Compound probiotics for relieving acute lung injury and application thereof

Abstract

The invention provides a compound probiotic for relieving acute lung injury and application of the compound probiotic, and particularly discloses application of the compound probiotic consisting of bifidobacterium animalis YRK-12 and lactobacillus rhamnosus LRa-Y8 in preparation of a medicine for relieving the acute lung injury. Wherein the preservation number of the bifidobacterium animalis YRK-12 is CGMCC (China General Microbiological Culture Collection Center) No.28597; the preservation number of the lactobacillus rhamnosus LRa-Y8 is CGMCC (China General Microbiological Culture Collection Center) No. 34186. Experimental verification shows that the compound probiotics can remarkably relieve acute lung injury induced by lipopolysaccharide (LPS) through a synergistic effect; specifically, the weight loss rate of mice is reduced, pathological injuries of lung tissues are improved (the structural integrity of alveolar alveoli is maintained, and inflammatory cell infiltration is reduced), the levels of proinflammatory factors (IL-1beta, TNF-alpha and IL-6) in serum and lung tissues are reduced, and the level of anti-inflammatory factors (IL-4) is increased, so that the immune balance of the lung is regulated through an intestine-lung axis; and a safe and effective novel micro-ecological regulation strategy is provided for prevention and treatment of acute lung injury.

Description

Technical Field

[0001] The present invention belongs to the field of microbial technology, and particularly relates to a composite probiotic for alleviating acute lung injury and an application thereof. Background Art

[0002] Acute lung injury (ALI) is a common, critical respiratory illness with an abrupt onset and rapid progression, primarily manifested by progressive hypoxic respiratory failure. It is essentially a milder form of acute respiratory distress syndrome (ARDS). Epidemiological studies have shown that the incidence of ALI / ARDS is as high as 57-78 cases per 100,000 people annually, with a mortality rate ranging from 35% to 46%. This not only severely threatens patients' lives and compromises their quality of life, but also places a heavy burden on families and society. Without timely and effective intervention, ALI can rapidly progress to ARDS and even lead to death.

[0003] The core pathogenesis of this disease lies in an uncontrolled inflammatory response. During the pathological process, the massive release of proinflammatory mediators triggers an inflammatory cascade, leading to damage to pulmonary capillary endothelial cells and alveolar epithelial cells. Characteristic pathological changes include abnormally increased pulmonary microvascular permeability, leading to pulmonary edema, hyaline membrane formation, and later pulmonary fibrosis. Essentially, the imbalance of inflammation in the lungs leads to the destruction of the pulmonary vascular endothelial barrier and the alveolar epithelial barrier, ultimately causing acute respiratory dysfunction.

[0004] Given the central role of inflammation in the development of ALI / ARDS, targeted inhibition of the inflammatory cascade has become a highly promising preventive and therapeutic strategy. Gram-negative bacterial infection is a common trigger of inflammation. Its outer membrane lipopolysaccharide (LPS), a key endotoxin component, potently induces excessive secretion of proinflammatory mediators, driving uncontrolled expansion of inflammation in the lungs. LPS-induced animal or cell models closely mimic the pathological damage and temporal course of ALI and are widely used in preclinical screening of ALI preventive and therapeutic drugs.

[0005] Current clinical treatments primarily rely on mechanical ventilation and pharmacological interventions (such as glucocorticoids and inhaled nitric oxide), but these have significant limitations: mechanical ventilation can easily lead to secondary injuries such as barotrauma; traditional medications are subject to side effects (such as immunosuppression caused by steroids) and drug resistance; and there is no specific treatment that is both highly effective and safe. Recent studies have demonstrated that the gut microbiome is deeply involved in pulmonary immune regulation through the "gut-lung axis." Specific probiotic strains have shown potential for anti-inflammatory and barrier repair, but the efficacy of single strains is limited, and the mechanisms of synergistic intervention with combined probiotics for ALI remain unclear. Summary of the Invention

[0006] In response to the problems existing in the prior art, the purpose of the present invention is to provide a composite probiotic for alleviating acute lung injury and its application. It is found for the first time that the combination of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8 shows a clear synergistic effect in reducing weight loss rate, improving lung pathological damage, regulating the balance of inflammatory factors, etc., which solves the problem of limited efficacy of a single probiotic.

