Lactobacillus plantarum AL4510, microbial agent and application of lactobacillus plantarum AL4510 in preparation of medicine for relieving altitude stress and / or intestinal injury induced by low-pressure and low-oxygen environment

Abstract

The invention provides lactobacillus plantarum AL4510, a microbial agent and application of the lactobacillus plantarum AL4510 to preparation of a medicine for relieving altitude stress and / or intestinal injury induced by a low-pressure and low-oxygen environment, and relates to the technical field of microorganisms. The lactobacillus plantarum AL4510 provided by the invention is preserved in the China Center for Type Culture Collection, the preservation address is Wuhan University, Wuhan, China, the preservation date is March 10, 2025, and the preservation number is CCTCC NO: M 2025421. The lactobacillus plantarum AL4510 strain has a unique strong probiotic function of plateau lactic acid bacteria and relatively strong oxidation resistance, gastrointestinal fluid tolerance and safety, and can better relieve altitude stress and intestinal injury by reducing the oxidative stress level and inflammatory factors and regulating intestinal flora.

Description

Technical Field

[0001] The present invention relates to the technical field of microorganisms, and in particular to a Lactobacillus plantarum AL4510, a microbial agent, and their application in the preparation of a drug for alleviating altitude sickness and / or intestinal injury induced by a low-pressure and low-oxygen environment. Background Art

[0002] High-altitude hypoxia is an important environmental stress faced by the human body. Long-term exposure to the hypoxic and low-pressure environment in high-altitude areas requires the body to undergo a series of complex physiological adaptation processes to maintain the body's homeostasis and improve the tolerance to the hypoxic environment. The altitude of the Qinghai-Tibet Plateau is usually between 3000 and 5000 meters, with thin air, low air pressure, and a significant decrease in the partial pressure of oxygen. Under the combined action of these factors, the human body will be subjected to significant hypoxic stress when living or being exposed to the plateau for a short time.

[0003] Low-pressure hypoxia can lead to changes in the oxygen transport chain from the external air to the mitochondrial membrane, thereby activating a series of compensatory physiological mechanisms to adapt to the hypoxic environment. However, long-term or acute exposure to low-pressure hypoxia may induce a series of altitude-related diseases, including acute mountain sickness (AMS) such as high-altitude pulmonary edema (HAPE), high-altitude cerebral edema (HACE), and high-altitude pulmonary hypertension (HAPH). In addition, AMS is often accompanied by gastrointestinal symptoms such as loss of appetite, abdominal distension, indigestion, and infectious diarrhea.

[0004] Studies have shown that acute and chronic low-pressure hypoxia can lead to an increase in the production of oxidative stress biomarkers such as reactive oxygen species (ROS) and reactive nitrogen species (RONS), and hypoxia-induced oxidative stress can cause damage to the structures of lipids, proteins, and DNA, thereby affecting multiple tissues and organs, especially the intestine. Under a hypoxic environment, oxidative stress and inflammatory responses will damage the intestinal barrier function, leading to the translocation of bacteria and endotoxins, and ultimately may trigger high-altitude multiple organ dysfunction syndrome (HMODS), posing a serious threat to the health of the body.

[0005] In recent years, studies have shown that probiotics, especially probiotics with antioxidant and anti-inflammatory properties, can significantly reduce oxidative stress damage and inflammatory responses. Probiotic-based interventions have shown good prospects in regulating the homeostasis of the gut microbiota, improving intestinal barrier function, and regulating inflammatory responses. Probiotic intervention has become a potential effective strategy for coping with high-altitude hypoxia in recent years, especially showing great potential in alleviating oxidative stress and inflammatory responses.

