parameters revisited: tarnished gold standards.

The mycological properties of the deposited strain are shown below.
Morphology: Bacillus, does not produce gas from glucose, GC content 36.4%, Gram-positive, catalase-negative, lactate optically active DL type, does not grow at 15°C, glucose, mannose, fructose, galactose, sucrose, cellobiose, Utilizes lactose, trehalose, starch, and dextrin to produce acid.

SEQ ID NO: 1 in the sequence listing shows the base sequence (also referred to as nucleotide sequence) of the 16S rRNA gene of Lactobacillus gasseri OLL2716 (FERM BP-6999). In the context of this invention, reference to sequence identity means the percentage of the number of matching bases shared between the sequences when the two sequences are optimally aligned, unless otherwise stated. Analysis of nucleotide sequence identity can be performed by algorithms or programs well known to those skilled in the art (eg, BLASTN, BLASTP, BLASTX, ClustalW). Parameters when using programs can be appropriately set by those skilled in the art, and default parameters of each program may be used. Specific techniques of these analysis methods are also well known to those skilled in the art. Commercially available gene information processing software may be used for identity calculations.

The above-mentioned substantially equivalent strain is preferably a strain whose ability to regulate the gastric motility function of subjects (for example, humans) is comparable to the above-mentioned deposited strain.

The lactic acid bacteria of the genus Lactobacillus contained in the composition of the present invention may be mutagenized, genetically modified, or modified from the deposited strain or a strain substantially equivalent thereto, as long as it has the same gastric motility regulation ability as the deposited strain. It may be a strain bred by selection of natural mutants or the like.

In the following, Lactobacillus gasseri OLL2716 (FERM BP-6999) may be referred to as LG21.

The lactic acid bacteria contained in the composition of the present invention may be contained as a lactic acid bacteria culture solution or may be contained as a lactic acid bacteria fermentation product. The lactic acid bacteria culture solution can be obtained by culturing (proliferating) lactic acid bacteria with known medium components, and may be in a freshly cultured (proliferated) state, mixed with a cryoprotectant or the like and frozen, or dried. A concentrate obtained by concentrating a culture solution by filtration, centrifugation, or membrane separation, a dried product of the concentrate, or a concentrate obtained by increasing the number of lactic acid bacteria per unit weight of the culture solution may be used. The fermented product of lactic acid bacteria includes the product itself fermented by lactic acid bacteria as well as its processed product. The lactic acid bacteria fermented product itself includes, for example, fermented milk (specifically, yogurt and the like). Treated products include, for example, crude purified products, concentrates obtained by concentrating fermented products by filtration, centrifugation, or membrane separation, dried products of concentrates, concentrates obtained by increasing the number of lactic acid bacteria per unit weight of culture solution, etc. is included.

The lactic acid bacteria contained in the composition of the present invention may be viable or dead. Live bacteria are preferred.

In addition to lactic acid bacteria belonging to the genus Lactobacillus, which are active ingredients, and having a 16S rRNA gene having a sequence identity of 90% or more with the nucleotide sequence of SEQ ID NO: 1, the composition of the present invention contains other lactic acid bacteria and yeasts. and bifidobacteria. Examples of other lactic acid bacteria include other lactic acid bacteria belonging to the genus Lactobacillus and lactic acid bacteria belonging to the genus Streptococcus. An example of the former is Lactobacillus delbrueckii (Delbrueckii) subspecies bulgaricus and an example of the latter is Streptococcus thermophilus.

[Use]
(Modulation of gastric motility, improvement of delayed gastric emptying, and inhibition of excessive gastric emptying rate)
The compositions of the present invention can be used for regulation of gastric motility. Gastric motility can be assessed by gastric motility parameters. As examples of gastric motility parameters, the time (Tmax) at which the gastric emptying rate reaches its peak after taking a liquid meal and the maximum value of the gastric emptying rate over time (maximum gastric emptying rate) in the ¹³ C gastric emptying test. is mentioned.

In the context of the present invention, adjustment of gastric motility function means that at least one of improvement of delayed gastric emptying and suppression of excessive gastric emptying rate is achieved, unless otherwise specified.

