Lactobacillus paracasei and tagatose composition capable of synergistically treating functional constipation

Abstract

The invention relates to the technical field of microorganisms and food biology, and provides a lactobacillus paracasei and tagatose composition capable of synergistically treating functional constipation, the active ingredients of the composition are lactobacillus paracasei ZYhyy-004 and tagatose, the lactobacillus paracasei is named as ZYhyy-004, the tagatose is named as ZYhyy-004, the tagatose is named as ZYhyy-004, and the tagatose is named as ZYhyy-004. The strain is preserved in the China General Microbiological Culture Collection Center (CGMCC), the classification name of the strain is Lacticaseibacillus paracasei, the preservation number of the strain is CGMCC No.31554, and the preservation date of the strain is August 5, 2024. Experiments prove that in the composition of the lactobacillus paracasei and the tagatose, the lactobacillus paracasei ZYhyy-004 and the tagatose have a synergistic effect in treating and / or improving the functional constipation of animals, and can be used for improving or treating the functional constipation.

Description

Technical Field

[0001] The invention belongs to the field of microorganism and food biotechnology, and particularly relates to a Lactobacillus paracasei and tagatose composition capable of synergistically treating functional constipation. Background Art

[0002] Under the shadow of the modern fast-paced lifestyle, constipation has become a common problem affecting public health. The process of urbanization has led to a significant reduction in people's daily exercise. The excessive intake of high-oil, high-fat, and finely processed foods, coupled with the decline in physical functions caused by aging, has caused the incidence of constipation to rise year by year. Globally, different regions and age groups are deeply troubled by it. The prevalence of chronic constipation in the young and middle-aged groups can reach about 15% due to work pressure and poor work and rest, while the elderly group is affected by factors such as slowed intestinal peristalsis, and this proportion is as high as 30% or more. Constipation causes far more than just visual discomfort such as difficulty in defecation and abdominal distension. Long-term accumulation will also interfere with the normal absorption and excretion function of the intestine, damage the intestinal mucosal barrier, and is closely related to the increased risk of serious diseases such as intestinal inflammation and colorectal cancer, which has driven the scientific research and medical community to accelerate the exploration of efficient prevention and treatment strategies.

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

[0004] In view of the problems existing in the prior art, the purpose of the present invention is to screen and obtain Lactobacillus paracasei and tagatose compositions that can be used in combination with tagatose to provide a synergistic treatment of functional constipation. The combined use of probiotics and tagatose can not only improve intestinal motility with the help of the direct regulatory effect of probiotics, but also use tagatose to create favorable living and breeding conditions for probiotics. This two-pronged approach creates a new path for constipation treatment that is both targeted and sustainable, and has great potential in the fields of functional foods, nutritional supplements, and even clinical auxiliary treatments.

[0005] With its excellent acid and bile resistance, Lactobacillus paracasei stands out in the "difficult journey" of the intestine. It can smoothly reach the intestine and firmly adhere to colonization, continuously secrete active substances such as bacteriocins and lactic acid, regulate the pH value of the intestine, inhibit the growth of harmful bacteria, and interact with intestinal epithelial cells to activate the neuroendocrine network in the intestine, helping the intestine to move regularly. Combined with the known properties of tagatose, the inventor conducted a study, hoping to find a strain of Lactobacillus paracasei that can be used in combination with tagatose to achieve synergistic effects to promote intestinal health. The Lactobacillus paracasei screened in the early stage of the study include: Lactobacillus paracasei ZYhyy-004 and Lactobacillus paracasei Shirota strain (LcS). However, the experimental results show that the above two strains of Lactobacillus paracasei can improve constipation symptoms when intervened alone, but the combination of Lactobacillus paracasei Shirota strain (LcS) and tagatose has an inhibitory effect on the intervention of constipation mice; Lactobacillus paracasei ZYhyy-004 and tagatose are used in combination, which shows a promoting effect. In view of this, the inventor provides the following solution of the present invention.

[0006] In order to achieve the above-mentioned object, the first aspect of the present invention provides a strain of Lactobacillus paracasei capable of preventing and treating functional constipation, named ZYhyy-004, which is deposited in the General Microbiological Center of China National Microbiological Culture Collection Committee and is classified as Lacticaseibacillus paracasei The deposit number is CGMCC No. 31554, and the deposit date is August 5, 2024.

