Lactobacillus paracasei and tagatose composition for synergistic treatment of functional constipation

Abstract

The present invention relates to the fields of microbiology and food biotechnology, and provides a composition of Lactobacillus paracasei and tagatose for synergistically treating functional constipation. The active ingredients of the composition are Lactobacillus paracasei ZYhyy-004 and tagatose. The Lactobacillus paracasei is named ZYhyy-004, and this strain is deposited in the China General Microbiological Culture Collection Center, and the taxonomic name is Lacticaseibacillus paracasei , and the deposit number is CGMCC No. 31554, and the deposit date is August 5, 2024. Experiments have confirmed that in the composition of Lactobacillus paracasei and tagatose described in the present application, Lactobacillus paracasei ZYhyy-004 and tagatose have a synergistic effect in treating and / or improving the functional constipation of animals, and can be used to improve or treat functional constipation.

Description

Technical Field

[0001] The present invention belongs to the fields of microbiology and food biotechnology, and particularly relates to a combination of Lactobacillus paracasei and tagatose for synergistically treating functional constipation. Background Art

[0002] Under the shroud of the modern fast-paced lifestyle, constipation has become a common problem affecting public health. The urbanization process has led to a significant reduction in people's daily physical activity. The excessive intake of high-fat, high-oil, and finely processed foods, combined with the decline of physical functions due to aging, has caused the incidence of constipation to rise year by year. Globally, people of different regions and ages are deeply troubled by it. Among the young and middle-aged groups, due to work pressure and bad work and rest habits, the prevalence of chronic constipation can reach about 15%. In the elderly population, affected by factors such as slowed intestinal peristalsis, this proportion is even as high as 30% or more. Constipation not only causes obvious discomfort such as difficult defecation and abdominal distension, but also interferes with the normal absorption and excretion functions of the intestine in the long term, destroys the intestinal mucosal barrier, and is closely related to the increased risks of serious diseases such as intestinal inflammation and colorectal cancer, which promotes the scientific research and medical communities to accelerate the exploration of effective prevention and treatment strategies.

[0003] The key role of probiotics in maintaining intestinal health has become increasingly prominent. As beneficial microorganisms that can coexist harmoniously with the human body, they reshape the intestinal flora homeostasis and strengthen the intestinal immune defense by competitively inhibiting the adhesion of harmful bacteria to the intestinal mucosa and metabolizing antibacterial substances. At the same time, tagatose, as a new type of functional oligosaccharide, is coming into the public eye. It has the characteristics of low calorie and low blood sugar response, is difficult to be decomposed by digestive enzymes in the human intestine, but can be selectively utilized by beneficial bacteria such as Bifidobacterium, becoming the "exclusive energy source" for the proliferation of beneficial bacteria and stimulating the expansion of beneficial flora. However, there is a lack of relevant research on the combined use of probiotics and tagatose in existing studies. Summary of the Invention

[0004] Aiming at the problems existing in the prior art, the purpose of the present invention is to screen out Lactobacillus paracasei and a tagatose composition that can be used in combination with tagatose to provide a combination for synergistically treating functional constipation. The combined use of probiotics and tagatose can not only improve intestinal motility through the direct regulatory effect of probiotics, but also create excellent living and reproducing conditions for probiotics by using tagatose. By combining these two methods, a new path with both pertinence and sustainability for constipation treatment is created, which has great potential in the fields of functional foods, nutritional supplements and even clinical adjuvant treatment.

[0005] Lactobacillus paracasei stands out in the "tough journey" of the intestinal tract due to its excellent acid and bile tolerance. It can successfully reach the intestine, firmly adhere and colonize, continuously secrete active substances such as bacteriocins and lactic acid, regulate the intestinal pH value, inhibit the growth of harmful bacteria, and interact with intestinal epithelial cells to activate the neuroendocrine network in the intestine, facilitating regular intestinal peristalsis. Combining with the known properties of tagatose, the inventors conducted research, hoping to find Lactobacillus paracasei strains that can achieve synergistic effects in promoting intestinal health when used in combination with tagatose. The Lactobacillus paracasei strains screened in the early stage of the research include: Lactobacillus paracasei ZYhyy-004, Lactobacillus casei strain Shirota (LcS). However, the experimental results showed that when the above two strains of Lactobacillus paracasei were intervened alone, the constipation symptoms could be improved, but when Lactobacillus casei strain Shirota (LcS) was used in combination with tagatose, it had an inhibitory effect on the intervened constipated mice; when Lactobacillus paracasei ZYhyy-004 was used in combination with tagatose, it showed a promoting effect. In view of this, the inventors provided the following solutions of the present invention.

