Application of ackermann muciniphile or external vesicles thereof in preparation of drugs for treating schistosomiasis

Abstract

The invention belongs to the technical field of biological medicines, and relates to application of Ackermann muciniphile or its external vesicles in preparation of a drug for treating schistosomiasis. The anti-infection immunity of a host is enhanced by adjusting intestinal flora balance (recovering diversity and composition) and improving immune response (adjusting macrophage, CD8 + T cell recruitment and Th1 / Th2 balance); meanwhile, the intestinal barrier function is improved, and pathogen invasion and inflammation are reduced; hepatic granuloma and hepatic fibrosis caused by schistosome infection are obviously relieved, and the liver function is improved; the key effect of the MIF gene in immunoregulation is disclosed, and a new direction is provided for schistosomiasis immunotherapy. Besides, the probiotics are high in treatment safety and free of obvious side effects, can be combined with chemotherapy to enhance the curative effect and reduce the side effects and drug resistance of chemical drugs, provides a lasting and comprehensive adjuvant therapy scheme for the schistosomiasis, and has important clinical application potential.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to an application of Akkermansia muciniphila or its exovesicles in the preparation of a drug for treating schistosomiasis. Background Art

[0002] Schistosomiasis, a parasitic disease caused by schistosomes, is widespread in tropical and subtropical regions and poses a significant threat to global public health. According to the World Health Organization, approximately 264 million people worldwide will require preventive chemotherapy for schistosomiasis in 2022, and approximately 770 million people live in areas at potential risk of infection. Currently, the treatment of schistosomiasis relies on praziquantel, but this drug has issues such as poor solubility, the risk of drug resistance, and limited protection against reinfection. New treatment strategies are urgently needed.

[0003] Schistosoma japonicum ( Schistosoma japonicum , S. japonicum The worm, a parasite that inhabits the portal mesenteric vein, produces eggs after mating, which are excreted in feces. The eggs are the primary pathogenic stage of schistosomiasis. Soluble antigens in the eggs trigger an immune response, leading to granulomas and subsequent fibrosis, which contribute to schistosomiasis lesions.

[0004] Recent studies have shown that schistosomiasis infection is also associated with intestinal flora imbalance. Akkermansia muciniphila , A. muciniphila ) plays an important role in various disease models by maintaining intestinal barrier function, improving metabolism and regulating immunity.

[0005] Prior art CN118217265A discloses a probiotic exosome loaded with a chemotherapy drug and a PDT photosensitizer, wherein the probiotic exosome is extracted from probiotics, and the probiotics are selected from at least one of Lactobacillus rhamnosus, Escherichia coli, Lactobacillus plantarum and Akkermansia muciniphila.

[0006] Prior art CN119770525A discloses a muciniphilic Akkermansia Akkermansia muciniphila ) or its extracellular vesicles in the preparation of drugs for slowing down alcohol-induced avascular necrosis of the femoral head.

[0007] Prior art CN115671141A discloses the use of a probiotic and its outer membrane vesicles in the preparation of an anti-smoking related disease preparation. From the culture supernatant of Akkermansia muciniphila (Akk bacteria), Akkermansia muciniphila outer membrane vesicles (AkkOMV) were extracted by density gradient centrifugation, filtration, concentration and exosome extraction reagent chromatography. By constructing a smoking-induced COPD mouse model and intervening with Akk bacteria and / or AkkOMV, the relevant physiological characteristics of the mice after the intervention were detected, which confirmed that Akk bacteria and its AkkOMV can significantly reduce multiple system diseases such as respiratory, cardiovascular and cerebrovascular diseases and metabolic diseases caused by smoking, and promote the repair of multiple organ damage. The application and industrialization prospects in the field of prevention and treatment of systemic diseases caused by smoking are considerable.

[0008] Prior art CN115518079A discloses the use of a probiotic and its outer membrane vesicles in the preparation of a preparation for the prevention and treatment of bronchial asthma. Akkermansia muciniphila (Akk bacteria) culture supernatant was extracted by density gradient centrifugation, filtration, concentration, and chromatography with an exosome extraction reagent. An asthma mouse model was established and intervention was performed using Akk bacteria / Akk OMVs. Testing of the relevant physiological characteristics of the mice after intervention confirmed that Akk bacteria and its Akk OMVs inhibited airway and lung tissue inflammation, reduced airway mucus secretion, and had immunomodulatory functions. These probiotics can be used as an alternative to existing drugs or as an adjunct to therapeutic drugs for the preparation of drugs, foods, and health products for the improvement of acute and chronic asthma.