[0007] The purpose of the present invention is achieved through the following technical solutions: The present invention provides a use of a composite probiotic in preparing a medicine for alleviating acute lung injury, wherein the composite probiotic consists of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8; Bifidobacterium animalis YRK-12 is deposited in the General Microbiology Center of China Microbial Culture Management Committee and is classified as Bifidobacterium animalis Bifidobacterium animalis , the deposit number is CGMCC NO.28597, and the deposit date is October 9, 2023; Lactobacillus rhamnosus LRa-Y8 was deposited in the General Microbiology Center of China National Microbiological Culture Management Committee and was classified as Lactobacillus rhamnosus Lacticaseibacillus rhamnosus The deposit number is CGMCC NO.34186, and the deposit date is April 14, 2025.

[0008] Furthermore, the ratio of the live bacteria content of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8 in the composite probiotics is 1:5 to 5:1.

[0009] Furthermore, the effective viable count of the composite probiotics in the drug is not less than 1×10 10 CFU / mL.

[0010] Furthermore, the acute lung injury is induced by lipopolysaccharide.

[0011] Furthermore, the dosage form of the drug is an oral preparation, including tablets, capsules, granules or suspensions.

[0012] Furthermore, the drug can reduce the weight loss rate caused by acute lung injury, improve lung tissue pathological damage, and regulate the levels of inflammatory factors in serum and lung tissue.

[0013] Furthermore, the improvement of lung tissue pathological damage includes: maintaining the integrity of alveolar structure, reducing alveolar septal thickening and fusion, and reducing inflammatory cell infiltration and interstitial edema.

[0014] Furthermore, the regulation of inflammatory factor levels in serum and lung tissue includes: downregulating the expression of pro-inflammatory factors IL-1β, TNF-α, and IL-6, and upregulating the expression of anti-inflammatory factor IL-4.

[0015] Culture deposit information: The animal Bifidobacterium was named YRK-12, which was deposited in the General Microbiology Center of China Microbiological Culture Management Committee (CGMCC), address: No. 3, Yard 1, Beichen West Road, Chaoyang District, Beijing; Bifidobacterium animalis , the deposit number is CGMCC NO.28597, and the deposit date is October 9, 2023.

[0016] Lactobacillus rhamnosus LRa-Y8, the strain is deposited in the General Microbiology Center of China Microbiological Culture Management Committee (CGMCC), address: No. 3, No. 1 Beichen West Road, Chaoyang District, Beijing; the classification name is Lactobacillus rhamnosus Lacticaseibacillus rhamnosus The deposit number is CGMCC NO.34186, and the deposit date is April 14, 2025.

[0017] The composite probiotics provided by the present invention have the following significant beneficial effects in alleviating acute lung injury: 1. Significant synergistic effect: Experimental results show that the relief effect of the combination of two strains is significantly better than that of a single strain (YRK-12 or LRa-Y8) and other combination combinations (such as YRK-12+BB12+LRa-Y8). It shows a clear synergistic effect in reducing weight loss rate, improving lung pathological damage, and regulating the balance of inflammatory factors, solving the problem of limited efficacy of single probiotics.

[0018] 2. Multi-target relief of lung injury: By targeting and regulating the "gut-lung axis", this compound probiotic can alleviate acute lung injury from multiple levels: Metabolic level: significantly reverses LPS-induced rapid weight loss and maintains metabolic homeostasis; Histopathological level: effectively protects the integrity of alveolar structure, reduces alveolar septum thickening, inflammatory cell infiltration and interstitial edema, and inhibits hyaline membrane formation; Immune regulation: significantly downregulates the levels of pro-inflammatory factors (IL-1β, TNF-α, IL-6) in serum and lung tissue, while upregulating the levels of anti-inflammatory factors (IL-4), rebuilding the immune balance of the lungs and blocking the inflammatory cascade amplification effect.

[0019] 3. High safety and no significant side effects: The strains used are probiotics derived from the human intestine (YRK-12) or commercially safe strains (LRa-Y8), which can be effective through oral administration, avoiding the immunosuppressive side effects of traditional drugs (such as glucocorticoids) and the risk of secondary injury from mechanical ventilation, and are suitable for long-term or early intervention.