[0006] To achieve the above object, in the first aspect of the present invention, a strain of Lactobacillus paracasei capable of preventing and treating functional constipation, named ZYhyy-004, is provided. This strain is preserved in the General Microbiological Center of the China Committee for Culture Collection of Microorganisms, and the taxonomic name is Lacticaseibacillus paracasei , and the preservation number is CGMCC No. 31554, and the preservation date is August 5, 2024.

[0007] In the second aspect of the present invention, a composition of Lactobacillus paracasei and tagatose for synergistically treating functional constipation is provided. Among them, the active ingredients of the composition are Lactobacillus paracasei and tagatose;

[0008] The Lactobacillus paracasei is named ZYhyy-004. This strain is preserved in the General Microbiological Center of the China Committee for Culture Collection of Microorganisms, and the taxonomic name is Lacticaseibacillus paracasei , and the preservation number is CGMCC No. 31554, and the preservation date is August 5, 2024.

[0009] Further, in the composition, the final treatment dose of Lactobacillus paracasei named ZYhyy-004 is not less than 1.0 - 3.0×10 7 CFU / d / kg body weight.

[0010] Further, in the composition, the final treatment dose of tagatose is 0.167 - 2.5 g / d / kg body weight.

[0011] Further, the dosage form of the composition includes freeze-dried powder, capsule, tablet or granule.

[0012] The third aspect of the present invention provides the application of the Lactobacillus paracasei described in the first aspect above, or the composition described in the second aspect, in the preparation of a product for treating and / or improving functional constipation.

[0013] Furthermore, the product is a medicine.

[0014] Furthermore, the medicine is one or more of the following:

[0015] (1) The medicine can reduce the defecation time;

[0016] (2) The medicine can increase the number of fecal particles;

[0017] (3) The medicine can increase the water content of feces;

[0018] (4) The medicine can increase the small intestine propulsion rate.

[0019] The fourth aspect of the present invention provides a probiotic composition, which contains the Lactobacillus paracasei described in the first aspect, or the Lactobacillus paracasei and tagatose composition that can synergistically treat functional constipation described in the second aspect.

[0020] Furthermore, the probiotic composition also includes a medically acceptable carrier.

[0021] Strain preservation information:

[0022] The Lactobacillus paracasei is named ZYhyy-004. This strain is preserved in the China General Microbiological Culture Collection Center (CGMCC), address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; the classification name is Lacticaseibacillus paracasei , and the preservation number is CGMCC No. 31554, and the preservation date is August 5, 2024.

[0023] The beneficial effects of the present invention compared with the prior art are as follows:

[0024] 1. A probiotic strain capable of preventing and treating functional constipation is screened in this application. This strain is identified as Lactobacillus paracasei, with the preservation number CGMCC No. 31554 and the classification name Lacticaseibacillus paracasei .

[0025] 2. The Lactobacillus paracasei ZYhyy-004 described in this application can effectively increase the number of fecal particles and the water content of feces, reduce the defecation time, and increase the small intestine propulsion rate, thereby achieving the treatment of functional constipation. Its effect is significantly better than the commercially available Lactobacillus paracasei strain Shirota (LcS).

[0026] 3. It is first discovered in this application that the combined use of tagatose and Lactobacillus paracasei ZYhyy-004 has a better intervention effect on improving constipation in mice than the single intervention effect of Lactobacillus paracasei ZYhyy-004 or tagatose alone. The combination of the two shows a synergistic and promoting effect and reaches the level of drug intervention. Specifically, on the one hand, tagatose provides sufficient carbon sources for Lactobacillus paracasei, ensuring its strong metabolic activity and increasing its survival number in the intestine. On the other hand, the two work together to comprehensively tackle the problem of constipation from multiple dimensions such as optimizing the intestinal microbial community structure, improving the intestinal biochemical environment, and regulating intestinal nerve conduction. It is expected to fill the gap in existing constipation treatment methods with the advantages of being natural, safe, and efficient, and become a cutting-edge combination for future intestinal health management to serve the large group troubled by constipation. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The present invention will be further described below in conjunction with the drawings and embodiments:

[0028] Figure 1 Showing the successful results of modeling functional constipation mice; among them, A is the time of the first red stool, B is the number of feces in 2 hours, and C is the fecal water content;

