Rumen ball strain and application thereof

Abstract

The invention discloses a rumen ball strain and application thereof, belongs to the technical field of biology, and aims to solve the problems of side effects of antibiotic treatment, limitation of total fecal fungus transplantation and the limitation of insufficiency of probiotics in treatment of sepsis-related lung injury in the existing detection technology. The invention provides a ruminococcus sp. Strain Rum-307, which is separated from excrement of healthy people, has a unique gene sequence, and can be rapidly colonized after antibiotic treatment, reduce intestinal permeability and prevent endotoxin transfer; by regulating CD4 + T cell subtypes, the level of proinflammatory factors (TNF-alpha and IL-6) is reduced, the anti-inflammatory factor (IL-10) is improved, and immune balance is achieved. In a CLP sepsis model, the Rum-307 can significantly improve the wet / dry ratio, the pathological score and the survival rate of the lung. The strain Rum 307 can be prepared into capsules, oral liquid and other dosage forms, is easy to produce, is suitable for treating sepsis, acute respiratory distress syndrome, intestinal sepsis and other diseases, and has remarkable clinical and commercial prospects.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of biotechnology, and particularly relates to a strain of rumenococcus and application thereof. BACKGROUND

[0002] Sepsis is a systemic inflammatory response syndrome triggered by severe infection, often leading to multiple organ failure, among which acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is one of the main complications, with high morbidity and mortality. The pathogenesis of sepsis is complex, involving excessive activation of the immune system, excessive release of pro-inflammatory factors (TNF-α, IL-6), and impaired intestinal barrier function. In recent years, studies have shown that intestinal dysbiosis plays a key role in the occurrence and development of sepsis. Intestinal barrier disruption leads to the entry of bacteria and their metabolites (endotoxins) into the blood, exacerbating systemic inflammatory response and further worsening lung injury. The study of the intestinal-lung axis further reveals that the intestinal flora affects lung inflammatory response through metabolic products (short-chain fatty acids, SCFAs) and immune regulation (CD4+ T cell subtype differentiation), providing a new theoretical basis for the treatment of sepsis.

[0003] In the prior art, the treatment of sepsis mainly relies on antibiotics, anti-inflammatory drugs and supportive treatment, such as fluid resuscitation and mechanical ventilation. In addition, fecal microbiota transplantation (FMT) and probiotic therapy as means to restore intestinal flora have shown certain efficacy in some diseases (such as Clostridium difficile infection). However, the prior art has the following significant shortcomings in dealing with sepsis-related lung injury:

[0004] 1. Significant side effects of antibiotic treatment

[0005] Antibiotics are the cornerstone of sepsis treatment, but broad-spectrum antibiotics, while killing pathogenic bacteria, severely disrupt the intestinal beneficial flora, leading to dysbiosis, reducing the production of short-chain fatty acids, weakening the expression of tight junction proteins (ZO-1, occludin) of intestinal epithelial cells, increasing intestinal permeability, and allowing harmful substances such as endotoxins to leak into the blood, exacerbating systemic inflammation and lung injury.

[0006] 2. Limitations of fecal microbiota transplantation

[0007] Fecal microbiota transplantation uses healthy donor fecal flora, which contains a variety of bacteria, fungi and other microorganisms, with complex and unclear composition, and may introduce potential pathogenic bacteria, increasing the risk of infection, especially for sepsis patients with low immune function; the donor fecal flora varies due to individual differences, making it difficult to standardize the treatment effect, limiting its widespread application in clinical practice; fecal microbiota transplantation cannot precisely intervene in the specific pathogenesis of sepsis lung injury (intestinal-lung axis regulation or immune imbalance), and has limited efficacy.

[0008] 3. Deficiency of existing probiotics

[0009] Existing probiotics (lactic acid bacteria, bifidobacteria) are mainly used for general intestinal health maintenance and are difficult to effectively colonize in the environment of severe dysbiosis after antibiotic treatment, limiting their application in critical conditions such as sepsis; current probiotic research is mostly focused on improving mild intestinal problems, lacking specific mechanisms for sepsis lung injury, such as reducing lung pro-inflammatory factor levels or repairing severely damaged intestinal barrier through the intestinal-lung axis; existing probiotic research is mostly based on healthy animal models or simple dysbiosis models, which fail to fully simulate the complex pathological environment of sepsis patients receiving large doses of antibiotic treatment, and have limited clinical translation value.