[0020] 4. Providing a novel microecological strategy for acute lung injury: This invention clarifies for the first time the synergistic mechanism of YRK-12 and LRa-Y8, breaking through the efficacy bottleneck of existing acute lung injury treatments and providing a safe and efficient new microecological regulation solution for the clinical prevention and treatment of acute lung injury / acute respiratory distress syndrome (ALI / ARDS), which has important clinical translational value. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] The present invention will be further described below with reference to the accompanying drawings and examples: Figure 1 Shows the effects of different probiotics / compound probiotics on body weight in mice with acute lung injury induced by LPS; Figure 2 Shown are the effects of different probiotics / compound probiotics on lung pathology in mice with acute lung injury induced by LPS; (A) is the lung tissue pathological morphology; (B) is the HE score; Figure 3 The effects of different probiotics / compound probiotics on serum inflammatory factors in mice with acute lung injury induced by LPS are shown; (A) the level of inflammatory factor IL-1β; (B) the level of inflammatory factor IL-4; Figure 4 The effects of different probiotics / compound probiotics on inflammatory factors in lung tissue of mice with acute lung injury induced by LPS are shown; among them, (A) the level of inflammatory factor IL-1β; (B) the level of inflammatory factor IL-6; (C) the level of inflammatory factor TNF-α. DETAILED DESCRIPTION

[0022] The examples are provided to better illustrate the present invention, but are not intended to limit the present invention to the examples. Therefore, non-essential improvements and adjustments to the embodiments made by those skilled in the art based on the above-mentioned invention still fall within the scope of protection of the present invention.

[0023] The endpoints of the ranges and any values ​​disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoints of each range, the endpoints of each range and 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 considered to be specifically disclosed herein.

[0024] The present invention will be described in detail below through examples. It should be understood that the following examples are only used to further explain and illustrate the content of the present invention in detail, and are not intended to limit the present invention.

[0025] In the following examples, LPS was purchased from Beijing Solaibao Technology Co., Ltd., L8880. Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8 were provided by Shaanxi Yiruikang Biotechnology Co., Ltd., and the strains are deposited with the General Microbiology Center of the China Culture Collection Administration. The strains are derived from the human intestine. The BB-12 strain was obtained from Chr. Hansen, Denmark. Mice / Diet / Bedding: Diet was purchased from Beijing Huafukang Biotechnology Co., Ltd.

[0026] The modified MRS medium formula is as follows: peptone 10 g, yeast extract 5 g, glucose 20 g, beef extract 10 g, K2HPO4 2 g, diammonium citrate 2 g, MgSO4·7H2O 0.58 g, MnSO4·4H2O 0.25 g, anhydrous sodium acetate 5 g, Tween 80 1 mL, cysteine ​​hydrochloride 0.5 g, distilled water to 1 L, pH to 6.5, 121 o C sterilize for 15 min.

[0027] Example 1: Microbial culture preparation (1) Preparation of Bifidobacterium animalis YRK-12 A probiotic strain was obtained by isolating human intestinal flora and was identified as Bifidobacterium animalis Bifidobacterium animalis , named it Bifidobacterium animalis YRK-12. The strain is deposited in the General Microbiology Center of China Microorganism Culture Management Committee with the deposit number CGMCC NO.28597 and the deposit date of October 9, 2023.

[0028] The isolated animal Bifidobacterium YRK-12 was subcultured twice in the modified MRS liquid medium, and then inoculated into the modified MRS liquid medium at a 10% inoculum volume. o C and 0% oxygen for 24 h. Centrifuge (4000 rpm, 10 min) and remove the supernatant. Wash the cells twice with PBS and resuspend them in 0.9% saline for gavage to adjust the concentration to 1 × 10 10 CFU / mL.

[0029] (2) Preparation of Bifidobacterium animalis BB12 After Bifidobacterium animalis BB-12 was subcultured twice in the modified MRS liquid medium, it was inoculated into the modified MRS liquid medium at a 10% inoculum volume and incubated at 37 ± 1 o C and 0% oxygen for 24 h. The supernatant was removed by centrifugation (4000 rpm, 10 min), and the cells were washed twice with PBS. When gavage was performed, the cells were resuspended in 0.9% saline and the concentration of the bacterial suspension was adjusted to 1 × 10 10 CFU / mL.

[0030] (3) Preparation of Lactobacillus rhamnosus LRa-Y8 Lactobacillus rhamnosus LRa-Y8 was deposited in the General Microbiology Center of China National Microbiological Culture Management Committee with the deposit number CGMCC NO.34186 and the deposit date of April 14, 2025.