[0007] The second aspect of the present invention provides a composition of Lactobacillus paracasei and tagatose that can synergistically treat functional constipation, wherein the active ingredients of the composition are Lactobacillus paracasei and tagatose; Lactobacillus paracasei was named ZYhyy-004, which was deposited in the General Microbiology Center of China Microbiological Culture Collection Administration and classified as Lacticaseibacillus paracasei The deposit number is CGMCC No.31554, and the deposit date is August 5, 2024.

[0008] Furthermore, in the composition, the final therapeutic dose of Lactobacillus paracasei named ZYhyy-004 is a viable bacterial count of not less than 1.0-3.0×10 7 CFU / d / kg body weight.

[0009] Furthermore, in the composition, the final therapeutic dose of tagatose is 0.167-2.5 g / d / kg body weight.

[0010] Furthermore, the dosage form of the composition includes lyophilized powder, capsule, tablet or granule.

[0011] The third aspect of the present invention provides use of the Lactobacillus paracasei described in the first aspect or the composition described in the second aspect in preparing a product for treating and / or improving functional constipation.

[0012] Furthermore, the product is a medicine.

[0013] Furthermore, 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.

[0014] The fourth aspect of the present invention provides a probiotic composition, comprising the Lactobacillus paracasei described in the first aspect, or the Lactobacillus paracasei and tagatose composition capable of synergistically treating functional constipation described in the second aspect.

[0015] Furthermore, the probiotic composition also includes a medically acceptable carrier.

[0016] Strain deposit information:

[0017] Lactobacillus paracasei was named ZYhyy-004, and the strain was deposited in the General Microbiology Center of China Microbiological Culture Collection Administration (CGMCC), address: No. 3, Yard No. 1, Beichen West Road, Chaoyang District, Beijing; Lacticaseibacillus paracasei The deposit number is CGMCC No. 31554, and the deposit date is August 5, 2024.

[0018] Compared with the prior art, the present invention has the following beneficial effects:

[0019] 1. This application screened and obtained a probiotic strain that can prevent and treat functional constipation. The strain was identified as Lactobacillus paracasei, with a preservation number of CGMCC No. 31554 and a classification name of Lacticaseibacillus paracasei .

[0020] 2. The Lactobacillus paracasei ZYhyy-004 described in the present application can effectively increase the number of stool particles and the water content of stool, reduce the defecation time, and improve the small intestinal propulsion rate to achieve the treatment of functional constipation. Its effect is significantly better than the Lactobacillus paracasei Shirota strain (LcS) that has been developed and marketed.

[0021] 3. This application discovered for the first time that the combined use of tagatose and Lactobacillus paracasei ZYhyy-004 has a better intervention effect on improving constipation in mice than the intervention effects of Lactobacillus paracasei ZYhyy-004 and 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 source for Lactobacillus paracasei, ensuring its vigorous metabolic activity and increasing the number of survival in the intestine. On the other hand, the two work together to optimize the structure of intestinal microbial communities, improve the intestinal biochemical environment, and regulate intestinal nerve conduction in multiple dimensions to overcome the problem of constipation in all directions. It is expected to fill the gap in existing constipation treatment methods with its natural, safe and efficient advantages, and become a cutting-edge combination for intestinal health management in the future, serving the vast number of people suffering from constipation. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] The present invention will be further described below in conjunction with the accompanying drawings and embodiments: Figure 1 The figure shows the successful results of the functional constipation mouse model; A is the time of the first red pellet, B is the number of feces pellets in 2 hours, and C is the water content of feces; Figure 2 The results of treating functional constipation mice with different doses of Lactobacillus paracasei ZYhyy-004 and different doses of tagatose are shown; A is the time of first red pellet discharge, B is the number of feces pellets in 2 hours, and C is the water content of feces; Figure 3 The results show that the expression of Lactobacillus paracasei ZYhyy-004 and tagatose was 1~3×10 8 Results of treating functional constipation mice after the combination of CFU / d / kg and 2.5 g / d / kg; A is the time of first red pellet excretion, B is the number of fecal pellets in 2 hours, C is the fecal water content, and D is the intestinal propulsion rate; Figure 4 The results show that the expression of Lactobacillus paracasei and tagatose was 1~3×10 8 The synergistic enhancement results after the combination of 2.5 CFU / d / kg and 2.5 g / d / kg (combined normalized equivalent hologram); where A is Lactobacillus paracasei ZYhyy-004 and B is Lactobacillus paracasei Shirota strain (LcS). DETAILED DESCRIPTION