[0010] Although the intestinal-lung axis has attracted much attention in sepsis research, existing technologies lack precise means to regulate lung inflammation through intestinal flora, especially after antibiotics destroy the flora, and no probiotic has been proven to effectively reduce lung inflammatory factors (TNF-alpha, IL-6) and improve lung injury in sepsis models. SUMMARY

[0011] Based on the literature research and research inspiration of the side effects of antibiotic treatment, the limitations of full fecal flora transplantation, and the deficiencies of probiotics in the treatment of sepsis-related lung injury in the prior art, the present application provides a Ruminococcus sp. strain Rum-307 and its application, which repairs the intestinal barrier, regulates the immune response, and improves sepsis-related lung injury through the intestinal-lung axis mechanism through precise targeted intestinal flora transplantation.

[0012] The present application significantly improves sepsis-related lung injury through precise targeted intestinal flora transplantation. Rum-307 can rapidly colonize in the intestinal environment after antibiotic destruction, produce short-chain fatty acids, enhance the expression of tight junction proteins in intestinal epithelial cells, reduce intestinal permeability, and prevent endotoxins from entering the blood; by regulating CD4+ T cell subtypes (Treg, Th1, Th17), reducing pro-inflammatory factor (TNF-alpha, IL-6) levels, and increasing anti-inflammatory factor (IL-10), immune balance is achieved; through the intestinal-lung axis mechanism, lung inflammation is reduced, and lung wet / dry ratio and pathological score are improved. Rum-307 can be formulated into capsules, oral solutions, etc., which are easy to produce and clinically applicable. In the CLP sepsis model, Rum-307 significantly improves the survival rate of mice, showing therapeutic potential and can be extended to ARDS, bacterial pneumonia, and other diseases. The present application overcomes the limitations of antibiotic side effects and full fecal flora transplantation, providing a safe and precise adjuvant therapy for critically ill patients, and has broad clinical and commercial prospects.

[0013] In a first aspect, the present application provides a Ruminococcus sp. strain, which is Rum-307, and the preservation number is CGMCC No. 46385, the preservation date is February 17, 2025, and the preservation unit is China General Microbiological Culture Collection Center, and the classification name is Ruminococcus sp.

[0014] In a second aspect, a probiotic agent comprises the Ruminococcus sp. strain of claim 1.

[0015] In a third aspect, the present application further provides the use of the Ruminococcus sp. strain or the probiotic agent of claim 2 in the preparation of a drug for alleviating or treating sepsis-related lung injury.

[0016] In a fourth aspect, the present application further provides the use of the probiotic agent in the preparation of a drug for alleviating or treating acute respiratory distress syndrome.

[0017] In a fifth aspect, the present application further provides the use of the probiotic agent in the preparation of a drug for alleviating or treating enterogenic sepsis.

[0018] In a sixth aspect, the present application further provides the use of the probiotic agent in the preparation of a drug for alleviating or treating multiple organ dysfunction syndrome.

[0019] Compared with the prior art, the present application has the following advantages:

[0020] 1. Significantly improve lung injury and provide a safe and efficient treatment regimen: Compared with antibiotic treatment and whole fecal flora transplantation, the Ruminococcus sp. strain Rum-307 of the present application significantly improves lung injury in a cecal ligation and puncture (CLP) sepsis model, showing reduced lung inflammatory cell infiltration, reduced lung wet / dry ratio, and improved alveolar structure integrity. Rum-307 effectively suppresses systemic inflammatory response syndrome by inhibiting the expression of pro-inflammatory factors (TNF-α, IL-6), which is superior to ordinary probiotics which are limited to intestinal function regulation. It is strictly screened, has high safety, has no risk of infection, and is suitable for critically ill patients with low immune function. Compared with the complexity of the components of whole fecal flora transplantation and the risk of potential pathogenic bacteria, Rum-307 uses a single strain, the efficacy is controllable, and the antibiotic resistance property makes it still active after large-dose antibiotic treatment, providing a safe and efficient adjuvant treatment regimen for sepsis patients.