[0031] After Lactobacillus rhamnosus LRa-Y8 was subcultured twice in the modified MRS liquid medium, it was inoculated into the modified MRS liquid medium at a 10% inoculum volume and incubated at 37 ± 1 o C and 0% oxygen for 24 h. The supernatant was removed by centrifugation (4000 rpm, 10 min), and the cells were washed twice with PBS. When gavage was performed, the cells were resuspended in 0.9% saline and the concentration of the bacterial suspension was adjusted to 1 × 10 10 CFU / mL.

[0032] Example 2 This embodiment provides a composite probiotic for alleviating acute lung injury, wherein the composite probiotic consists of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8.

[0033] The preparation method of the composite probiotics comprises: mixing the bacterial suspensions of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8 prepared in Example 1 in a ratio of 1:1, and adjusting the total bacterial concentration of the two bacteria in the bacterial agent to 1×10 10 CFU / mL.

[0034] Test case: Effects of compound probiotics on acute lung injury To explore the effects of different combinations of compound probiotics on acute lung injury, the following animal experiments were conducted in this test case: Forty-eight 8-week-old male C57BL / 6J mice (purchased from Beijing Huafukang Biotechnology Co., Ltd.) were randomly divided into 8 groups after one week of adaptive feeding: blank control group, LPS treatment group, LPS + Bifidobacterium animalis YRK-12 intervention group, LPS + Bifidobacterium animalis BB12 intervention group, LPS + Lactobacillus rhamnosus LRa-Y8 intervention group, LPS + Bifidobacterium animalis YRK-12 + Lactobacillus rhamnosus LRa-Y8 intervention group, LPS + Bifidobacterium animalis BB12 + Lactobacillus rhamnosus LRa-Y8 intervention group, and LPS + Bifidobacterium animalis YRK-12 + Bifidobacterium animalis BB12 + Lactobacillus rhamnosus LRa-Y8 intervention group. The compound probiotic groups were gavaged for 28 consecutive days, with the same gavage amount of bacteria being 1×10 10 CFU were measured using a 100 μL gavage volume. Mice in the blank control and LPS-treated groups were gavaged with the same volume of normal saline. The mice were maintained under a 12-h light / dark cycle and had free access to water and food.

[0035] 1. Weight change rate The weight of mice in each group was recorded before modeling and before sacrifice, and the weight loss ratio of mice was calculated as follows: weight change ratio = (weight before sacrifice - weight before modeling) / weight before modeling. The weight of mice changed significantly after modeling.

[0036] 2. H&E staining Lung tissue samples were fixed in 4% neutral buffered formalin for 24 hours, dehydrated with graded ethanol (70% → 80% → 90% → 95% → 100%), and cleared with xylene. After paraffin embedding, 4-μm-thick sections were prepared. Sections were dewaxed in xylene and rehydrated with graded ethanol (100% → 95% → 85% → 70%). The sections were then stained with hematoxylin for 5 minutes and rinsed with running water. The sections were then differentiated with 1% hydrochloric acid and ethanol for 3 seconds to remove nonspecific staining. The sections were then blued with saturated lithium carbonate solution for 30 seconds to restore the blue color of the nuclei. The sections were counterstained with 0.5% eosin solution for 2 minutes. The sections were then dehydrated again with graded ethanol, cleared with xylene, and mounted with neutral gum. Lung tissue pathomorphological changes (such as inflammatory infiltration, alveolar structural destruction, and edema) were observed under a light microscope.

[0037] 3. Determination of serum inflammatory factors EnzymeCore Biotechnology Co., Ltd. (EnzymeCore Biotechnology) ELISA kit was used to detect serum IL-1β and IL-4 levels. The operation process was as follows: serum samples were 4 oC. Centrifuge at 3000×g for 10 minutes, remove the supernatant and dilute 10-fold; simultaneously use the standard diluent to prepare a 7-point concentration gradient standard curve from 7.8 to 500 pg / mL; add 100 μL of standard or diluted sample to the antibody pre-coated 96-well plate, and o C for 90 minutes; after washing, 100 μL / well biotinylated detection antibody (37 o C for 60 minutes), horseradish peroxidase-labeled streptavidin (37 o C incubate in the dark for 30 minutes) and TMB substrate solution (37 o C in the dark for 15 minutes), rinse with PBS three times between each step; finally, add 50 μL / well stop solution to terminate the reaction, and measure the OD value at 450 nm on a microplate reader within 10 minutes. All samples were set up in triplicate wells, and the standard curve fitting required R 2 ≥0.99, the concentration was calculated based on the mean of duplicate wells.