Delayed gastric emptying refers to the delay in the time it takes to empty the stomach contents into the duodenum. Tmax is an index for this. A delayed gastric emptying is defined as a Tmax greater than or equal to 55 minutes. In the context of the present invention, references to delayed gastric emptying include mild to moderate delayed gastric emptying (Tmax >55 min and <75 min), unless otherwise stated. The compositions of the present invention are suitable for ameliorating mild to moderate delayed gastric emptying and are particularly suitable for use when there is mild to moderate delayed gastric emptying and stomach upset may occur. Suitable for

Suppression of the excessive gastric emptying rate can be rephrased as a reduction in the emptying rate of gastric contents into the duodenum. Inhibiting gastric emptying rate (reducing the rate of gastric emptying into the duodenum) involves reducing the peak gastric emptying rate. The composition of the present invention has a maximum gastric emptying rate of 20% dose/hr or more, preferably 21% dose/hr or more, more preferably 21% dose/hr or more, and still more preferably 22% dose/hr or more. Suitable for use when Also, in such cases, it is particularly suitable for use in any one selected from the group consisting of treatment of stomach upset, treatment of stomach pain, treatment of nausea, and appetite enhancement.

When food is ingested, the fundus of the stomach actively relaxes and accepts the ingested food, which is then ground up by contraction of the antrum, and the porridge-like substance is discharged from the pylorus into the duodenum. In other words, the pyloric vestibule is the place where the ingested food becomes porridge, and the porridge stored in the pyloric vestibule is gradually expelled into the duodenum in conjunction with the opening and closing of the pylorus. Therefore, the delayed time to gastric emptying and abnormal gastric emptying rate are considered to independently constitute abnormal gastric emptying.

Also, in gastric emptying, the coordinated movement of the stomach and duodenum is important from the viewpoint of digestion and absorption. The duodenum contributes to the normal control of digestion and absorption through hormone secretion and the vagus nerve in order to control digestion and absorption so that postprandial blood glucose levels do not become excessive. A composition of the present invention capable of inhibiting the rate of gastric emptying (reducing the rate of gastric emptying into the duodenum) is suitable for improving the coordination of the stomach and duodenum. Therefore, the composition of the present invention can also be said to be a composition for improving the coordinated movement of the stomach and duodenum and a composition for adjusting the coordinated movement of the stomach and duodenum.

(Difference from conventional technology and application)
The applications of gastric motor function adjustment, improvement of delayed gastric emptying, and inhibition of excessive gastric emptying rate provided by the present invention are new and different from the prior art.

The relationship between gastric motility and the severity of symptoms of dyspepsia, which is chronic stomach discomfort, is not clear, but a recent meta-analysis reports that the relationship is small. Specifically, functional dyspepsia (FD) is generally classified into two subtypes, specifically, postprandial complaints syndrome related to meals and epigastralgia syndrome with discomfort around the pit of the stomach. Abnormal gastric motility is observed in a relatively large number of patients with postprandial distress syndrome (hereinafter referred to as PDS), which is mainly characterized by satiety, but it is said to account for half or less of the patients. In recent years, visceral hypersensitivity, which is thought to be caused by stress, etc., has become apparent, and it is believed that 30 to 40% of people, even with normal gastric motility, develop symptoms of dyspepsia due to hypersensitivity.

The following may be excluded from the uses of the composition of the present invention: suppression of gastrin production, prevention/improvement of functional gastrointestinal disorders, improvement of upper gastrointestinal flora, promotion of ghrelin secretion, improvement of gastric flora, Helicobacter pylori eradication-independent reduction of stomach bloating, reduction of abdominal bloating, improvement of subjective symptoms of gastroesophageal reflux disease that occurs independent of gastric acid secretion, reduction of bifidobacteria in the stomach, Increased Prevotella, increased ghrelin gene expression in stomach tissue, decreased gastric Bacteroidetes/Proteobacterial occupancy, increased gastric acidobacterial occupancy.

In addition, the following subjects may be excluded from the subjects to be ingested with the composition of the present invention: Helicobacter pylori infected persons, persons taking gastric acid secretion inhibitors, persons with Helicobacter pylori-negative functional gastrointestinal disorders, and functional dyspepsia patients. .

(others)
The compositions of the present invention can be used even when combined with other gastric or duodenal therapies. Such other therapies include drug therapy, surgery, other probiotics (eg, intake of other lactobacilli, bifidobacteria, etc.), intake of health foods and supplements, exercise therapy, and the like.

[Composition]
(Food composition, etc.)
The composition of the invention can be a food composition or a pharmaceutical composition. Foods and pharmaceuticals include those for humans as well as non-human animals, unless otherwise specified. Unless otherwise specified, foods include general foods, functional foods, nutritional compositions, and therapeutic foods (things that serve the purpose of treatment. A doctor gives a diet prescription and a dietitian etc. prepares a menu according to it). foods cooked according to the above), dietary therapy foods, ingredient-adjusted foods, nursing care foods, and therapeutic support foods. Foods include not only solids but also liquids such as beverages, drinks, liquid foods, and soups, unless otherwise specified. Functional foods refer to foods that can impart predetermined functionality to living organisms. Functional foods, special purpose foods, dietary supplements, health supplements, supplements (for example, tablets, coated tablets, sugar-coated tablets, capsules, liquids, etc.), beauty foods (for example, diet foods), etc. It includes general health foods. In the present invention, "functional food" includes health foods to which health claims based on food standards of Codex (FAO/WHO Joint Food Standards Committee) are applied.