[0006] The unique geographical and climatic environment of the Qinghai-Tibet Plateau has given birth to rich microbial resources. In order to adapt to the special plateau environment, plateau animals have formed unique intestinal microbial communities. These microbial communities not only possess unique biological characteristics and genetic diversity, but also become precious and unique microbial germplasm resources under global extreme environmental conditions. Therefore, protecting and developing these high-quality bacterial species resources, establishing a characteristic bacterial species resource library in the plateau region, and screening out bacterial species with regional characteristics and unique biological activities are of great significance for in-depth research on the antioxidant characteristics and applications of plateau bacterial species. Summary of the Invention

[0007] The object of the present invention is to provide a Lactobacillus plantarum AL4510, which has a strong probiotic function unique to plateau lactic acid bacteria, as well as strong antioxidant capacity, gastrointestinal fluid tolerance and safety. It can better relieve altitude sickness and intestinal injury induced by low pressure and low oxygen by alleviating oxidative stress, inflammatory response and regulating the intestinal flora.

[0008] In order to achieve the above object of the invention, the present invention provides the following technical solutions:

[0009] The present invention provides a Lactobacillus plantarum AL4510, which is preserved in the China Center for Type Culture Collection, the preservation address is Wuhan University, Wuhan, China, the preservation date is March 10, 2025, and the preservation number is CCTCC NO: M 2025421.

[0010] The present invention also provides a microbial inoculum with the above Lactobacillus plantarum AL4510 as the main active ingredient.

[0011] Preferably, the bacterial concentration of Lactobacillus plantarum AL4510 in the microbial inoculum is (0.5-2)×10 9 CFU / mL.

[0012] The present invention also provides the application of the above Lactobacillus plantarum AL4510 or the microbial inoculum in the preparation of drugs for relieving altitude sickness and / or intestinal injury.

[0013] Preferably, the altitude sickness and / or intestinal injury is induced by simulating a low-pressure and low-oxygen environment at an altitude of 5000 m in a low-pressure oxygen chamber;

[0014] The air pressure of the low pressure is: 50-54 kPa;

[0015] The oxygen content of the low oxygen is: 11.0-11.5%.

[0016] By adopting the above technical solutions, the present invention has the following beneficial effects:

[0017] The Lactobacillus plantarum AL4510 of the present invention is screened from the Qinghai-Tibet Plateau region and has powerful probiotic functions unique to plateau lactic acid bacteria, with strong antioxidant capacity, gastrointestinal fluid tolerance and safety. The Lactobacillus plantarum AL4510 can promote intestinal health by alleviating oxidative stress and inflammation of the body, enhancing intestinal barrier function and regulating intestinal homeostasis; it can also regulate the intestinal flora, maintain the homeostasis of the intestinal microecology, thereby alleviating altitude sickness and intestinal damage induced by the low-pressure and low-oxygen environment.

[0018] Examples of the present invention show that Lactobacillus plantarum L.plantarum AL4510 can effectively reduce the increase in pulmonary artery pressure and oxidative stress response induced by the low-pressure and low-oxygen environment, thereby alleviating ileal tissue inflammation, goblet cell loss and villus reduction, enhancing the expression of claudin-1, occludin and ZO-1 in the ileal epithelium, alleviating intestinal damage in low-pressure and low-oxygen mice, and protecting their intestinal barrier. L.plantarum AL4510 regulates the structure of intestinal microorganisms in low-pressure and low-oxygen mice by reducing the abundance of potentially harmful bacteria (Chlamydia, Alistipes) and increasing the abundance of beneficial bacteria (Akkermansi and Lactobacillus) in the intestines of low-pressure and low-oxygen mice, and increasing the content of its metabolite SCFAs to slow down intestinal damage and inflammation levels and promote intestinal barrier function. Brief Description of the Drawings

[0019] Figure 1 is the colony morphology of strain L.plantarum AL4510;

[0020] Figure 2 is the phylogenetic tree of strain L.plantarum AL4510;

[0021] Figure 3 are the contents of GSH, T-AOC, and MDA in the sera of mice in different groups. A is the content of GSH, B is the content of T-AOC, and C is the content of MDA;

[0022] Figure 4 is the pulmonary artery pressure of mice in different groups;

[0023] Figure 5 are the HE and PAS-AB staining conditions of the ileal tissues of mice in different groups;

[0024] Figure 6 are the immunofluorescence expression results of claudin-1, occludin, and ZO-1 in mice in different groups;