[0038] 4. Determination of tissue inflammatory factors The detection of inflammatory factors (TNF-α, IL-1β, and IL-6) in lung tissue was performed using an EnzymeCore ELISA kit. Fresh or frozen lung tissue (30 mg) was homogenized in PBS-Triton X-100 buffer containing protease inhibitors on ice for 4 h. o C. Centrifuge at 12,000 × g for 15 minutes and collect the supernatant. The total protein concentration of the tissue was determined by BCA assay (BSA standard curve 0–2000 μg / mL, R 2 ≥0.99). For ELISA testing, the tissue supernatant was diluted 1:5 according to the dilution factor determined in the pre-experiment and added to the pre-coated plate simultaneously with the 7.8–500 pg / mL standard. o C incubation, biotinylated antibody (60 minutes) and HRP-streptavidin (30 minutes) reaction, TMB color development in the dark for 15 minutes after termination, OD value was measured at 450 nm. The standard curve was fitted with four parameters (R 2 ≥0.99), the final concentration was calculated by the formula [ELISA concentration (pg / mL) × dilution factor] / [BCA protein concentration (μg / mL) × 1000] × 10 6 The protein content was converted to pg / mg to eliminate differences in tissue sampling.

[0039] Animal test results: (1) Effects of compound probiotics on body weight changes in mice Depend on Figure 1The results show that after intraperitoneal injection of LPS, the mice experienced a dramatic weight loss, with a weight loss rate of 17.13%. Following probiotic treatment, all treatment groups showed a reduction in weight loss, with the YRK-12 + LRa-Y8 group showing a more significant effect in alleviating weight loss, surpassing the YRK-12 and LRa-Y8 groups alone, demonstrating a synergistic effect.

[0040] Interestingly, the YRK-12+LRa-Y8+BB12 combination was less effective than the single-bacteria and dual-bacteria combinations in alleviating weight loss. The results suggest that the YRK-12+LRa-Y8 combination is the most effective in reversing LPS-induced weight loss and maintaining metabolic homeostasis.

[0041] (2) Effects of compound probiotics on lung tissue pathology in mice like Figure 2 As shown, the blank control group had intact and clear alveolar structure, uniform alveolar septa without thickening, tightly arranged bronchial epithelial cells, and no inflammatory cell infiltration, congestion, or edema, indicating normal lung tissue. Lung tissue in the LPS-treated group exhibited typical acute injury pathological changes: severe destruction of alveolar structure, diffuse thickening and fusion of alveolar septa; extensive capillary congestion, infiltration of large numbers of neutrophils and other immune cells; and localized alveolar collapse with hyaline membrane formation and interstitial edema.

[0042] Single bacteria intervention group: YRK-12 group: alveolar septal thickening was alleviated, and inflammatory cell infiltration decreased by about 30%, but local congestion lesions were still visible; BB12 group: Compared with the LPS group, the improvement was limited, the inflammatory exudate was reduced, and the alveolar fusion area was still significant; LRa-Y8 group: The degree of edema was alleviated, but neutrophil infiltration was still obvious.

[0043] Double bacteria combination group: BB12+LRa-Y8 group: Inflammatory cell infiltration decreased, alveolar structure partially recovered, and occasional septal thickening was observed; YRK-12+LRa-Y8 group: The synergistic protective effect was significant. Alveolar structure was essentially intact, with minimal septal thickening and congestion. Inflammatory cell infiltration was reduced, and there was no hyaline membrane formation or interstitial edema.

[0044] It can be seen that the combination of YRK-12 and LRa-Y8 is significantly superior to single bacteria and other combination combinations in maintaining alveolar structural integrity and inhibiting inflammatory exudate. In addition, we found that the effect of the three-bacteria combination of YRK-12, BB12, and LRa-Y8 was not very significant.