[0009] Prior art CN120078815A discloses the use of Akkermansia muciniphila in the preparation of products for treating kidney damage associated with diabetic metabolic diseases. The Akkermansia muciniphila, deposited under CGMCC No. 20955, can significantly reduce blood urea nitrogen, serum creatinine, and urine protein, improving renal function. It can also alleviate renal oxidative stress by lowering malondialdehyde levels and increasing SOD, CAT, and GSHPx activities. It can also inhibit the TLR4 / NFκB pathway, reducing TNFα and IL1β secretion and alleviating inflammatory responses. Ultimately, it exerts renal protective effects through antioxidant, anti-inflammatory, and anti-fibrotic effects.

[0010] Prior art CN116211896A discloses the use of Akkermansia muciniphila JF3 to improve tissue fibrosis and repair mucosal damage in the treatment of radiation-induced proctopathy. Studies have shown that Akkermansia muciniphila JF3 can effectively improve rectal fibrosis, rectal mucosal damage, anal damage, and colorectal inflammation caused by radiation-induced proctopathy. Therefore, the new Akkermansia muciniphila JF3 strain could be used as a potentially safe live bacterial drug for the treatment of rectal fibrosis, rectal mucosal damage, anal damage, and colorectal inflammation caused by radiation-induced proctopathy.

[0011] Prior art (Jenkins TP, et al. Schistosoma mansoni infection is associated with quantitative and qualitative modifications of the mammalian intestinal microbiota[J]. Sci Rep, 2018, 8(1):12072 and Floudas A, et al. Schistosoma mansoni Worm Infection Regulates the Intestinal Microbiota and Susceptibility to Colitis[J]. Infect Immun,2019,87(8):e00275-19.)disclosed Schistosoma mansoni( S. mansoni ) The α diversity of intestinal microorganisms in mice infected with both male and female worms was reduced, while the β diversity was significantly increased, and the abundance of Akkermansia muciniphila, Lactobacillus, Alistipes, and Bacteroides increased.

[0012] Prior art (Chen H, et al. Metagenomic analysis of the intestinal microbiome reveals the potential mechanism involved in Bacillus amyloliquefaciens in treating schistosomiasis japonica in mice. MicrobiolSpectr 12:e03735-23.) B. amyloliquefaciens Intervention for infection S. japonicum To investigate the effect of different strains on the intestinal flora of mice, a radar chart analysis was performed to show the composition of the four groups of intestinal flora. Among the top 10 species in relative abundance, Akkermansia muciniphila 、 Bacteroides caecimuris and Bacteroides sp. CBA7301 It was significantly increased in the SJ group.

[0013] based on A. muciniphila 、 A. muciniphila Extracellular vesicles (Akk-Evs) and their secretory proteins, and the development of new strategies for the treatment of schistosomiasis regulated by microbiota to address its drug resistance, reinfection and treatment issues are of great significance in promoting the progress of schistosomiasis prevention and control. Summary of the Invention

[0014] The present invention first provides an application of Akkermansia muciniphila or its exovesicles, wherein the application is as follows; a) Preparation of medicaments for treating schistosomiasis; b) Preparation of drugs for treating schistosoma japonicum infections.

[0015] In certain embodiments, the treatment is to modulate the intestinal flora after Schistosoma japonicum infection.

[0016] In certain embodiments, the treatment is to improve the immune response after Schistosoma japonicum infection.

[0017] In certain embodiments, the treatment is to reduce intestinal inflammation following Schistosoma japonicum infection.

[0018] In certain embodiments, the treatment is to alleviate liver fibrosis caused by Schistosoma japonicum infection.

[0019] In certain embodiments, the schistosome is Schistosoma japonicum S. japonicum .

[0020] In certain embodiments, A. muciniphila or Akk -EVs is administered at an appropriate dose of probiotics or exosomes, which can significantly restore the diversity and balance of intestinal flora and increase the abundance of beneficial flora.