[0021] 2. Rapid colonization and bidirectional immune regulation, overcoming the limitations of antibiotic-induced disruption of intestinal flora: Rum-307 rapidly colonizes in a severe dysbiosis environment, restores the microecological balance, repairs the intestinal barrier, reduces permeability, prevents endotoxins from entering the blood, and indirectly relieves lung damage. Compared to ordinary probiotics, which are insufficient in colonization after antibiotics, Rum-307 not only enhances the expression of tight junction proteins, but also regulates CD4+ T cell subtypes (Treg, Th1, Th17) - upregulates anti-inflammatory factors (IL-10), downregulates pro-inflammatory factors (TNF-α, IL-6), achieves immune balance, and reduces lung inflammation through the gut-lung axis mechanism, which is superior to the unstable efficacy of whole fecal flora transplantation and the lack of specific mechanisms of existing probiotics, providing comprehensive protection for sepsis treatment.

[0022] 3. High efficiency of production and potential for wide clinical application: Rum-307 strain is easy to scale up, store and transport, has strong stability, can be prepared into capsules, oral solutions or freeze-dried powders, etc. It meets the existing industrialized production standards of probiotics, has low production cost, is easy to promote clinically, and overcomes the limitations of complex preparation of whole fecal flora transplantation and single function of ordinary probiotics. It is not only suitable for sepsis-related lung injury, but also can be extended to acute respiratory distress syndrome (ARDS), enterogenic sepsis and multiple organ dysfunction syndrome (MODS), meeting the high demand of ICU and postoperative rehabilitation scenes. Rum-307 is suitable for a variety of inflammatory diseases through the gut-lung axis and immune regulation mechanism, has significant clinical and commercial prospects, and is superior to the existing technology in application range and production efficiency, which can be quickly converted into marketable products. BRIEF DESCRIPTION OF DRAWINGS

[0023] Figure 1 Lung tissue image in the improvement of lung injury in sepsis mice by Rum-307.

[0024] Figure 2 H&E staining of lung tissue sections in the improvement of lung injury in sepsis mice by Rum-307.

[0025] Figure 3 ELISA detection of serum inflammatory factors.

[0026] Figure 4 Flow chart of Rum-307 colonization experiment.

[0027] Figure 5 Survival curve in the improvement of lung injury in sepsis mice by Rum-307.

[0028] Figure 6 Lung tissue image in the potential application of Rum-307 under simulated clinical conditions.

[0029] Figure 7 Figure 6 is a lung tissue section H&E staining chart for Rum-307 in potential application under simulated clinical conditions.

[0030] Figure 8 Figure 7 is a small intestine section H&E staining chart.

[0031] Figure 9 Figure 8 is a mouse abdominal wound healing degree chart.

[0032] Figure 10 Figure 9 is a survival curve chart of Rum-307 in relieving enterogenic sepsis.

[0033] Figure 11 Figure 10 is a spleen section H&E staining chart.

[0034] Figure 12 Figure 11 is a kidney section H&E staining chart.

[0035] Figure 13 Figure 12 is a liver section H&E staining chart.

[0036] Figure 14 Figure 13 is a survival curve chart of Rum-307 in relieving sepsis-related multiple organ dysfunction syndrome (MODS). DETAILED DESCRIPTION

[0037] In order to make the objects, technical solutions and advantages of the present application clearer, further detailed description will be given below in combination with examples and drawings. It should be understood that the specific examples described are only for explaining specific applications of the present application, and are not used to limit the scope of the present application. Through these examples, it is intended to help understand the principles, operating methods and superiorities of the present application, but does not exclude that proper adjustment and variation can be made in the implementation process of the present application.

[0038] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0039] Example 1: Improvement of rumenococcus on lung injury of sepsis mice

[0040] Experimental object: C57BL / 6 mice, 8 weeks old, male, body weight about 20-25 grams.

[0041] Rumenococcus strain: specific strain (number Rum-307) screened out, cultured in vitro and freeze-dried for preservation, bacterial liquid concentration 109CFU / mL.

[0042] CLP model: Cecal Ligation and Puncture (CLP) method was used to construct a mouse sepsis model.

[0043] Antibiotic treatment: A large dose of antibiotic mixture (azithromycin, neomycin, ciprofloxacin, miconazole, once a day, continuous gavage for 5 days, 50 mg / kg) was given.