(subject)
The compositions of the present invention are useful in subjects in need of modulation of gastric motility, subjects with delayed gastric emptying, more particularly subjects with mild to moderate delayed gastric emptying, especially those with mild to moderate gastric emptying. Suitable for ingestion/administration to subjects who are delayed and may experience stomach upset. In addition, the composition of the present invention is suitable for subjects who need suppression of gastric emptying rate, more specifically, the maximum gastric emptying rate is 20% dose/hr or more, preferably 21% dose/hr or more, more preferably 21% dose/hr or more. More than dose/hr, more preferably 22% dose/hr or more is suitable for subjects to take. Furthermore, subjects who need suppression of gastric emptying rate and who need any one selected from the group consisting of gastric disorder treatment, gastric pain treatment, nausea treatment, and appetite enhancement are ingested is particularly suitable for

The above subjects include infants, children, adults (15 years old and over), middle-aged and elderly people, elderly people (65 years old and over), people during and after illness, pregnant women, women in childbirth, men and women. In addition, the composition of the present invention is suitable for long-term ingestion because the active ingredient is lactic acid bacteria that have been eaten for a long time.

(Administration route)
The composition of the present invention may be administered parenterally, for example, through a tube (gastrostomy, enterostomy), nasally, or orally. Oral administration is preferred.

(Content and dose of active ingredient)
The content of lactic acid bacteria in the composition of the present invention may be an amount that exhibits the desired effect. The dosage or intake of the composition can be appropriately set in consideration of various factors such as the subject's age, weight, and symptoms. 10 ⁷ to 5×10 ¹⁰ pieces, preferably 5×10 ⁷ to 5×10 ¹⁰ pieces, more preferably 1×10 ⁸ to 5×10 ¹⁰ pieces, 5×10 It is more preferable to contain ⁸ to 5×10 ¹⁰ , more preferably 5×10 ⁸ to 2×10 ¹⁰ .

In addition, when 10 ⁷ or more lactic acid bacteria are contained per 1 g of the composition, the daily dose of the composition can be, for example, 0.5 g or more, 1 g or more, and 5 g or more. It can be 10 g or more, preferably 20 g or more, and more preferably 30 g or more. Regardless of the lower limit, the upper limit of the daily dose of the composition can be 500 g or less, preferably 400 g or less, more preferably 200 g or less, and 125 g or less. and more preferably 100 g or less.

The composition may be administered/taken once a day, or may be administered multiple times a day, for example, three times at each meal. The composition contains, as an active ingredient, lactobacillus, which has been widely used as food. Therefore, the composition of the present invention may be ingested repeatedly or over a long period of time. can be ingested.

(other ingredients, additives)
The composition of the present invention may contain other food or pharmaceutical acceptable active ingredients and nutritional ingredients. Examples of such ingredients include amino acids (e.g., lysine, arginine, glycine, alanine, glutamic acid, leucine, isoleucine, valine), carbohydrates (glucose, sucrose, fructose, maltose, trehalose, erythritol, maltitol, palatinose). , xylitol, dextrin), electrolytes (e.g. sodium, potassium, calcium, magnesium), vitamins (e.g. vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, biotin, folic acid, pantothenic acid and nicotinic acids), minerals (eg, copper, zinc, iron, cobalt, manganese), antibiotics, dietary fiber, proteins, lipids, and the like.

The composition may further contain food or pharmaceutical acceptable additives. Examples of such additives include inert carriers (solid and liquid carriers), excipients, surfactants, binders, disintegrants, lubricants, solubilizers, suspending agents, coating agents, coloring agents. agents, preservatives, buffers, pH adjusters, emulsifiers, stabilizers, sweeteners, antioxidants, flavors, acidulants, natural products. More specifically, water, other aqueous solvents, pharmaceutically acceptable organic solvents, collagen, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium alginate, water-soluble dextran, water-soluble dextrin, sodium carboxymethyl starch, Pectin, xanthan gum, gum arabic, casein, gelatin, agar, glycerin, propylene glycol, polyethylene glycol, petroleum jelly, paraffin, stearyl alcohol, stearic acid, human serum albumin, mannitol, sorbitol, lactose, sucralose, stevia, aspartame, acesulfame potassium, Citric acid, lactic acid, malic acid, tartaric acid, phosphoric acid, acetic acid, fruit juice, vegetable juice, and the like.