[0025] Figure 7The contents of IL-6, IL-1β, and TNF-α in the ileum tissues of mice in different groups. A is the content of IL-6, B is the content of IL-1β, and C is the content of TNF-α;

[0026] Figure 8 The contents of SCFAs in the colonic contents of mice in different groups. A is the content of acetic acid, B is the content of propionic acid, and C is the content of butyric acid;

[0027] Figure 9 The Alpha diversity of the intestinal microbiota of mice in different groups. A is the Shannon index, and B is the Simpson index;

[0028] Figure 10 The Beta diversity of the intestinal microbiota of mice in different groups;

[0029] Figure 11 The phylum level of the intestinal microbiota of mice in different groups;

[0030] Figure 12 The relative abundances at the genus level of mice in different groups. A is the relative abundance of Lactobacillus, B is the relative abundance of Akkermansi, C is the relative abundance of Adlercreutzia, D is the relative abundance of Alistipes, and E is the relative abundance of Chlamydia.

[0031] Biological deposit description

[0032] The present invention relates to Lactobacillus plantarum AL4510, with the taxonomic name Lactobacillus plantarum, which is deposited in the China Center for Type Culture Collection. The deposit address is Wuhan University, Wuhan, China. The deposit date is March 10, 2025, and the deposit number is CCTCC NO: M 2025421. Detailed implementation manners

[0033] The technical solutions provided by the present invention will be described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0034] Example 1

[0035] A microbial inoculum, the preparation process is as follows:

[0036] Inoculate the AL4510 bacterial solution stored at -80°C into the sterilized MRS medium and culture it at 37°C for 18 h. After continuous activation 3 times, centrifuge at 8000 g and 4°C for 10 min to collect the bacterial cells. After washing 3 times, resuspend them in PBS and adjust the bacterial solution concentration to 1×109 CFU / mL, and it is obtained.

[0037] Example 2 Isolation and Identification of Lactobacillus AL4510

[0038] (I) Obtaining of Lactobacillus plantarum AL4510 and Determination of Its Antioxidant Capacity in Vitro

[0039] Preparation of cell-free extract: Strains (strain 46, strain 40, strain 39, strain 120, and strain AL4510) isolated and screened from dairy products and wild animal fecal samples in the Qinghai-Tibet Plateau region. Then, single colonies were selected from the control strain Lactobacillus rhamnosus GG (LGG) (purchased from Ningbo Biotechnology Co., Ltd.), and they were placed in a constant temperature incubator at 37°C for 18 h. After continuous activation 3 times, the cells were collected by centrifugation at 13,000 rpm for 10 min. After washing three times with PBS, they were resuspended, and the cell suspension concentration was adjusted to 1×10 9 CFU / mL. The samples were ultrasonically treated on ice for 30 min at a frequency of 360 W, centrifuged, and the supernatant was collected as the cell-free extract.

[0040] 1. Determination of DPPH scavenging ability: Take 1 mL of the sample to be tested, add 1 mL of 0.2 mmol / L DPPH anhydrous ethanol solution, mix well, and let it react in the dark at room temperature for 30 min. Centrifuge at 6,000 rpm for 10 min, and measure the absorbance of the supernatant at a wavelength of 517 nm.

[0041] 2. Determination of OH radical scavenging ability: Add 0.5 mL of the sample, 1 mL of PBS, 1 mL of 2.5 mmol / L FeSO4, and 1 mL of 20 mmol / L H2O2 to 1 mL of O-phenanthroline (concentration of 0.1%). After reacting in a constant temperature water bath at 37°C for 1.5 h, measure the absorbance at 536 nm.

[0042] 3. O2 - Scavenging ability determination: Take 2.8 mL of Tris-HCl (0.05 mol / L, pH 8.2) and place it in a test tube. Add 0.1 mL of pyrogallol (0.05 mol / L) and 0.1 mL of the sample. After mixing, react at 25°C in the dark for 4 min. Then add 1 mL of 8 mol / L HCl to terminate the reaction, and detect the absorbance at 320 nm.