[0023] The implementation of the present invention is not limited to the following embodiments, and any form of modification and / or change made to the present invention will fall within the scope of protection of the present invention. In the present invention, unless otherwise specified, all equipment and raw materials can be purchased from the market or are commonly used in the industry. Unless otherwise specified, the methods used in the embodiments are common techniques in the art.

[0024] For numerical ranges, the endpoints of each range, the endpoints of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be deemed to be specifically disclosed herein.

[0025] In the following examples, Lactobacillus paracasei ZYhyy-004 was sourced from Zhongyuan Food Laboratory; tagatose was sourced from Henan Yihengyuan Biotechnology Co., Ltd. Other chemical reagents were purchased from regular chemical reagent suppliers.

[0026] In the following examples, the culture medium formulations involved include: MRS liquid culture medium, its formula is: 10g / L protein Chen, 5g / L beef powder, 4g / L yeast powder, 2g / L glucose, 1ml / L Tween 80, 2g / L dipotassium hydrogen phosphate, 5g / L sodium acetate, 2g / L triammonium citrate, 0.2g / L magnesium sulfate, 0.05g / L manganese sulfate, distilled water.

[0027] Example 1: Microbial culture and tagatose preparation

[0028] 1) Preparation of Lactobacillus paracasei ZYhyy-004 bacteria: A probiotic strain was isolated and identified as Lactobacillus paracasei Lacticaseibacillus paracasei , deposited in the General Microbiology Center of China Microorganism Culture Collection Administration (CGMCC), with the deposit number CGMCC No. 31554 and the deposit date of August 5, 2024.

[0029] The isolated Lactobacillus paracasei ZYhyy-004 was subcultured twice in MRS liquid medium, inoculated into 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.

[0030] 2) Preparation of Lactobacillus paracasei strain Shirota (LcS): 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.

[0031] 3) Preparation of tagatose intragastric solution: 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.

[0032] Example 2: Animal Experiment

[0033] 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: The experimental animals used were SPF-grade BALB / c (6-week-old, female) mice purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0034] 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.

[0035] 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.

[0036] The blank group was gavaged with 0.9% saline until the end of the experiment; Model group and intervention groups: First, gavage 0.1mL 15mg / kg bw loperamide hydrochloride until the model is successful (7-14 days). After the model is successfully established, the model group and intervention group are gavaged with 0.1mL 15mg / kg bw loperamide hydrochloride every other day until the end of the experiment; at the same time, the drug group is gavaged with polyethylene glycol 4000 powder.

[0037] Each intervention group (gavage volume was 0.1 mL, gavage for 2-3 weeks): Tagatose high-dose group, tagatose medium-dose group, and tagatose low-dose group: low, medium, and high doses of tagatose were gavaged orally, respectively (low dose 0.167 g / d / kg, medium dose 0.833 g / d / kg, high dose 2.5 g / d / kg); The low-dose group, medium-dose group, and high-dose group of Lactobacillus paracasei ZYhyy-004 were 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); Lactobacillus paracasei Shirota strain (LcS) group: 1-3×10 8 CFU / d / kg of Lactobacillus paracasei Shirota strain (LcS); Lactobacillus paracasei ZYhyy-004 + tagatose medium-dose mixed group: 1-3×10 8 CFU / d / kg of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg); Lactobacillus paracasei Shirota strain (LcS) + medium-dose tagatose mixed group: 1-3×10 8 CFU / d / kg of Lactobacillus paracasei strain Shirota (LcS) and tagatose (0.833 g / d / kg).