(dosage form/form)
The pharmaceutical composition of the present invention includes solid preparations such as tablets, granules, powders, pills and capsules, liquid preparations such as liquids, suspensions and syrups, gels, aerosols and the like, which are suitable for oral administration. can be any dosage form.

The food composition of the present invention may be prepared in any form such as solid, liquid, mixture, suspension, powder, granule, paste, jelly, gel, capsule and the like. Moreover, the food composition according to the present invention can be in any form such as dairy products, supplements, confectionery, beverages, drinkable preparations, seasonings, processed foods, side dishes, soups, and the like. More specifically, the composition of the present invention can be used in fermented milk, lactic acid beverages, lactic beverages, milk beverages, soft drinks, ice creams, tablets, cheeses, breads, biscuits, crackers, pizza crusts, prepared milk powders, and liquid diets. , foods for the sick, nutritional foods, frozen foods, processed foods, etc., and granules, powders, pastes, concentrated liquids, etc. for mixing with beverages and foods. can be done. Fermented milk refers to fermented milk and lactic acid beverages defined in the “Ministerial Ordinance Concerning Ingredient Standards for Milk and Dairy Products (hereinafter abbreviated as “Milk Ordinance”)”. Fermented milk in the Ministerial Ordinance for Milk, etc. refers to milk or milk containing non-fat milk solids equivalent to or higher than milk, fermented with lactic acid bacteria or yeast, and pasty or liquid, or frozen.

In one preferred embodiment of the food composition, 16S belonging to the genus Lactobacillus and having a predetermined sequence identity with the nucleotide sequence of SEQ ID NO: 1 is added to fermented milk produced by fermentation with one or more lactic acid bacteria. A lactic acid bacterium having an rRNA gene is added as an active ingredient.

(others)
In the production of the composition of the present invention, the step of adding lactic acid bacteria can be selected as appropriate. The stage of blending is not particularly limited as long as the characteristics of the lactic acid bacteria are not significantly impaired. For example, when the composition of the present invention is used as fermented milk, fermented milk can be produced by adding predetermined lactic acid bacteria as a starter to raw material milk, fermenting the mixture, and increasing the number of lactic acid bacteria. As a starter, it is preferably carried out with Lactobacillus delbrueckii (Delbrueckii) subspecies bulgaricus and Streptococcus thermophilus. According to the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO), fermented milk (yoghurt) is made from milk and lactic acid bacteria and contains Lactobacillus delbrueckii (Derbrueckii) subspecies bulgaricus and Streptococcus thermophilus. This is because it is defined as being produced from dairy products such as milk and powdered skim milk by lactic acid fermentation by both bacteria.

The composition of the present invention can be labeled with the purpose of use (application), and can be labeled with the recommendation that it should be taken by specific subjects. Labeling can be direct or indirect. Examples of direct labeling are the product itself, packages, containers, labels, tags, and other tangible items. Examples of indirect labeling are: Websites, storefronts, pamphlets, exhibitions, seminars such as media seminars, books, newspapers, magazines, television, radio, mail, e-mail, voice, etc., including advertising and publicity activities by place or means.

Purposes of use (applications) include "regulating gastric motility function", "improving delayed gastric emptying", "suppressing excessive gastric emptying rate", "maintaining good gastric motility", and "improving gastric motility". "prevents disturbance of gastric motility", "regulates the coordinated movement of the stomach and duodenum", and "reduces burden by properly discharging stomach contents into the duodenum". can.

The present invention provides a method for adjusting gastric motility, a method for reducing the rate of excretion of gastric contents into the duodenum, a treatment for gastric disorders, and a treatment for gastric pain, comprising the step of administering a given lactic acid bacterium. , treatment of nausea, and appetite enhancement, wherein such methods are provided after the step of administering an active ingredient to achieve a desired improvement in a subject. can include the step of checking that the Such examinations include stomach health questionnaires, gastroscopic examinations, and measurements of gastric emptying rate and its peak. The examination may be performed by the subject himself/herself, or may be performed by a person other than the subject.

The present invention will be described in more detail below using examples.

[Method]
(test design)
A double-blind, parallel-group, placebo-controlled, randomized controlled trial was conducted in which subjects were assigned to either the LG21 group or the placebo group. The study was conducted from December 2018 to April 2019 at the Tokyo Center Clinic (Tokyo, Japan). The study was approved by the Ethics Committee of Meiji Co., Ltd. and the National Council of Clinical Research (Tokyo, Japan) from the viewpoint of ethical and scientific validity. The ethical principles based on the Declaration of Helsinki and the ethical guidelines for epidemiological research were complied with, the purpose and contents of the study were fully explained to the subjects before participating in the study, and written informed consent was obtained from all subjects. .