[0021] In certain embodiments, A. muciniphila or Akk -EVs treatment can significantly regulate the host immune response and promote the proliferation of macrophages and CD8 + Recruitment of T cells and restoration of Th1 / Th2 immune balance.

[0022] In certain embodiments, A. muciniphila or Akk -EVs treatment can significantly reduce S. japonicum Infection causes accumulation of Schistosoma japonicum eggs in the small intestine and damage to intestinal villi. S. japonicum Infection causes an increase in the length of intestinal villi.

[0023] In certain embodiments, A. muciniphila or Akk -EVs treatment can alleviate liver damage, including reducing liver granuloma formation and slowing the progression of liver fibrosis.

[0024] The present invention also provides a method for evaluating the effect of MIF on the MIF deficiency mouse model. A. muciniphila or its extracellular vesicle therapy on the immune response, suggesting a key role for MIF in this treatment.

[0025] In certain embodiments, A. muciniphila orAkk The active ingredient of -EVS is provided in an oral or other form, and the dosage is suitable for treating Schistosoma japonicum infection.

[0026] The present invention also provides a method for treating S. japonicum Probiotic composition for treating infection, comprising A. muciniphila or Akk -EVs as an active ingredient is used to treat Schistosoma japonicum infection by regulating intestinal flora, improving immune response and alleviating liver fibrosis.

[0027] The present invention also provides an application of the composition, wherein the application is one of the following: a) Preparation of medicaments for treating schistosomiasis; b) preparing medicaments for treating schistosoma japonicum infection; The composition comprises Akkermansia muciniphila and its extracellular vesicles as effective ingredients.

[0028] In certain embodiments, the composition includes a probiotic composition.

[0029] The present invention also provides a method for treating schistosoma japonicum infection in vitro, comprising the step of administering Akkermansia muciniphila or Akkermansia muciniphila exovesicles or a composition comprising Akkermansia muciniphila or Akkermansia muciniphila exovesicles.

[0030] The present invention also provides a combined treatment method for improving the in vitro anti-schistosomal treatment effect, which combines Akkermansia muciniphila or Akkermansia muciniphila exovesicles or a composition containing Akkermansia muciniphila or Akkermansia muciniphila exovesicles with chemotherapy to enhance the anti-schistosomal treatment effect and prevent long-term complications by improving immune response, intestinal health and liver function.

[0031] Compared with the prior art, the present invention has at least the following beneficial effects: 1. Effectively restore the balance of intestinal flora: A. muciniphila and Akk -EVs treatment can significantly regulate the composition of intestinal flora, restore the diversity and balance of the flora, and help alleviate the dysbacteriosis caused by schistosomiasis infection.

[0032] 2. Improve immune response: by regulating immune cells (such as macrophages and CD8 + T cells) and restore the Th2 / Th1 immune balance, A. muciniphila and Akk -EVs treatment can enhance the host's immune response and improve immunity against schistosoma japonicum infection.

[0033] 3. Improve intestinal barrier function: The treatment of the present invention can effectively regulate the intestinal barrier function, reduce the invasion of harmful pathogens, and thus alleviate intestinal inflammatory response.

[0034] 4. Relieve liver fibrosis: The probiotic treatment of the present invention can significantly reduce liver damage caused by schistosoma japonicum infection, including liver granuloma formation and liver fibrosis, slow down the progression of the disease, and improve the functional status of the liver.

[0035] 5. The role of MIF in immune regulation: This paper reveals the role of MIF gene in A. muciniphila The important role of MIF in immune regulation during the treatment process provides new ideas for future research on the potential of MIF in schistosomiasis immunotherapy.

[0036] 6. No toxic side effects: As a probiotic treatment, the method of the present invention has low toxicity and side effects, is suitable for long-term use, and as an adjuvant treatment for chemotherapy, helps to reduce the side effects and drug resistance problems of chemical drugs.

[0037] 7. Potential combination therapy strategies: This treatment approach can be combined with traditional chemotherapy to improve immune response and intestinal health through probiotics, thereby enhancing the effectiveness of anti-schistosomiasis treatment and helping to prevent long-term complications of schistosomiasis, providing a more comprehensive treatment option.