[0038] Example 3: Detection of fecal water content, number of stool particles within 2 hours and time of first red stool particle

[0039] This example measured the fecal water content, the number of stool pellets within 2 hours and the time of the first red stool pellet in each group of the animal experiment in Example 2. The specific method and results are as follows: Determination of fecal water content: On the 29th day, after gavage, mice were placed individually in a cage lined with absorbent paper to collect feces. The wet weight was obtained by weighing, and the dry weight was obtained after freeze-drying. The fecal water content was calculated according to formula (1): Fecal moisture content / % = (fecal wet weight - fecal dry weight) / fecal wet weight × 100% (1)

[0040] Number of stool particles within 2 hours: On the 30th day, the blank group was given 0.1 mL of 0.9% saline, and the model group and intervention group were given 0.1 mL of loperamide hydrochloride solution (15 mg / kg bw). After 1 hour, each mouse was placed in a cage lined with absorbent paper, and feces were collected every 30 minutes for a total of 2 hours.

[0041] Time of first red stool: On the 30th day, the blank group was given 0.1 mL 0.9% saline, and the model group and intervention group were given 0.1 mL loperamide hydrochloride solution (15 mg / kg bw). One hour later, each group was gavaged with 0.1 mL 0.6% (m:v) carmine. Starting from the gavage of carmine, the time of the first red stool for each mouse was recorded.

[0042] like Figure 1 The results showed that 7 days after modeling, the time to first red pellet excretion, number of feces pellets and feces water content of 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.

[0043] The performance of the intervention group was compared with that of the model group, e.g. Figure 2 The results showed that after 14 days of intervention with different doses of tagatose, low-dose tagatose (0.167 g / d / kg), medium-dose tagatose (0.833 g / d / kg), high-dose tagatose (2.5 g / d / kg), and low-dose Lactobacillus paracasei ZYhyy-004 (1-3×10 7 CFU / d / kg), Lactobacillus paracasei ZYhyy-004 medium dose (1~3×10 8 CFU / d / kg), Lactobacillus paracasei ZYhyy-004 high dose (1~3×10 9 CFU / d / kg) showed improvement in the first red pellet excretion time, stool pellet number and stool water content. Compared with the model group, the first red pellet excretion time of medium-dose tagatose (0.833 g / d / kg) and high-dose tagatose (2.5 g / d / kg) was significantly reduced by 97.3 and 132.2 minutes, respectively ( Figure 2 Middle A); the number of fecal particles increased significantly by 14 and 19 particles ( Figure 2 B), while increasing fecal water content by 14% and 15% ( Figure 2 Compared with the model group, low doses of Lactobacillus paracasei ZYhyy-004 (1-3×10 7 CFU / d / kg), Lactobacillus paracasei ZYhyy-004 medium dose (1~3×10 8 CFU / d / kg and high doses of Lactobacillus paracasei ZYhyy-004 (1~3×10 9 CFU / d / kg) were significantly reduced by 55, 89.2 and 97.6 minutes, respectively ( Figure 2 Middle A); the number of fecal particles increased significantly by 18, 17 and 21 particles ( Figure 2 B), while significantly increasing the fecal water content by 2.11%, 4.77% and 15% ( Figure 2C). This indicates that Lactobacillus paracasei ZYhyy-004 has the effect of improving constipation in mice, and high dose of tagatose (2.5 g / d / kg) has the best effect on improving constipation in mice.

[0044] like Figure 3 The results showed that the Lactobacillus paracasei strain Shirota (LcS) (1-3×10 8 CFU / d / kg) compared with Lactobacillus paracasei ZYhyy-004 (1~3×10 8 CFU / d / kg) significantly reduced the time to first redness by 28.3 minutes ( Figure 3 Middle A), the number of fecal particles in mice increased significantly by 8 particles at 2 hours ( Figure 3 Middle B), fecal water content ( Figure 3 C) and small intestinal propulsion rate ( Figure 3 The above results show that Lactobacillus paracasei ZYhyy-004 (1~3×10 8 CFU / d / kg) was superior to Lactobacillus paracasei Shirota strain (LcS) (1~3×10 8 CFU / d / kg).