[0029] Figure 2 Showing the results of treating functional constipation mice with different doses of Lactobacillus paracasei ZYhyy-004 and different doses of tagatose; among them, A is the time of the first red stool, B is the number of feces in 2 hours, and C is the fecal water content;

[0030] Figure 3 Showing the results of treating functional constipation mice after the combination of Lactobacillus paracasei ZYhyy-004 and tagatose at 1 - 3×10 8 CFU / d / kg and 2.5 g / d / kg; among them, A is the time of the first red stool, B is the number of feces in 2 hours, C is the fecal water content, and D is the intestinal propulsion rate;

[0031] Figure 4 Showing the synergistic effect (combined normalized equivalent hologram) after the combination of Lactobacillus paracasei and tagatose at 1 - 3×10 8 CFU / d / kg and 2.5 g / d / kg; among them, A is Lactobacillus paracasei ZYhyy-004, and B is Lactobacillus casei strain Shirota (LcS). DETAILED DESCRIPTION OF THE EMBODIMENTS

[0032] The implementation of the present invention is not limited to the following embodiments. Any formal modification and / or change made to the present invention will fall within the protection scope of the present invention. In the present invention, unless otherwise specified, all devices and raw materials can be purchased from the market or are commonly used in this industry. Without special indication, the methods used in the embodiments are general techniques in the art.

[0033] For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered specifically disclosed herein.

[0034] In the following examples, Lactobacillus paracasei ZYhyy-004 is derived from Zhongyuan Food Laboratory; tagatose is from Henan Yihengyuan Biotechnology Co., Ltd. Other chemical reagents used are purchased from regular chemical reagent suppliers.

[0035] In the following examples, the culture medium formulations involved include:

[0036] MRS liquid medium, and its formulation is: 10 g / L peptone, 5 g / L beef powder, 4 g / L yeast powder, 2 g / L glucose, 1 ml / L Tween 80, 2 g / L dipotassium hydrogen phosphate, 5 g / L sodium acetate, 2 g / L ammonium citrate, 0.2 g / L magnesium sulfate, 0.05 g / L manganese sulfate, distilled water.

[0037] Example 1: Microbial culture and tagatose preparation

[0038] 1) Preparation of Lactobacillus paracasei ZYhyy-004 cell bodies:

[0039] An isolated probiotic bacterium was identified as Lactobacillus paracasei Lacticaseibacillus paracasei , and it was deposited in the China General Microbiological Culture Collection Center (CGMCC), with the deposit number CGMCC No. 31554 and the deposit date August 5, 2024.

[0040] After the isolated Lactobacillus paracasei ZYhyy-004 was passaged twice in MRS liquid medium, it was inoculated into MRS liquid medium at an inoculation amount of 2%, and cultured at 37 ± 1 °C for 12 h. The supernatant was removed by centrifugation (4000 rpm, 10 min), and after washing the cell bodies twice with PBS, when used for gavage, it was resuspended with 0.9% physiological saline and the concentration of its cell suspension was adjusted to 1.0 - 3.0×10 9 CFU / g.

[0041] 2) Preparation of Lactobacillus casei strain Shirota (LcS) cell bodies:

[0042] After Lactobacillus paracasei Shirota strain (LcS) was subcultured twice in MRS liquid medium, it was inoculated in a modified MRS liquid medium at a 2% inoculum and cultured at 37±1℃ for 12h. The supernatant was removed by centrifugation (4000 rpm, 10 min), and the bacteria were washed twice with PBS. When gavage was performed, the bacteria were resuspended in 0.9% saline and the concentration of the bacterial suspension was adjusted to 1.0-3.0×10 9 CFU / g.

[0043] 3) Preparation of tagatose intragastric solution:

[0044] When administered intragastrically, the drug was resuspended in 0.9% saline and the concentrations were adjusted to 0.034 g / mL, 0.167 g / mL, and 0.5 g / mL.

[0045] Example 2: Animal Experiment

[0046] In order to explore whether Lactobacillus paracasei ZYhyy-004, Lactobacillus paracasei Shirota strain (LcS), tagatose and Lactobacillus paracasei-tagatose composition have therapeutic and / or improving effects on functional constipation, the following animal experiment was conducted in this example, and the specific steps are as follows:

[0047] The experimental animals used were SPF-grade BALB / c (6-week-old, female) mice purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0048] The animal experiment was divided into 12 groups, namely blank group, model group, drug group, high-dose tagatose group, medium-dose tagatose group, low-dose tagatose group, low-dose Lactobacillus paracasei ZYhyy-004 group, medium-dose Lactobacillus paracasei ZYhyy-004 group, high-dose Lactobacillus paracasei ZYhyy-004 group, Lactobacillus paracasei Shirota strain (LcS) group, Lactobacillus paracasei ZYhyy-004 + medium-dose tagatose mixed group, and Lactobacillus paracasei Shirota strain (LcS) + medium-dose tagatose mixed group, with 8 mice in each group, for a total of 96 mice.