[0043] 4. Determination of reducing ability: Take 0.5 mL of the sample and place it in a test tube. Add 0.5 mL of a phosphate buffer solution with a concentration of 0.2 mol / L and a pH of 6.6, then add 0.5 mL of 1% potassium ferricyanide. After water bath at 50 °C for 20 min, quickly cool it in an ice bath. Then add 0.5 mL of 10% trichloroacetic acid, centrifuge at 4000 r / min for 10 min. Take 1 mL of the supernatant, add 1 mL of distilled water and 1 mL of 0.1% ferric chloride, and mix evenly. Let it stand at room temperature for 10 min, and measure its absorbance at a wavelength of 700 nm. The results are shown in Table 1.

[0044] In the present invention, the strains 46, 40, 39, 120 and AL4510 are all strains screened by the inventors from the Qinghai-Tibet Plateau region, and the corresponding strain names are named by the inventors themselves.

[0045] Table 1 Determination of antioxidant capacity in the supernatant of different groups

[0046]

[0047] Oxidative stress is a physiological phenomenon caused by the excessive production of free radicals and the imbalance of antioxidant defense, which plays a core role in the occurrence and development of various diseases. By regulating through antioxidant enzymes and non-enzymatic antioxidants, oxidative stress can be effectively regulated, the damage to the body can be reduced, and thus health can be maintained. The plateau environment (low oxygen, low air pressure, strong ultraviolet rays, low temperature, etc.) can lead to an increase in the level of oxidative stress in the body, thereby affecting intestinal barrier function, microbial community homeostasis, and immune regulation, and then causing intestinal injury. Therefore, by comparing the free radical scavenging abilities of different strains, the strain with the strongest antioxidant effect - AL4510 was screened out.

[0048] (2) Identification of Lactobacillus plantarum AL4510

[0049] Observe the colony and cell morphology of the obtained strain AL4510, and conduct physiological and biochemical identification. The results show that: the colony is milky white, round, convex, with relatively regular edges, smooth and moist surface, easy to pick, Gram-positive bacteria, rod-shaped under the microscope, without spores. Catalase negative, oxidase negative. The colony morphology of AL4510 is as Figure 1 shown.

[0050] After extracting the DNA of strain AL4510 using a Gram-positive bacteria genomic DNA extraction kit (purchased from Beijing Solarbio Science & Technology Co., Ltd.), send it to Biomarker Technologies Corporation to clone the 16S rRNA sequence of AL4510 and sequence this 16S rRNA sequence. The sequencing results are compared by BLAST in Genbank to determine the phylogenetic and evolutionary status of AL4510. The phylogenetic tree is as Figure 2As shown, the strain AL4510 was further identified as Lactobacillus plantarum and named Lactobacillus plantarum AL4510.

[0051] Experimental Example 1

[0052] (I) Establishing a mouse model of hypobaric hypoxia

[0053] To evaluate the effects of L. plantarum AL4510 on altitude sickness, ileal injury, ileal tissue inflammation, and gut microbiota in mice, a mouse model of hypobaric hypoxia was established.

[0054] The selected mice were male C57BL / 6J mice, 8 - 9 weeks old, weighing 22 ± 2 g, purchased from the Medical Experimental Center of Lanzhou University. After 7 days of adaptive feeding, the mice were randomly divided into 3 groups (12 mice / group), namely the normobaric normoxia group (N group), the hypobaric hypoxia group (H group), and the hypobaric hypoxia intervention group (L. plantarum AL4510 intervention group, H-AL4510).

[0055] The experimental period was 14 days in total. A hypobaric oxygen chamber (low-pressure oxygen environment control system LP-1500) was used to simulate an altitude of 5000 m. The N group and the H group were given PBS by gavage (200 μL / mouse) + free diet and water, and the H-AL4510 group was given L. plantarum AL4510 by gavage (200 μL / mouse) + free diet and water. The mice in the H group and the H-AL4510 group were continuously housed in the hypobaric hypoxia chamber for 14 days. The hypobaric hypoxia chamber was opened at 9:00 every day to record the diet, water intake, and body weight of the mice. After gavage, the hypobaric hypoxia chamber was closed and the pressure was rapidly increased. First, it was increased to the simulated altitude of 3000 m, and after adapting for 15 minutes, it was raised to 5000 m (air pressure: 54 kPa, oxygen content: 11.3%). On the 15th day, the mice in each group were processed for subsequent experiments.