[0045] like Figure 3 The results showed that after 14 days of co-intervention of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) in constipated mice, the constipation symptoms of mice were significantly improved. Compared with the model group, the time to first red pill was significantly reduced by 161 minutes ( Figure 3 Middle A); the number of fecal particles increased significantly by 29 ( Figure 3 B), and significantly increased the fecal water content by 28% ( Figure 3 C), and the effect was not significantly different from the blank group. After 14 days of intervention with Lactobacillus paracasei Shirota strain (LcS) and tagatose (0.833g / d / kg) in constipated mice, the constipation symptoms of mice were also significantly improved. Compared with the model group, the time to first red pill was significantly reduced by 135 minutes ( Figure 3 Middle A); the number of fecal particles increased significantly by 14 ( Figure 3 B), while significantly increasing the fecal water content by 8% ( Figure 3 C), but its intervention effect did not reach the intervention effect of the drug group. This shows that the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) is better than the combination of Lactobacillus paracasei Shirota strain (LcS) and tagatose (0.833 g / d / kg) in improving constipation in mice.

[0046] Example 4: Determination of mouse small intestinal propulsion rate experiment

[0047] On the 30th day, mice in each group were fasted overnight but not water-deprived. At 8:00 a.m. on the 31st day, the blank group was given 0.1 mL of 0.9% saline solution, and the model group and the bacterial injection group were given 0.1 mL of loperamide hydrochloride solution (15 mg / kg bw). 30 minutes later, the blank group and the model group were gavaged with 0.6% (m:v) carmine, and the bacterial injection group was gavaged with carmine containing the respective gavage contents. After 30 minutes, the mice were killed, the abdominal cavity was opened, and the upper end from the pylorus to the lower end to the cecum was cut off. 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 front of the carmine was the "carmine advancement length". The small intestine advancement rate was calculated according to formula (2): Small intestinal propulsion rate / % = Carmine propulsion length (cm) / total small intestinal length (cm) × 100% (2)

[0048] like Figure 3 The results in middle D show that after 14 days of co-intervention of constipation mice with the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg), the small intestinal propulsion rate increased significantly by 2.7 times compared with the model group, and there was no difference 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 the single substance of Lactobacillus paracasei ZYhyy-004 and tagatose, and the combination of Lactobacillus paracasei Shirota strain (LcS) and tagatose (0.833 g / d / kg).

[0049] like Figure 4 The results showed that CompuSyn software was used to analyze the red discharge time of constipated mice treated with Lactobacillus paracasei ZYhyy-004, Lactobacillus paracasei Shirota strain (LcS) and tagatose alone or together. The CI greater than 1 indicated inhibition; CI = 1 indicated addition; CI less than 1 indicated promotion. 8 CFU / d / kg) and tagatose (0.833 g / d / kg) combined with CI = 0.838 ( Figure 4 A), while Lactobacillus paracasei Shirota strain (LcS) (1~3×10 8 CFU / d / kg) and tagatose (0.833 g / d / kg) combined with CI = 1.150 ( Figure 4 The results showed that the combination of Lactobacillus paracasei ZYhyy-004 and tagatose (0.833 g / d / kg) promoted the intervention of constipation in mice, while Lactobacillus paracasei Shirota strain (LcS) (1-3 × 10 8 CFU / d / kg) and tagatose (0.833 g / d / kg) had an inhibitory effect on the intervention of constipation in mice.

[0050] In summary, single Lactobacillus paracasei ZYhyy-004 or tagatose, as well as the combination of Lactobacillus paracasei ZYhyy-004 and tagatose, can treat functional constipation by increasing the number of fecal particles and fecal water content, reducing defecation time, and improving small intestinal propulsion rate. However, it is worth noting that the intervention effect of Lactobacillus paracasei ZYhyy-004 combined with tagatose in improving constipation in mice is significantly better than the intervention effect of Lactobacillus paracasei ZYhyy-004 and tagatose alone, and has a synergistic effect.

[0051] Finally, it should be noted that the above is only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention has been described in detail with reference to the preferred arrangement scheme, a person skilled in the art should understand that the technical solution of the present invention may be modified or replaced by equivalents 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 China Microbiological Culture Collection Administration 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 product for treating and / or improving functional constipation.

6. The use according to claim 5, characterized in that The product described is a pharmaceutical product.

7. The use according to claim 6, 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.

8. 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.

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

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