[0044] In the above experiment, the strain of Ruminococcus Rum-307 was screened from fresh fecal samples of healthy volunteers. The specific method is as follows: healthy adult volunteers with no history of antibiotic use for at least three months and normal intestinal function were selected, and their fresh fecal samples were collected and sent to the laboratory within 2 hours. Enrichment culture was carried out under anaerobic conditions using modified GAM medium (Gifu Anaerobic Medium), followed by dilution plating on RCM (Reinforced Clostridial Medium) solid medium for anaerobic culture (37°C, 48 hours). Single colonies with stable morphology and consistent colony characteristics were selected for 16S rRNA sequencing and preliminary identification, and further confirmed by comparing the NCBI database to be of the genus Ruminococcus. After multiple rounds of isolation, rescreening and drug resistance testing, a specific strain with strong antibiotic post-colonization ability and immune regulation potential was obtained.

[0045] Experimental grouping:

[0046] Sham group (sham operation group): only abdominal operation, without cecal ligation and perforation;

[0047] CLP group: establish sepsis model, without strain intervention;

[0048] CLP+Rum-307 group (treatment group): after antibiotic gavage, Rum-307 was continuously gavaged for 7 days before CLP was performed;

[0049] Sham+Rum-307 group (sham intervention group): after antibiotic gavage, only abdominal operation was performed after Rum-307 gavage.

[0050] Effect:

[0051] Intestinal barrier recovery: the intestinal permeability of the treatment group mice was significantly reduced, and the plasma lipopolysaccharide (LPS) level was significantly lower than that of the model group, indicating that the strain promoted the repair of the intestinal barrier.

[0052] Improvement of lung injury: lung tissue inflammation infiltration and hemorrhage were significantly improved compared with the model group. (see Figure 1 )

[0053] Lung wet / dry ratio: the lung wet / dry ratio of the treatment group mice was significantly reduced (7.5±0.4 for the model group and 5.8±0.3 for the treatment group, p<0.01).

[0054] Pathological score: Lung tissue inflammation infiltration and injury score was significantly improved compared with the model group. (See Figure 2 )

[0055] Inflammatory factor level:

[0056] The plasma TNF-α, IL-6 and IL-1β levels of the treatment group mice decreased significantly (about 50% respectively).

[0057] Anti-inflammatory factor IL-10 level increased, showing the enhancement of immune regulation function (see Figure 3 ).

[0058] It is worth noting that the rumenococcus Rum-307 has significant anti-inflammatory and intestinal barrier repair ability, and can play a protective role in systemic inflammation through regulation of the intestinal-lung axis. In the CLP model, the rumenococcus Rum-307 significantly improved lung tissue injury, reduced intestinal permeability in mice, and repaired the intestinal barrier. Acute respiratory distress syndrome (ARDS) as a severe lung injury triggered by systemic inflammation is closely related to intestinal barrier dysfunction and bacterial translocation. The rumenococcus Rum-307 inhibits the inflammatory response in the distal lung by enhancing the integrity of the intestinal barrier, reducing endotoxin leakage, and reducing bacterial transfer to lung tissue, thereby improving the pathological state of ARDS. Therefore, this strain has potential application value in the prevention and treatment of ARDS.

[0059] Example 2: Colonization ability of rumenococcus after antibiotic disruption of flora

[0060] Experimental subjects: C57BL / 6 mice, received antibiotic gavage (azithromycin, neomycin, ciprofloxacin, miconazole, 50 mg / kg, for 3 consecutive days).

[0061] Rumenococcus strain: No. Rum-307, bacterial solution concentration was 109CFU / mL.

[0062] Experimental grouping:

[0063] Antibiotic group (AB): only received antibiotic treatment, gavage with PBS once a day, no strain supplement.

[0064] Treatment group (Rum-307): supplemented with rumenococcus after antibiotic treatment, once a day for 7 consecutive days (see Figure 4 ).

[0065] Effect:

[0066] Intestinal flora recovery:

[0067] The proportion of lactic acid bacteria and bifidobacterium in the feces of the treatment group was significantly restored, while there was no obvious restoration in the antibiotic group.

[0068] The high-throughput sequencing analysis found that the intestinal flora diversity of the treatment group was significantly increased compared with the antibiotic group.

[0069] Ruminococcus colonization:

[0070] The CFU count of Ruminococcus strains in the feces of mice in the treatment group remained stable (about 107CFU / g), showing excellent colonization ability.