[0049] The mice were kept under the following conditions: temperature 24°C, 12h light, 12h dark, and bedding was changed every three days. After one week of adaptive feeding, each mouse was gavaged with 15 mg / kg bw of loperamide hydrochloride every day, and weighed once a week.

[0050] The blank group was gavaged with 0.9% saline until the end of the experiment;

[0051] Model group and each intervention group: First, gavaged with 0.1 mL of loperamide hydrochloride at a dose of 15 mg / kg b.w. until the model was successfully established (7 - 14 days). After the successful establishment of the model, the model group and the intervention groups were gavaged with 0.1 mL of loperamide hydrochloride at a dose of 15 mg / kg b.w. every other day until the end of the experiment; at the same time, the drug group was gavaged with polyethylene glycol 4000 powder.

[0052] Each intervention group (the gavage volume was 0.1 mL, and the gavage lasted for 2 - 3 weeks):

[0053] High-dose tagatose group, medium-dose tagatose group, low-dose tagatose group: Respectively gavaged with low, medium, and high doses of tagatose (low dose 0.167 g / d / kg, medium dose 0.833 g / d / kg, high dose 2.5 g / d / kg);

[0054] Low-dose Lactobacillus paracasei ZYhyy - 004 group, medium-dose Lactobacillus paracasei ZYhyy - 004 group, high-dose Lactobacillus paracasei ZYhyy - 004 group: Respectively gavaged with low, medium, and high doses of Lactobacillus paracasei ZYhyy - 004 (low dose 1 - 3×10 7 CFU / d / kg, medium dose 1 - 3×10 8 CFU / d / kg, high dose 1 - 3×10 9 CFU / d / kg);

[0055] Lactobacillus casei strain Shirota (LcS) group: Gavaged with Lactobacillus casei strain Shirota (LcS) at a dose of 1 - 3×10 8 CFU / d / kg;

[0056] Lactobacillus paracasei ZYhyy - 004 + medium-dose tagatose mixed group: Simultaneously gavaged with Lactobacillus paracasei ZYhyy - 004 at a dose of 1 - 3×10 8 CFU / d / kg and tagatose (0.833 g / d / kg);

[0057] Lactobacillus casei strain Shirota (LcS) + medium-dose tagatose mixed group: Simultaneously gavaged with Lactobacillus casei strain Shirota (LcS) at a dose of 1 - 3×10 8 CFU / d / kg and tagatose (0.833 g / d / kg).

[0058] Example 3: Detection of fecal water content, number of defecations within 2 hours, and time of the first red defecation

[0059] In this example, the fecal water content, number of defecations within 2 hours, and time of the first red defecation in each group of the animal experiment in Example 2 were measured. The specific methods and results are as follows:

[0060] Determination of fecal water content: On the 29th day, after the gavage was completed, each mouse was placed individually in a cage box lined with absorbent paper to collect feces. The weight of the collected feces was the wet weight. After freeze-drying, it was the dry weight. The fecal water content was calculated according to formula (1):

[0061] Fecal water content / % = (fecal wet weight - fecal dry weight) / fecal wet weight × 100% (1)

[0062] Number of feces excreted within 2 hours: On the 30th day, the blank group was given 0.1 mL of 0.9% normal saline, and the model group and the intervention groups were all given 0.1 mL of loperamide hydrochloride solution (15 mg / kg b.w). After 1 h, each mouse was placed individually in a cage box lined with absorbent paper, and feces were collected every 30 minutes for a total of 2 hours.

[0063] Time for the first red feces excretion: On the 30th day, the blank group was given 0.1 mL of 0.9% normal saline, and the model group and the intervention groups were all given 0.1 mL of loperamide hydrochloride solution (15 mg / kg b.w). After 1 h, 0.1 mL of 0.6% (m:v) carmine was gavaged to each group. Starting from the gavage of carmine, the time for each mouse to excrete the first red feces was recorded.

[0064] As Figure 1 shown in the results, 7 days after modeling, the time for the first red feces excretion, the number of feces, and the fecal water content of the mice in the model group were 4.3 times, 3.5 times, and 1.76 times that of the blank group, respectively, and there were significant differences, indicating that the constipation model was successfully established.