[0038] In summary, the present invention provides a novel and effective adjuvant treatment method for schistosomiasis, which can provide a more lasting and comprehensive therapeutic effect by regulating intestinal flora, enhancing immune response and alleviating liver fibrosis, and has important clinical application potential. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 ,yes [[ID=4 3]]Akk -Evs identification results; Figure A is a representative transmission electron microscope image, the scale bar is 200 nm; Figure B is the particle size analysis result; Figure C is Akk -Main protein distribution diagram of Evs protein after SDS-PAGE silver staining.

[0040] Figure 2 , are the weight data records of WT mice and MIF-deficient mice; Figure A is the weekly weight change chart of wild-type mice; Figure B is the weekly weight change chart of MIF gene-deficient mice.

[0041] Figure 3 , are α-diversity analysis diagrams of mouse intestinal flora; Figures AD are Sobs, Chao1, Shannon and Simpson index diagrams of mouse intestinal flora α-diversity, respectively.

[0042] Figure 4 , is the PCoA analysis diagram of β diversity of mouse intestinal flora.

[0043] Figure 5 , are the results of flow cytometric analysis of mouse spleen lymphocytes; Figure A is the strategy diagram for sorting cell subsets using flow cytometry; Figures B and D are F4 / 80 + 、CD8a + and CD4 + Figures E and F are the percentage of CD4 + CD4 + IL4 + and CD4 + IFN-γ + Figure G shows the percentage of T cells; Figure G shows the ratio of Th2 / Th1.

[0044] Figure 6 , pathological analysis of H&E-stained sections of the small intestine; A is a representative section of the small intestine tissue after H&E staining, 200×, scale bar 20μm; Figures B and C are intestinal tissue pathology scoring; Figure D is the number of worm eggs per gram of intestinal tissue; Figure E is the intestinal villus length.

[0045] Figure 7 Figures 2 and 3 are pathological analyses of PAS-stained sections of the small intestine. Figure A is a characteristic image of a PAS-stained section of the intestine, 100×, scale bar 50 μm. Figure B is a quantitative analysis of goblet cells.

[0046] Figure 8 Figures 2 and 3 are H&E staining analysis results of liver pathological sections. Panel A shows the characteristic results of liver H&E staining (200×), scale bar 20 μm; Panel B shows the quantification of the area of ​​a single egg granuloma. Panel C shows the characteristic results of liver Masson staining (40×), scale bar 200 μm; Panel D shows the quantification of collagen area. DETAILED DESCRIPTION

[0047] In order to make the technical problems, technical solutions and advantages to be solved by the present invention clearer, a detailed description will be given below with reference to the accompanying drawings and specific embodiments.

[0048] Example 1, materials and grouping (1) Experimental animals, strains, and positive snails In the experiment, the number of male and female mice was equal (8-10 per group), aged 6 to 8 weeks, and they were all housed in a specific pathogen-free facility with free access to food and water, a 12-h day and night cycle, and an ambient temperature of 21 to 25°C. A. muciniphila The strain 33894T (ATCC BAA-835) was purchased from the Japan Collection of Microorganisms. The cercariae of Schistosoma japonicum were obtained from positive Hubei snails purchased from the Jiangsu Institute of Parasitic Diseases.

[0049] (2) Preparation of preparations A. muciniphila Suspension preparation: Culture under anaerobic conditions A. muciniphila When the cells reached the logarithmic growth phase, they were collected by centrifugation and resuspended in PBS containing 25% glycerol to adjust the concentration to 1×10 9 CFU / mL.

[0050] Akk - EVs extraction and identification: anaerobic culture A. muciniphila , when OD 600 When the nm value was 1.0, centrifuge at 11,000 × g at 4°C for 30 min, discard the pellet, and collect the supernatant. Repeat twice. The supernatant was filtered through 0.45 μm and 0.22 μm filters, and the filtrate was collected into a sealed tube. Ultracentrifuge at 200,000 × g at 4°C for 2.5 h, discard the supernatant, and resuspend the bacterial extracellular vesicle pellet in PBS and store at -80°C. Transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), SDS-PAGE protein silver staining, and BCA protein quantification were performed. Akk -Evs morphology, size and concentration, and finally prepared into Akk -Evs 50 μg / mL PBS suspension.