(subject)
We recruited Japanese people aged 20-64 years who were untreated and in good health but who occasionally experienced stomach upset. During the screening (SCR) test, during the past month, you may have experienced mild (nearly unnoticeable) to moderately severe stomach upset (sometimes interfering with your daily life due to painful stomach upset). In addition, delayed gastric emptying was confirmed by the ¹³ C expiratory gastric emptying test, which showed that the time to peak gastric emptying (Tmax) after ingestion of a liquid diet was 55 min or longer. Those who met these selection criteria and did not meet any of the following exclusion criteria were selected as eligible cases. Severe delayed gastric emptying (Tmax ≥ 75 min) and severe heartburn or reflux symptoms during SCR. Persons who have visited a medical institution for diabetes or gastrointestinal disease in the last 6 months. Subjects suspected of having diabetes, gastrointestinal disease, and severe renal impairment based on blood tests (hematological and biochemical), medical interview, and physical examination during SCR. Subjects who have had painful stomach discomfort for more than 6 months and have been habitual for the past 3 months (suspected functional dyspepsia). Those who have a history of H.pylori positive determination or H.pylori eradication treatment by blood test at SCR. In addition, those who are judged to be inappropriate as subjects by the principal investigator.

(Standard value of Tmax in SCR)
Those with a Tmax of 55 min or more and less than 75 min were selected as subjects. This reference value corresponds to the average Tmax of Japanese healthy subjects +1SD or more and less than +3SD. Specific values are based on the survey report of the Japan Smooth Muscle Society (Tmax average value and SD are 45 min and 10 min, respectively) [Nakata, K., et al. "The present and the future in gastric emptying study assessed by 13C -
Acetate breath test-with special reference to the standardization of the method." J Smooth Muscle Res 6 (2002): J75-J91.] There is no international consensus on the reference value for gastroparesis, the pathologic condition of delayed gastric emptying. However, the need for a strict definition has been pointed out. For example, cases exceeding +3SD of the mean value for healthy adults have been proposed [Stanghellini, Vincenzo, and Jan Tack. "Gastroparesis: separate entity or just a part of dyspepsia ?." Gut 63.12 (2014): 1972-1978.][Keller, Jutta, et al. "Expert consensus document: Advances in the diagnosis and classification of gastric and intestinal motility disorders." Nature Reviews Gastroenterology & Hepatology 15.5 (2018) : 291.] In this study, +3SD or more was considered gastroparesis and excluded, while +1SD and less than +3SD were considered mild to moderate delayed gastric emptying and were included in the study.

(test protocol)
Allocators randomly assigned pooled subjects to two groups. Stratified allocation by sex and body type was performed. The placebo group ingested 85 g/piece of yogurt fermented with Lactobacillus delbrueckii subsp. The LG21 group ingested LG21-containing yogurt (LG21: 10 ⁹ CFU or more per piece) in which LG21 was added to the same yogurt. The nutritional component values per one piece (85g) of the placebo yogurt and the yogurt containing LG21 were 68kcal for energy, 2.9g for protein, 2.6g for fat, 8.3g for carbohydrate, 37mg for sodium, and 102mg for calcium. After confirming that they could not be identified by flavor, appearance, etc., the subjects were asked to take the assigned test food once a day (85g) for 12 weeks. Ingestion time was not limited.

[evaluation]
( ^13C breath gastric emptying test)
A ¹³ C breath test method gastric emptying test using a liquid diet was performed before ingestion of the test food, 6 weeks after ingestion, and 12 weeks after ingestion. 100 mg of ¹³ C-acetic acid (− ¹³ COOH; Na salt) labeled with ¹³ C (atomic weight 13), a stable isotope, was mixed with 200 mL/200 kcal of liquid food (Ensure Liquid: Abbott). Exhaled breath was collected several times over time from 5 minutes before to 90 minutes after taking the liquid food, and the abundance ratio of ¹³ CO ₂ in breath was measured with an infrared spectrophotometer (POCone (registered trademark), Otsuka, Japan). Using the exhaled ¹³ _CO2 abundance ratio before taking the liquid diet as a baseline, the amount of change (Δ‰) in the exhaled ¹³ _CO2 abundance ratio of the exhaled breath sampled after taking the liquid diet was measured, and the amount of _CO2 produced in the body per hour was calculated as the body surface area. The rate of gastric emptying into the duodenum (%dose/hr) was calculated by approximating with ×300 [Braden, Barbara, et al. "The [13C] acetate breath test accurately reflects gastric emptying of liquids in both liquid and semisolid test meals." Gastroenterology 108.4 (1995): 1048-1055.]. The peak time (Tmax) in the gastric emptying rate over time was used as an indicator of gastric emptying ability. Liquid diet was taken at 10:30 am on both examination days. Subjects were fasted from 9:00 pm the day before the test to the end of the test on the day, but they were allowed to drink water until 8:00 am on the day of the test. 13C-acetic acid excreted from the stomach together with liquid food is rapidly excreted as ^13CO ₂ through the duodenum and metabolism in the liver. Although it is a multi-step test, it has been reported that the use of liquid food correlates well with direct scintigraphic results [Goetze, O., et al. "Effects of postgastric 13C -acetate processing on measurement of gastric emptying: a systematic investigation in health." Neurogastroenterology & Motility 21.10 (2009): 1047-e85.] [Futagami, S, et al. "Nizatidine improves clinical symptoms and gastric emptying in patients with functional dyspepsia "Digestion, 86(2), 114-121. (2012).].