[0056] (II) L. plantarum AL4510 alleviates oxidative stress induced by hypobaric hypoxia

[0057] The contents of GSH, MDA, and T-AOC in the sera of the mice in each group were measured using detection kits for GSH, T-AOC, and MDA contents, so as to analyze the alleviation of oxidative stress in mice in a hypobaric hypoxia environment by L. plantarum AL4510.

[0058] According to Figure 3It can be seen that compared with the N group, the contents of GSH and T-AOC in the serum of mice in the H group decreased. Compared with the H group, the intervention of L. plantarum AL4510 significantly increased the activities of GSH and T-AOC in the serum of mice in the H-AL4510 group; MDA, as a lipid oxidation product, reflects the degree of oxidative reaction in the body. After hypoxia in mice, its content in the serum was significantly higher than that in the N group (normal), but after the intervention of L. plantarum AL4510, the content of MDA in the serum of mice decreased significantly. It is shown that the intervention of L. plantarum AL4510 can alleviate oxidative stress induced by low pressure and hypoxia.

[0059] (III) Intervention of L. plantarum AL4510 reduces pulmonary artery pressure

[0060] The pulmonary artery pressure of mice was evaluated by a high-frequency small animal photoacoustic imaging system.

[0061] The changes in the pulmonary artery pressure of mice in each group were as Figure 4 shown. Compared with the N group, the pulmonary artery pressure of mice in the H group increased significantly in the simulated plateau environment. After the intervention of L. plantarum AL4510, the pulmonary artery pressure of mice in the H-AL4510 group decreased significantly, indicating that L. plantarum AL4510 can improve the increase in pulmonary artery pressure caused by the plateau environment to a certain extent.

[0062] (IV) L. plantarum AL4510 alleviates ileal pathological damage induced by low pressure and hypoxia in mice

[0063] Pathological sections of ileal tissue can effectively reflect the pathological changes of the ileum in mice. By performing HE staining and AB-PAS staining on the ileal tissue of mice, the villus damage and the loss of goblet cells were observed.

[0064] Take the ileal tissue of mice, fix it in 4% paraformaldehyde solution for 24 h, and dehydrate the colon tissue by soaking it successively in 85%, 95% absolute ethanol and xylene. Then embed it in paraffin and make paraffin sections. Dewax the prepared paraffin sections and perform hematoxylin-eosin staining (HE staining). Stain with hematoxylin for 5 min, rinse with running water, blue back for 10 s, stain with eosin for 5 min, and finally dehydrate and mount the slides. Observe the state of the colon under an optical microscope and collect images. Dewax the prepared paraffin sections to water and stain them according to the instructions of the AB-PAS staining solution kit. After staining, dehydrate and mount the slides. Observe the loss of goblet cells in the colon tissue under the microscope and collect images.

[0065] As Figure 5As shown, the intestinal mucosal folds on the surface of the ileum tissues of N groups of mice were intact, and the structure was not damaged. Moreover, the ileal villi were dense, with normal length and closely arranged, and no pathological damage was observed in the entire ileum tissue. However, compared with the N group, the small intestinal villi in the ileum tissues of the H group of mice were sparse and loosely arranged, the villi length was significantly shortened, and the intestinal mucosa showed atrophy. The ileal crypts became shallow, the goblet cells were significantly reduced, and the intestinal mucosa showed atrophy, and obvious pathological damage occurred in the ileum tissue. However, after the preventive intervention of L. plantarum AL4510, the small intestinal villi significantly increased and were more closely arranged, and the length of the small intestinal villi and the number of goblet cells also increased.