[0071] Example 3: Potential application of Ruminococcus under simulated clinical conditions

[0072] Model: After destroying the intestinal flora of mice by gavage with a large dose of antibiotics, the CLP model was used to simulate the real clinical conditions of sepsis patients.

[0073] Strain dosage form: Ruminococcus was freeze-dried into capsules, each containing 109CFU, and gavaged once a day.

[0074] Experimental grouping:

[0075] Antibiotic group (AB+CLP): After antibiotic treatment, CLP was received without Ruminococcus supplementation.

[0076] Treatment group (Rum-307): After antibiotic treatment, CLP was received with Ruminococcus supplementation.

[0077] Effect:

[0078] Systemic inflammation indicators:

[0079] The plasma CRP (C-reactive protein) level of the treatment group was significantly lower than that of the antibiotic group, indicating that the systemic inflammatory response was reduced.

[0080] Survival rate: During the 7-day observation period, the survival rate of mice in the treatment group was significantly improved (70% in the treatment group, 40% in the antibiotic group, p<0.05) (see Figure 5 ).

[0081] Lung tissue protection: The lung tissue structure of mice in the treatment group remained relatively intact (see Figure 6 ), and the pathological score was significantly lower than that of the antibiotic group (see Figure 7 ).

[0082] Example 4: Role of Ruminococcus Rum-307 in alleviating enterogenic sepsis

[0083] Experimental purpose: This experiment aims to evaluate the role of Ruminococcus Rum-307 in alleviating enterogenic infection and systemic bacteremia in sepsis mice, and to explore its mechanism of blocking the entry of intestinal-derived pathogens into the blood and controlling the progression of sepsis by repairing the intestinal barrier, reducing bacterial translocation, and reducing endotoxin levels.

[0084] Experimental animals and modeling methods:

[0085] Experimental animals: C57BL / 6 male mice, 8 weeks old, weighing 20-25 g.

[0086] Modeling method: Cecal Ligation and Puncture (CLP) method was used to construct the intestinal-derived sepsis model.

[0087] Strain intervention: Rum-307 bacterial solution (109CFU / mL) was administered intragastrically at 200 μL daily for 7 consecutive days.

[0088] Experimental grouping:

[0089] Sham group (sham operation group): only abdominal operation, without cecal ligation and perforation;

[0090] CLP group: sepsis model was established, without strain intervention;

[0091] CLP+Rum-307 group (treatment group): after intragastric administration of antibiotics, Rum-307 was administered intragastrically for 7 consecutive days before CLP was performed;

[0092] Sham+Rum-307 group (sham operation intervention group): after intragastric administration of antibiotics, Rum-307 was administered intragastrically, and only abdominal operation was performed.

[0093] Histological and functional assessment results:

[0094] 1. Intestinal barrier function assessment:

[0095] Plasma LPS level detection (ELISA): the plasma LPS concentration of the CLP group was significantly increased, and the LPS level of the CLP+Rum-307 group decreased by about 50% (p<0.01), indicating that the strain can repair the intestinal barrier and reduce endotoxin leakage.

[0096] FITC-dextran permeability test: the permeability of the CLP group was significantly increased, and after Rum-307 intervention, it approached the level of the Sham group.

[0097] 2. Bacterial translocation analysis:

[0098] Blood, liver, and spleen tissue bacterial culture: the positive rate of the CLP group was >80%, and that of the CLP+Rum-307 group decreased to <30% (p<0.01), significantly reducing the entry of intestinal-derived bacteria into the blood.

[0099] 3. Observation results of small intestinal tissue H&E staining Figure 8 ):

[0100] The intestinal villi of the CLP group were significantly atrophied and shortened, arranged in disorder, and accompanied by severe inflammation cell infiltration in the lamina propria and submucosa, and the intestinal wall structure was significantly destroyed, indicating that the intestinal barrier function was severely damaged.

[0101] The intestinal villi of the CLP+Rum-307 group were well restored, significantly lengthened, arranged in order, and accompanied by significantly reduced inflammation cells and improved epithelial integrity, indicating that the Rum-307 strain could promote intestinal epithelial repair and reduce tissue inflammatory response.

[0102] The tissue structure of the Sham group and the Sham+Rum-307 group was normal, and the strain was non-pathogenic.