(Subject's comprehensive evaluation of stomach condition)
After 6 and 12 weeks of ingestion of the test food, a questionnaire survey was conducted on the subject's impression of the overall effect on gastric symptoms. In response to the question, "How have your gastric symptoms been in the last week compared to the baseline period before you started taking the test food?" -controlled trial of acotiamide for meal-related symptoms of functional dyspepsia." Gut 61.6 (2012): 821-828.]. 1 much better, 2 better, 3 slightly better, 4 no change, 5 slightly worse, 6 worse, 7 much worse.

(end point)
As the primary endpoint, intergroup comparison of ΔTmax-area under the curve (AUC) within the ingestion period (indicator of changes in gastric emptying capacity within the ingestion period) was performed. ΔTmax-AUC within the intake period for each subject was plotted on a graph with the elapsed intake period (week) on the X axis and ΔTmax (min) on the Y axis. , AUC was calculated by connecting each plot with a straight line.

As a secondary endpoint, we conducted a comprehensive evaluation of the subject's stomach condition after ingestion. In addition, 3 endpoints (change in Tmax before, 6 weeks and 12 weeks after intake in each group, odds ratio of delayed gastric emptying improvement in LG21 group to placebo group after 12 weeks of intake, 12 weeks after intake The change in gastric emptying rate after taking a liquid diet) was evaluated during the gastric emptying test.

(Statistical analysis)
Between-group comparisons at baseline were performed using Fisher's exact test for categorical variables and unpaired Student's t-test or Wilcoxon's rank sum test for continuous variables. Statistical analysis of the primary endpoint was performed using the Mann-Whitney U test. Statistical analysis of the impression score of overall effect on gastric tone after 12 weeks of ingestion was performed by ordinal logistic regression analysis. Changes in Tmax before, 6 weeks and 12 weeks after intake in each group, odds ratio of improvement in delayed gastric emptying in the LG21 group to the placebo group after 12 weeks of intake, flow during gastric emptying test after 12 weeks of intake Statistical analysis of changes in Tmax before and after ingestion of changes in gastric emptying rate after ingestion was conducted by the Friedman test. Odds ratio of improvement in delayed gastric emptying in the LG21 group to the placebo group was analyzed by logistic regression analysis. Gastric emptying test after 12 weeks of ingestion. The changes in gastric emptying rate over time were statistically analyzed using repeated measures two-way analysis of variance. The significance level was 5% on both sides. Efficacy evaluation was conducted in the per-protocol population (PP population) according to the study implementation plan prepared in advance.

[result]
Analysis result 1: PP analysis (PP population)
Subject Selection and Background Information We recruited 298 Japanese subjects (149 males and 149 females) aged 20-64 years who had stomach upset but were not receiving treatment. . A total of 28 subjects (4 males and 24 females) were ultimately determined to meet the inclusion criteria, and the 28 subjects were randomized (14 subjects in each group) and all completed the study. did. However, 27 people were included in the PP population (14 in the placebo group, 13 in the LG21 group) because one of the study completers was found to have violated the inclusion criteria.

As shown in the table below, there were no statistically significant inter-group differences in subject background data (baseline) in the intention to treat (ITT) group (4 males/23 females, mean age 41.1 ± 11.0 years). .

(primary endpoint)
The mean ± standard deviation of ΔTmax-AUC within the intake period was -7.5 ± 106.4 in the placebo group and -25.4 ± 55.9 in the LG21 group. Rejected (p<0.05). A non-parametric test was used to compare the ΔTmax-AUC within the intake period between groups, and no statistically significant difference was observed (Fig. 1(a)).