[0066] (V) L. plantarum AL4510 promotes the expression of claudin-1, occludin, and ZO-1 in the ileum tissues of mice under hypobaric hypoxia

[0067] The prepared paraffin sections were dewaxed to water, antigen repaired, and blocked with hydrogen peroxide after drawing circles with a brush for each group. Incubate with BAS for 30 min, add the primary antibody and incubate overnight at 4°C, wash 3 times with PBS, add the corresponding secondary antibody, and incubate at room temperature for 50 min. Wash, add DAPI and incubate for 10 min to counterstain the cell nuclei, and mount with an anti-fluorescence quencher. The sections were observed and images were collected under a fluorescence microscope to determine the expression of tight junction proteins mucin claudin-1, occludin, and ZO-1.

[0068] Immunofluorescence was used to measure the expression of claudin-1, occludin, and ZO-1 in the ileal epithelial tissues of mice in each group. As Figure 6 shown, the expression of claudin-1 in the ileum tissues of the H group of mice was significantly lower than that of the N group. However, after the intervention of H-AL4510, the expression level of claudin-1 increased significantly. The changing trends of the expression levels of occludin and ZO-1 in the epithelial tissues of each mouse were consistent with that of claudin-1, and their expression levels were significantly decreased in the hypobaric hypoxia environment compared with the N group. However, the intervention with L. plantarum AL4510 significantly increased the expression levels of occludin and ZO-1 in the ileum tissues of the H-AL4510 group of mice.

[0069] (VI) Intervention with L. plantarum AL4510 reduces the expression of inflammatory factors in the colon tissues of colitis mice

[0070] The levels of IL-6, IL-1β, and TNF-α in the ileum tissues were measured according to the instructions of the ELISA kit (purchased from Shanghai Enzyme-linked Biotechnology Co., Ltd.)

[0071] The results were as Figure 7As shown, the contents of IL-6, IL-1β, and TNF-α in the ileum tissue of mice in the low-pressure and hypoxic environment were significantly increased. However, the intervention of L. plantarum AL4510 significantly reduced the contents of IL-6, IL-1β, and TNF-α in the H-AL4510 group. This indicates that L. plantarum AL4510 can effectively alleviate the inflammatory response induced by the low-pressure and hypoxic environment.

[0072] (VII) Intervention of L. plantarum AL4510 increases the content of SCFAs in the intestinal contents of mice under hypobaric hypoxia

[0073] After thawing the collected mouse colon contents on ice, weigh 20 mg and put it into a 2 mL centrifuge tube. Add a small steel bead, add 1 mL of 0.5 M phosphoric acid solution (v / v), grind it with a cryogenic grinder at 30 Hz for 60 s, vortex it at 2500 rpm / min for 10 min, sonicate it at 4°C for 5 min, and then centrifuge it at 12000 rpm / min at 4°C for 10 min. Transfer 100 μL of the supernatant to a 1.5 mL centrifuge tube, mix it with 500 μL of MTBE extractant containing internal standard, vortex it at 2500 rpm / min for 3 min, sonicate it at 4°C for 5 min, and then centrifuge it at 12000 rpm / min at 4°C for 10 min. Transfer 200 μL of the supernatant to the liner of the injection vial and analyze it by GC-MS / MS. The main conditions of GC-MS / MS include: chromatographic column DB-FFAP, carrier gas is helium, column flow rate is 1.2 mL / min, inlet temperature is 250°C, injection volume is 1 μL. Set the temperature programming as follows: initial temperature 100°C is held for 5 min, and then heated to 150°C at a rate of 10°C / min and held for 3 min. Ion source temperature: 230°C, quadrupole temperature: 150°C.

[0074] SCFAs are the end products of the fermentation of dietary fiber by beneficial gut bacteria. They can protect the intestinal mucosa, maintain the integrity of the intestinal barrier, promote the absorption of nutrients, regulate the immune response, inhibit intestinal inflammation, and changes in the gut microbiota will affect the levels of SCFAs in the intestine. The levels of SCFAs in the intestinal contents of various mice were measured. As Figure 8 can be seen, compared with the N group, the contents of acetic acid, propionic acid, and butyric acid in the H group were significantly decreased in the simulated low-pressure and hypoxic environment. However, after the intervention of L. plantarum AL4510, the contents of acetic acid, propionic acid, and butyric acid in the intestinal contents of the H-AL4510 group of mice were significantly increased compared with the H group.