[0103] 4. Observation results of abdominal incision healing and leakage performance Figure 9 ) :

[0104] The CLP group showed obvious redness, exudation, and scab around the abdominal incision after surgery, and some areas showed poor wound tension, indicating that the abdominal infection was severe, accompanied by intensified postoperative local inflammatory response, which was consistent with the early phenotype characteristics of enterogenic sepsis.

[0105] The CLP+Rum-307 group had significantly better incision healing than the CLP group, with no obvious exudation or redness, and good tension at the suture site, indicating that Rum-307 might promote tissue repair by reducing the migration of abdominal flora and inflammatory exudation.

[0106] The Sham group and the Sham+Rum-307 group had no obvious damage and changes, and the structure was normal.

[0107] 5. Survival rate analysis results Figure 10 ) :

[0108] According to the Kaplan-Meier survival curve analysis results:

[0109] The mortality rate of the CLP group rapidly increased after surgery, with a survival rate of 20% on the 3rd day, only 1 survived on the 7th day, and the final survival rate was 10%, indicating that the model successfully induced enterogenic sepsis and had high lethality.

[0110] The survival rate of the CLP+Rum-307 group was significantly improved to 80%, most of the deaths occurred within the first 3 days after surgery, and the survival rate remained stable thereafter, which was statistically different from the CLP group (Log-rank test, p<0.01), indicating that Rum-307 had a significant protective effect on improving the survival rate of enterogenic sepsis mice.

[0111] The survival rate of the Sham group and the Sham+Rum-307 group was 100% after surgery, indicating that the Rum-307 strain itself was non-toxic and had good biological safety.

[0112] Conclusion: Ruminococcus sp. Rum-307 can significantly reduce the translocation of intestinal bacteria, inhibit systemic septic reaction, and effectively block the intestinal-blood transmission chain by repairing the intestinal barrier, reducing permeability and endotoxin leakage, thereby playing a significant protective role in the prevention and treatment of intestinal sepsis and having good biological safety and clinical transformation potential.

[0113] Example 5: Role of Ruminococcus sp. Rum-307 in relieving sepsis-associated multiple organ dysfunction syndrome (MODS)

[0114] Experimental purpose: This experiment aims to verify the potential therapeutic effect of Ruminococcus sp. strain Rum-307 in relieving CLP-induced multiple organ dysfunction syndrome (MODS), and to verify its anti-inflammatory protective effect and survival benefit through histological analysis of organs such as liver, kidney, and spleen and survival rate evaluation.

[0115] Experimental animals and modeling methods:

[0116] Experimental animals: C57BL / 6 male mice, 8 weeks old, weighing 20-25g.

[0117] Modeling method: Cecal Ligation and Puncture (CLP) method is used to induce sepsis and form a typical MODS pathological state.

[0118] Strain intervention: Rum-307 bacterial solution (concentration 109CFU / mL) is administered orally 200μL daily for 7 consecutive days.

[0119] Experimental grouping:

[0120] Sham group (sham operation group): only abdominal operation, without cecal ligation and puncture;

[0121] CLP group: establish sepsis model, without strain intervention;

[0122] CLP+Rum-307 group (treatment group): after antibiotic administration, Rum-307 is administered orally for 7 consecutive days before CLP;

[0123] Sham+Rum-307 group (sham intervention group): after antibiotic administration, Rum-307 is administered orally, and only abdominal operation is performed.

[0124] Histological evaluation and results:

[0125] 1. Spleen tissue observation results Figure 11 )

[0126] The spleen tissue of the CLP group showed severe damage, the white pulp area structure was obviously destroyed, the red pulp area was obviously expanded, the lymphocytes were depleted, the tissue was loose, and a large number of neutrophil infiltrations were visible, indicating significant immune organ dysfunction and systemic hyperinflammatory state.

[0127] The spleen tissue structure of the CLP+Rum-307 group was significantly improved, the white pulp was reconstructed, the red pulp density was restored, and the number of inflammatory cells was significantly reduced, indicating that Rum-307 intervention can effectively alleviate the immune organ damage and hyperinflammatory state induced by CLP.

[0128] The spleen tissue structure of the Sham group and the Sham+Rum-307 group was complete, indicating that the strain was safe.

[0129] 2. Kidney tissue observation results Figure 12 )

[0130] The CLP group: glomerular epithelial cells were swollen, renal tubular lumen was narrowed or even blocked, accompanied by obvious interstitial edema and inflammatory cell infiltration, indicating typical sepsis-related acute kidney injury.