(secondary endpoint)
Subject's Global Assessment of Stomach Tone There was no statistically significant difference between the groups in the score of the subject's impression of the global effect of stomach tone (FIG. 1(b)).

(Changes in Tmax before ingestion, 6 weeks after ingestion, and 12 weeks after ingestion)
Regarding changes in Tmax before intake, 6 weeks after intake, and 12 weeks after intake, Tmax tended to decrease before and after intake, although not significantly, only in the LG21 group (p<0.10; Fig. 2).

(Odds ratio for improvement in delayed gastric emptying after 12 weeks of ingestion)
Subjects who showed improvement in delay of gastric emptying in subjects whose difference from the Japanese average Tmax (45 min) decreased by 30% or more before and after ingestion of the test food, the number of subjects with and without improvement was 12 w of ingestion of the test food. Later there were 5 and 9 in the placebo group and 9 and 4 in the LG21 group. The odds ratio of improvement in delayed gastric emptying in the LG21 group to the placebo group 12 w after ingestion was 4.1 (95% confidence interval: 0.8-20.2), which was not significant but showed a statistical trend (p<0.10).

(Transition of gastric emptying rate after taking liquid food after 12 weeks of ingestion)
During the gastric emptying test after 12 weeks of ingestion, the LG21 group tended to show a more restrained transition than the placebo group until 90 minutes after the end of the measurement (group effect p<0.10; (c) in Fig. 1).

(Discussion)
We investigated the effect of continuous LG21 intake on gastric motility in subjects with mild to moderate delayed gastric emptying by breath test. Analysis of the PP population showed no statistically significant inter-group differences in ΔTmax-AUC (primary endpoint) during the intake period, which is an index of changes in gastric emptying capacity during the intake period. However, compared to the LG21 group, the placebo group had a larger variance, and the homogeneity of variance was significantly rejected. was done. On the other hand, in the LG21 group, Tmax tended to decrease before and after ingestion, though not significantly (p<0.10). In addition, when patients who improved delayed gastric emptying by 30% or more were considered to have improved, the odds ratio of improved delayed gastric emptying in the LG21 group to the placebo group after 12 weeks of ingestion was 4.1 (95% confidence interval: 0.8-20.2), which was not significant. No, but statistically trended (p<0.10). These results suggest that continuous intake of LG21 may improve delayed gastric emptying.

Interestingly, the gastric emptying rate after taking a liquid diet 12 weeks after intake tended to be suppressed in the LG21 group compared to the placebo group until 90 minutes after the end of the measurement (p<0.10). ). Therefore, it was considered that continuous intake of LG21 not only improved delayed gastric emptying but also reduced the risk of rapid gastric emptying by suppressing the rate of emptying into the duodenum.

Analysis result 2: Analysis of strictly defined populations (type classification) of persons with mild and moderate delayed gastric emptying
In addition, subjects in this study were typed based on exploratory gastric symptoms. First, when focusing on the appetite type of the subjects, they were classified into three types: anorexia type (43%), intermediate type (36%), and strong appetite type (21%), as shown in Fig. 3(a). The ravenous type not only did not feel anorexia, but also had a low Tmax value, and it was judged that there was no problem with gastric emptying (Fig. 3(b)).

Next, we focused on the subject's digestive symptom type. For example, panenteric dysmotylity, including delayed gastric emptying, is known to occur in gastrointestinal motility disorders such as chronic intestinal pseudo-obstruction (CIPO). [Keller, Jutta, et al. "Expert Consensus Document: Advances in the Diagnosis and Classification of Gastric and Intestinal Motility Disorders." Nature Reviews Gastroenterology & Hepatology 15.5 (2018): 291.],[Mann, S. D., H S. Debinski, and M. A. Kamm. "Clinical characteristics of chronic idiopathic intestinal pseudo-obstruction in adults." Gut 41.5 (1997): 675-681.],[Cogliandro, Rosanna F., et al. "Is gastroparesis a gastric disease?." Neurogastroenterology & Motility 31.5 (2019): e13562.]. Therefore, in gastroparesis, it has been proposed that upper gastrointestinal symptoms should be restricted to abnormalities associated with delayed gastric emptying [Camilleri, Michael, et al. "Gastroparesis." Nature Reviews Disease Primers 4.1 (2018): 1-19.]. As shown in Fig. 4, the digestive symptom types of the subjects were PDS-like alone or with vague stomach upset (CLS1: 51.9%), PDS-like accompanied by EPS-like or lower abdominal symptoms (CLS2). : 22.2%) and PDS-like accompanied by gastrointestinal bloating and heartburn (CLS3: 25.9%). The third type was strongly suspected of panenteric dysmotility, and should be distinguished.