[0065] Compared with the model group, the performance of the intervention groups was as Figure 2 shown in the results. After 14 days of intervention with different doses of tagatose, the low dose of tagatose (0.167 g / d / kg), the medium dose of tagatose (0.833 g / d / kg), the high dose of tagatose (2.5 g / d / kg), the low dose of Lactobacillus paracasei ZYhyy - 004 (1 - 3×10 7 CFU / d / kg), the medium dose of Lactobacillus paracasei ZYhyy - 004 (1 - 3×10 8 CFU / d / kg), and the high dose of Lactobacillus paracasei ZYhyy - 004 (1 - 3×10 9 CFU / d / kg) all improved in the time for the first red feces excretion, the number of feces, and the fecal water content. Compared with the model group, the time for the first red feces excretion of the medium dose of tagatose (0.833 g / d / kg) and the high dose of tagatose (2.5 g / d / kg) was significantly reduced by 97.3 and 132.2 minutes ( Figure 2 in Figure A); the number of feces was significantly increased by 14 and 19 ( Figure 2 in Figure B), and the fecal water content was increased by 14% and 15% respectively ( Figure 2In C). Compared with the model group, the first defecation time of Lactobacillus paracasei ZYhyy-004 at low dose (1 - 3×10 7 CFU / d / kg), medium dose (1 - 3×10 8 CFU / d / kg) and high dose (1 - 3×10 9 CFU / d / kg) was significantly reduced by 55, 89.2 and 97.6 minutes respectively ( Figure 2 In A); the number of fecal pellets increased significantly by 18, 17 and 21 pellets ( Figure 2 In B), and the fecal water content increased significantly by 2.11%, 4.77% and 15% respectively ( Figure 2 In C). It indicates that Lactobacillus paracasei ZYhyy-004 has the effect of improving constipation in mice, and the high dose of tagatose (2.5 g / d / kg) has the best effect on improving constipation in mice.

[0066] As Figure 3 shown by the results, compared with Lactobacillus casei strain Shirota (LcS) (1 - 3×10 8 CFU / d / kg), Lactobacillus paracasei ZYhyy-004 (1 - 3×10 8 CFU / d / kg) significantly reduced the first defecation time by 28.3 minutes ( Figure 3 In A), the number of fecal pellets in mice increased significantly by 8 pellets at 2 hours ( Figure 3 In B), and there was no difference in fecal water content ( Figure 3 In C) and small intestine propulsion rate ( Figure 3 In D). The above results indicate that Lactobacillus paracasei ZYhyy-004 (1 - 3×10 8 CFU / d / kg) is superior to Lactobacillus casei strain Shirota (LcS) (1 - 3×10 8 CFU / d / kg) in improving constipation in mice.

[0067] As Figure 3 shown by the results, after co-intervention of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) on constipated mice for 14 days, the constipation symptoms of mice were significantly improved. Compared with the model group, the first defecation time was significantly reduced by 161 minutes ( Figure 3 In A); the number of fecal pellets increased significantly by 29 pellets ( Figure 3 In B), and the fecal water content increased significantly by 28% at the same time ( Figure 3In C), and there was no significant difference in the effect compared with the blank group. After co-intervening with Lactobacillus paracasei strain Shirota (LcS) and tagatose (0.833 g / d / kg) on constipated mice for 14 days, the constipation symptoms of the mice were also significantly improved. Compared with the model group, the first red feces excretion time was significantly reduced by 135 minutes ( Figure 3 In A); the number of fecal pellets was significantly increased by 14 ( Figure 3 In B), and at the same time, the fecal water content was significantly increased by 8% ( Figure 3 In C), but its intervention effect did not reach the intervention effect of the drug group. It is indicated that the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) is superior to the combination of Lactobacillus paracasei strain Shirota (LcS) and tagatose (0.833 g / d / kg) in improving constipation in mice.