[0131] CLP+Rum-307 treatment group: glomerular and renal tubular structures recovered well, interstitial edema and inflammatory cell numbers decreased significantly, and kidney injury was significantly alleviated compared with the model group, indicating that Rum-307 has a protective effect on sepsis-related kidney injury.

[0132] Sham and Sham+Rum-307 groups: renal tubules were arranged in order, and glomerular structure was normal.

[0133] 3. Liver tissue observation results Figure 13 )

[0134] The CLP group: hepatocytes showed extensive vacuolar degeneration, liver cords were disordered, accompanied by obvious inflammatory cell infiltration in the portal area, and central vein dilation, indicating typical sepsis-related liver injury.

[0135] CLP+Rum-307 treatment group: hepatocytes were arranged in order, liver cord structure was reconstructed, and inflammatory cells around the central vein were significantly reduced, indicating that Rum-307 has the effect of alleviating sepsis-related liver injury.

[0136] Sham and Sham+Rum-307 groups: liver tissue was normal and no abnormalities were found.

[0137] 4. Survival rate result analysis Figure 14 )

[0138] According to the analysis results of the Kaplan-Meier survival curve:

[0139] Sham group: survival rate was 100%;

[0140] CLP group: survival rate decreased sharply, dropped to <20% on day 3, only 10% on day 7;

[0141] CLP+Rum-307 group: survival rate increased to 90%, statistically significant difference compared with CLP group (Log-rank test, p<0.01).

[0142] Sham+Rum-307 group: survival rate 100%, indicating that the strain is non-toxic and has good biological safety.

[0143] Conclusion:

[0144] In the CLP-induced MODS mouse model, Rum-307 significantly alleviated the tissue structure damage and inflammatory response of organs such as liver, kidney, and spleen, suggesting that it can play an immune protective role by repairing the intestinal barrier, inhibiting systemic inflammatory response, and regulating the gut-organ axis. The Sham+Rum-307 group did not show tissue damage, further demonstrating its good biological safety. This result provides experimental evidence and histological support for the application of Rum-307 in the treatment of multiple organ dysfunction syndrome.

[0145] Example 6: Industrial production of the Rum-307 strain

[0146] Strain culture: RCM medium was used for anaerobic culture at 37°C for 24 hours, and the bacterial solution was collected and concentrated.

[0147] Freeze-drying storage: Add protectants (skim milk and lactose) to the bacterial solution, freeze-dry to make powder.

[0148] Application form: The strain powder is prepared into capsules and oral solutions for easy storage and transportation.

[0149] Effect

[0150] Storage stability: After 6 months of storage at 4°C, the bacterial activity retention rate of the freeze-dried powder is more than 95%.

[0151] Applicability: The product is suitable for oral treatment of sepsis and related lung injury, and is easy to popularize and apply.

[0152] In addition, it should be understood that although the present specification is described in terms of embodiments, each embodiment does not necessarily contain only one independent technical solution, and the description of the specification is only for the sake of clarity. The skilled person should consider the specification as a whole, and the technical solutions in each embodiment can be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A strain of Ruminococcus, characterized in that, The cell strain is Rum-307, and the preservation number is CGMCC No. 46385.

2. A probiotic agent, characterized in that, The probiotic agent comprises the strain of the rumenococcus as claimed in claim 1.

3. The probiotic agent of claim 2, wherein the probiotic agent is a tablet. The concentration of the bacterial solution of the strain of the rumenococcus is 109 CFU / mL.

4. Use of the strain of the rumenococcus as claimed in claim 1 or the probiotic agent as claimed in claim 2 in the preparation of a drug for relieving or treating sepsis-related lung injury.

5. Use of the strain of the rumenococcus as claimed in claim 1 or the probiotic agent as claimed in claim 2 in the preparation of a drug for relieving or treating acute respiratory distress syndrome.

6. Use of the strain of the rumenococcus as claimed in claim 1 or the probiotic agent as claimed in claim 2 in the preparation of a drug for relieving or treating enterogenic sepsis.

7. Use of the strain of the rumenococcus as claimed in claim 1 or the probiotic agent as claimed in claim 2 in the preparation of a drug for relieving or treating multiple organ dysfunction syndrome.

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