[0045] (3) Effects of compound probiotics on serum inflammatory factors in mice like Figure 3As shown, the level of pro-inflammatory factor IL-1β in the LPS model group was significantly increased, reflecting a strong inflammatory response. IL-1β in the single bacteria group was partially reduced. IL-1β in the YRK-12+LRa-Y8 dual bacteria complex group was significantly reduced, showing a synergistic anti-inflammatory effect; BB12+LRa-Y8 was also significantly reduced, but weaker than the YRK-12+LRa-Y8 group. For the anti-inflammatory factor IL-4: The IL-4 level in the LPS model group was significantly suppressed, indicating an imbalance in immune regulation. IL-4 in the single bacteria group increased slightly. IL-4 in the YRK-12+LRa-Y8 group increased significantly, close to the blank group ( P <0.05); IL-4 in the BB12+LRa-Y8 group was significantly higher than that in the LPS group, but significantly lower than that in the YRK-12+LRa-Y8 group ( P <0.05). In addition, the YRK-12+BB12+LRa-Y8 combination group had an inhibitory effect on serum proinflammatory factors, which was better than the BB12 and LRa-Y8 single bacteria group, as well as the BB12+LRa-Y8 group, but not as good as the YRK-12 single bacteria group and the YRK-12+LRa-Y8 combination group.

[0046] The results showed that the combination of YRK-12+LRa-Y8 can synergistically inhibit pro-inflammatory factors and activate anti-inflammatory factors, rebuild immune balance, and exhibit the best anti-inflammatory effect.

[0047] (4) Effects of compound probiotics on inflammatory factors in mouse lung tissue The levels of inflammatory factors (TNF-α, IL-1β, IL-6) in lung tissue were further detected. Figure 4 As shown, TNF-α, IL-1β, and IL-6 levels in the model mice were significantly elevated compared to the blank control group, indicating an acute inflammatory response consistent with the core pathological features of acute lung injury. The YRK-12 + LRa-Y8 group demonstrated the strongest synergistic inhibitory effect in suppressing inflammation, demonstrating superior inhibitory effects on TNF-α, IL-1β, and IL-6 compared to either YRK-12 or LRa-Y8 alone, and also surpassing the combined effects of BB12 and LRa-Y8. Similarly, the YRK-12 + BB12 + LRa-Y8 tri-bacterial combination group did not demonstrate a stronger synergistic effect. This suggests that the combination of YRK-12 and LRa-Y8 significantly outperforms single bacteria or BB12 + LRa-Y8 alone in modulating the gut-lung axis and repairing the lung barrier by synergistically downregulating core pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in lung tissue, thereby blocking the inflammatory cascade. This demonstrates a unique synergistic mechanism between the two bacteria in regulating the gut-lung axis and repairing the lung barrier.

[0048] Finally, it should be noted that the above is only used to illustrate the technical solution of the present invention and is not limiting. Although the present invention is described in detail with reference to the preferred arrangement scheme, ordinary technicians in this field should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the spirit and scope of the technical solution of the present invention.

Claims

1. Use of a composite probiotic in preparing a medicine for alleviating acute lung injury, characterized in that: The composite probiotics consist of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8; Bifidobacterium animalis YRK-12 is deposited in the General Microbiology Center of China Microbial Culture Management Committee and is classified as Bifidobacterium animalis Bifidobacterium animalis , the deposit number is CGMCC NO.28597, and the deposit date is October 9, 2023; Lactobacillus rhamnosus LRa-Y8 was deposited in the General Microbiology Center of China National Microbiological Culture Management Committee and was classified as Lactobacillus rhamnosus Lacticaseibacillus rhamnosus The deposit number is CGMCC NO.34186, and the deposit date is April 14, 2025.

2. The use according to claim 1, characterized in that The ratio of the live bacteria content of Bifidobacterium animalis YRK-12 and Lactobacillus rhamnosus LRa-Y8 in the composite probiotics is 1:5 to 5:

1.

3. The use according to claim 1, characterized in that The effective viable bacteria count of the composite probiotics in the drug is not less than 1×10 10 CFU / mL.

4. The use according to claim 1, characterized in that The acute lung injury was induced by lipopolysaccharide.

5. The use according to claim 1, characterized in that The dosage form of the drug is an oral preparation, including tablets, capsules, granules or suspensions.

6. The use according to claim 1, characterized in that The drug can reduce the weight loss rate caused by acute lung injury, improve lung tissue pathological damage, and regulate the levels of inflammatory factors in serum and lung tissue.

7. The use according to claim 6, characterized in that The improvement of lung tissue pathological damage includes: maintaining the integrity of alveolar structure, reducing alveolar septum thickening and fusion, and reducing inflammatory cell infiltration and interstitial edema.

8. The use according to claim 6, characterized in that The regulation of inflammatory factor levels in serum and lung tissue includes: downregulating the expression of pro-inflammatory factors IL-1β, TNF-α, and IL-6, and upregulating the expression of anti-inflammatory factor IL-4.

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