[0068] Example 4: Determination of the small intestine propulsion rate experiment in mice

[0069] On the 30th day, the mice in each group were fasted overnight without water deprivation. At 8 am on the 31st day, the blank group was given 0.1 mL of 0.9% saline solution, and the model group and the gavage bacteria group were both given 0.1 mL of loperamide hydrochloride solution (15 mg / kg b.w). After 30 minutes, the blank group and the model group were gavaged with 0.6% (m:v) carmine, and the gavage bacteria group was gavaged with carmine containing their respective gavage contents. After 30 minutes, the mice were sacrificed, the abdominal cavity was opened, and the upper part was cut from the pylorus and the lower part to the cecum. The total length of the small intestine was measured as the "total length of the small intestine", and the length from the pylorus to the carmine front was the "carmine propulsion length". The small intestine propulsion rate was calculated according to formula (2):

[0070] Small intestine propulsion rate / % = Carmine propulsion length (cm) / Total length of small intestine (cm) × 100% (2)

[0071] As Figure 3 Shown in the result of D), after co-intervening with the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) on constipated mice for 14 days, compared with the model group, the small intestine propulsion rate was significantly increased by 2.7 times, and there was no difference compared with the blank group. The propulsion rate of the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) was not different from that of Lactobacillus paracasei ZYhyy-004, tagatose alone, and the combination of Lactobacillus paracasei strain Shirota (LcS) and tagatose (0.833 g / d / kg).

[0072] As Figure 4As shown by the results, the CompuSyn software was used to analyze the defecation time of Lactobacillus paracasei ZYhyy-004, Lactobacillus paracasei subsp. paracasei strain LcS, and tagatose alone and in combination in constipated mice. When the obtained CI was greater than 1, it indicated inhibition; when CI = 1, it indicated addition; when CI was less than 1, it indicated promotion. The CI of the combination of Lactobacillus paracasei ZYhyy-004 (1 - 3×10 8 CFU / d / kg) and tagatose (0.833 g / d / kg) was 0.838 ( Figure 4 in A), while the CI of the combination of Lactobacillus paracasei subsp. paracasei strain LcS (1 - 3×10 8 CFU / d / kg) and tagatose (0.833 g / d / kg) was 1.150 ( Figure 4 in B). The results showed that the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) had a promoting effect on intervening in constipated mice, while the combination of Lactobacillus paracasei subsp. paracasei strain LcS (1 - 3×10 8 CFU / d / kg) and tagatose (0.833 g / d / kg) had an inhibitory effect on intervening in constipated mice.

[0073] In summary, single Lactobacillus paracasei ZYhyy-004 or tagatose, as well as the Lactobacillus paracasei ZYhyy-004 + tagatose combination, can all treat functional constipation by increasing the number of fecal pellets and fecal water content, reducing defecation time, and increasing the small intestine propulsion rate. However, it should be noted that after the combination of Lactobacillus paracasei ZYhyy-004 and tagatose, the intervention effect on improving mouse constipation was significantly better than that of single Lactobacillus paracasei ZYhyy-004 or tagatose, and a synergistic effect was achieved.

[0074] Finally, it should be noted that the above is only used to illustrate the technical solution of the present invention and not to limit it. Although the present invention has been described in detail with reference to the preferred arrangement, those of ordinary skill in the art should understand that the technical solution of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solution of the present invention.

Claims

1. A composition of Lactobacillus paracasei and tagatose that can synergistically treat functional constipation, characterized in that: The active ingredients of the composition are Lactobacillus paracasei ZYhyy-004 and tagatose; Lactobacillus paracasei was named ZYhyy-004, which was deposited in the General Microbiology Center of the China Microbiological Culture Management Committee and classified as Lacticaseibacillus paracasei The deposit number is CGMCC No. 31554, and the deposit date is August 5, 2024.

2. The Lactobacillus paracasei and tagatose composition according to claim 1, characterized in that In the composition, the final therapeutic dose of Lactobacillus paracasei named ZYhyy-004 is not less than 1.0-3.0×10 7 CFU / d / kg body weight.

3. The Lactobacillus paracasei and tagatose composition according to claim 1, characterized in that In the composition, the final therapeutic dose of tagatose is 0.167-2.5 g / d / kg body weight.

4. The Lactobacillus paracasei and tagatose composition according to any one of claims 1 to 3, characterized in that The dosage form of the composition includes lyophilized powder, capsule, tablet or granule.

5. Use of the composition according to any one of claims 1 to 3 in the preparation of a medicament for treating and / or improving functional constipation.

6. The use according to claim 5, characterized in that The medicine is one or more of the following: (1) The drug can reduce the time of defecation; (2) The drug can increase the number of fecal particles; (3) The drug can increase the water content of feces; (4) The drug can increase the small intestinal propulsion rate.

7. A probiotic composition, characterized in that: A composition comprising Lactobacillus paracasei and tagatose for synergistically treating functional constipation as described in any one of claims 1 to 4.

8. The probiotic composition according to claim 7, characterized in that The probiotic composition also includes a medically acceptable carrier.

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