(primary endpoint, secondary endpoint)
Therefore, when we analyzed the subject population (rigorously defined population with mild and moderate delayed gastric emptying), excluding both type of appetite and suspected panentericdysmotility, the primary endpoint was A significant inter-group difference was observed in ΔTmax-AUC within the ingestion period (p<0.05; FIG. 5(a)). In addition, there was a non-significant improvement trend in the LG21 group compared to the placebo group in the impression score of the general effect on stomach condition (p<0.10; FIG. 5(b)).

(Transition of gastric emptying rate after taking liquid food after 12 weeks of ingestion)
Furthermore, during the gastric emptying test 12 weeks after ingestion, changes in the gastric emptying rate over time after taking the liquid diet showed a change in the pattern of the interaction (interaction p <0.155; Fig. 5(c)). A comparison of before and after continuous intake of LG21 showed a statistical trend of an interaction, though not significant, suggesting a decrease in Tmax and a decrease in gastric emptying rate (p<0.10; Figure 1). 6).

As described above, by rigorously defining subjects with mild to moderate delayed gastric emptying, excluding both those with a strong appetite and those with suspected panenteric dysmotility, it was possible to determine the effect of continuous intake of LG21 on improving gastric emptying. I was able to confirm. In addition, subjective symptoms tended to improve the impression of the overall effect of gastric condition, suggesting that controlling not only gastric emptying ability but also the rate of emptying into the duodenum is equally important for normal gastric motility. suggested to be important.

(Correlation between maximum gastric emptying rate and subjective symptoms related to stomach)
Using pre-ingestion data, we investigated the correlation between two gastric motility parameters, Tmax and the maximum gastric emptying rate over time (hereinafter referred to as the maximum gastric emptying rate), and the degree of subjective symptoms related to the stomach. Examined. As shown in the table below, belching was associated with Tmax (r=0.53:p<0.05) in a strictly defined population of subjects with mild to moderate delayed gastric emptying. However, the highest gastric emptying rate and gastric upset (r=0.56:p<0.05), gastric pain (r=0.54:p<0.05), nausea (r=0.52:p<0.05), and diet A correlation was observed between the feeling of being hungry (r=-0.77:p<0.01) and the feeling of having an appetite in the morning (r=-0.62:p<0.05).

Therefore, we found that excessive gastric emptying rate (mainly, the maximum gastric emptying rate is too high), rather than delayed gastric emptying, may affect the severity of subjective symptoms.

sequence listing free text
SEQ ID NO:1 16s rRNA gene

Claims

A composition for regulating gastric motor function, containing a lactic acid bacterium belonging to the genus Lactobacillus and having a 16S rRNA gene having 98% or more sequence identity with the base sequence of SEQ ID NO: 1.
The composition according to claim 1, wherein the gastric motility modulation is at least one of improving delayed gastric emptying and inhibiting excessive gastric emptying rate.
The composition according to claim 1 or claim 2, wherein the lactic acid bacterium belongs to the same species as Lactobacillus gasseri OLL2716 (FERM BP-6999).
The composition according to any one of claims 1 to 3, wherein the lactic acid bacterium is Lactobacillus gasseri OLL2716 (FERM BP-6999).
5. The composition according to any one of claims 1 to 4, for ingesting 1.0×10 9 CFU or more of lactic acid bacteria per day.
The composition according to any one of claims 1 to 5, for ingesting 2×10 7 CFU or more of lactic acid bacteria per dose.
The composition according to any one of claims 1 to 6, which is fermented milk.
The composition according to any one of claims 1 to 7, comprising Lactobacillus delbrueckii subspecies bulgaricus and Streptococcus thermophilus.
The composition according to any one of claims 1 to 8, which is to be taken continuously for 4 weeks or longer.
The composition according to any one of claims 1 to 9, which is to be ingested by a person who has mild to moderate gastric emptying delay and may feel stomach upset.
The composition according to any one of claims 1 to 9, which is to be ingested by a person whose maximum gastric emptying rate is 20% dose/hr or more.
A composition for reducing the rate of excretion of gastric contents into the duodenum, containing lactic acid bacteria belonging to the genus Lactobacillus and having a 16S rRNA gene having 98% or more sequence identity with the nucleotide sequence of SEQ ID NO: 1.
The composition according to claim 12, which is for any one selected from the group consisting of treatment of stomach upset, treatment of stomach pain, treatment of nausea, and appetite enhancement.
A method for any selected from the group consisting of treating gastric upset, treating gastric pain, treating nausea, and increasing appetite by reducing peak gastric emptying rate.