[0075] (VIII) L. plantarum AL4510 regulates the intestinal microbiota disorder induced by high-altitude hypoxia stress

[0076] 16S rRNA sequencing was performed on the colonic contents of each group of mice, and the sequencing results were analyzed.

[0077] High-altitude hypoxic environmental stress can damage the intestinal mucosal barrier function, promote the accumulation of anaerobic metabolism by-products, and then disrupt the intestinal flora homeostasis, resulting in a decrease in beneficial bacteria and an increase in harmful bacteria, thus exacerbating the intestinal microecological imbalance. Figure 9 As can be seen, compared with the N group, the Shannon index and Simpson index of the H group were both significantly increased, indicating that the Alpha diversity of microorganisms in this group was significantly increased and the richness of intestinal microorganisms changed significantly.

[0078] As Figure 10 can be seen, there was a significant difference in the intestinal microbial community distribution between the model group of mice induced by low pressure and hypoxia and normal mice. After intervention with L. plantarum AL4510, the intestinal microbial community of the H-AL4510 group of mice was also significantly separated compared with the H group. This shows that the intervention of L. plantarum AL4510 can change the intestinal flora structure.

[0079] As Figure 11 can be seen, compared with the N group, the abundances of Bacteroidota, Firmicutes, and Chlamydiae in the H group under low-pressure hypoxia increased, while the abundances of Verrucomicrobiota, Campylobacterota, and Desulfobacterota decreased. Figure 12 As can be seen, compared with the N group, the abundances of beneficial bacteria such as Akkermansi and Lactobacillus in the intestinal microorganisms of the H group of mice were significantly decreased; the genera Adlercreutzia, Chlamydia, and Alistipes were significantly enriched, indicating that the low-pressure hypoxia environment can increase the abundance of conditional pathogenic bacteria in the intestinal microorganisms of mice; compared with the H group, the intervention of L. plantarum AL4510 can significantly enrich Akkermansi in the healthy mice of the H-AL4510 group (p<0.05).

[0080] As can be seen from the above examples and test examples, Lactobacillus plantarum AL4510 provided by the present invention can effectively reduce the increase in pulmonary artery pressure and oxidative stress response induced by the low-pressure and hypoxic environment, thereby reducing ileal tissue inflammation, goblet cell loss and villus reduction, enhancing the expression of claudin-1, occludin and ZO-1 in the ileal epithelium, reducing intestinal injury in low-pressure and hypoxic mice, and protecting their intestinal barrier. L. plantarum AL4510 regulates the structure of the intestinal microbiota in low-pressure and hypoxic mice and increases the content of its metabolite SCFAs by reducing the abundances of potentially harmful bacteria (Chlamydia, Alistipes) and increasing the abundances of beneficial bacteria (Akkermansi and Lactobacillus) in the intestines of low-pressure and hypoxic mice, so as to slow down intestinal injury and the level of inflammation and promote intestinal barrier function.

[0081] The above are only the preferred embodiments of the present invention. It should be noted that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A strain of Lactobacillus plantarum AL4510, which is deposited in the China Center for Type Culture Collection, with the deposit address being Wuhan University, Wuhan, China, the deposit date being March 10, 2025, and the deposit number being CCTCC NO: M 2025421.

2. A microbial inoculum with the Lactobacillus plantarum AL4510 described in claim 1 as the main active ingredient.

3. The microbial inoculant according to claim 2, wherein The bacterial concentration of Lactobacillus plantarum AL4510 in the microbial inoculum is (0.5-2)×10 9 CFU / mL.

4. Use of the Lactobacillus plantarum AL4510 described in claim 1 or the microbial inoculum described in claim 2 or 3 in the preparation of a drug for relieving altitude sickness and / or intestinal injury.

5. The application according to claim 4, characterized in that, The altitude sickness and / or intestinal injury are both induced by simulating a low-pressure and low-oxygen environment at an altitude of 5000 m in a low-pressure oxygen chamber; The air pressure of the low pressure is: 50 - 54 kPa; The oxygen content of the low oxygen is: 11.0 - 11.5%.

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