[0051] Results: See Figure 1 , observed by transmission electron microscopy and nanoparticle tracking analysis, Akk -Evs showed a typical spherical structure with an average diameter of 84.14±25.62 nm. Further silver staining SDS-PAGE analysis showed that Akk -Evs protein molecules are mainly concentrated in the range of 55-70 kDa, and low molecular weight proteins are more abundant.

[0052] (3) Experimental groups and intervention plan After acclimating to the environment for 7 days, WT mice and MIF KO mice were randomly divided into 4 groups, with 8-10 mice in each group, including uninfected control group + PBS gavage group (CP), S. japonicum Infected mice + PBS gavage group (SP), S. japonicum Infected mice+ A. muciniphila Oral gavage group (SA), S. japonicum Infected mice+ Akk -Evs gavage group (SE). Before infection, mice in the SA group were gavaged for 7 consecutive days. A. muciniphila Bacteria solution; mice in SE group were gavaged Akk -Evs; while the mice in the CP and SP groups were gavaged with an equal volume of PBS.

[0053] Results: See Figure 2, mice in S. japonicum The weight began to decrease in the fifth week of infection, and the A. muciniphils or Akk -Evs did not significantly improve the body weight of mice, and the same trend of body weight changes was observed in WT mice and MIF KO mice.

[0054] Example 2: Determination of 16S intestinal flora After extracting and quantifying bacterial DNA from fecal samples of the mice in the aforementioned groups, the V3-V4 hypervariable region of the 16S rRNA gene was amplified, library constructed, and sequenced to compare and analyze changes in the mouse intestinal microbiota. Alpha diversity indices, including Chao1 and Shannon indices, were calculated using mothur software, and differences in alpha diversity between groups were analyzed using the Wilcoxon rank sum test. Beta diversity of the microbial community structure was analyzed using principal component analysis (PCoA) based on the Bray-Curtis distance algorithm.

[0055] Results: See Figure 3 , A. muciniphila and Akk -Evs' intervention changed the S. japonicum Infected mice reshaped the gut microbiota, reshaping alpha and beta diversity, with differential effects between WT and MIF KO mice.

[0056] The observed species (Sobs), Chao1, and Shannon index in the SP group were significantly lower than those in the CP group (all p < 0.001), while the Simpson index showed an upward trend in the SP group (p < 0.010). A. muciniphila or Akk -Evs intervention can offset these changes, indicating that A. muciniphila and Akk -Evs intervention reshaped the alpha diversity of the mouse intestinal flora (SA p<0.050, p<0.050, p<0.001; SE p<0.050, p<0.050, p<0.010), while this intervention effect was not obvious in MIF KO mice.

[0057] See Figure 4 , PCoA analysis results based on Bray-Curtis distance showed that, S. japonicum There were significant differences in the microbial community composition between the infection group and the control group. [[ID= 83]]S. japonicum Compared with the infection group, except for the MIF KO SA group, A. muciniphila or Akk-EVs intervention also caused significant differences in microbial composition, whereas Akk The differences were most pronounced in MIF KO mice treated with -Evs.

[0058] Example 3, flow cytometry The spleens of the mice in the above groups were removed under sterile conditions, and after mechanical grinding, the spleen lymphocyte suspension was obtained using lymphocyte separation medium (density gradient centrifugation). The cell concentration was adjusted to 3×10 6 PE-labeled anti-mouse CD8a antibody and APC-labeled anti-mouse F4 / 80 antibody were added to the cells and incubated at 4°C in the dark for 20 minutes. After completion, the cells were washed twice with cell staining buffer to remove unbound antibodies. The remaining lymphocytes were resuspended in RPMI 1640 medium containing 10% fetal bovine serum, 1% penicillin / streptomycin, and 50 μmol / L β-mercaptoethanol and the cell density was adjusted to 5×10 6 Cells were stained with FITC-labeled anti-mouse CD4 antibody and incubated at 4°C for 20 minutes. TM The membrane was fixed and permeabilized using the transcription factor buffer system. PE-labeled anti-mouse IL-4 antibody and APC-labeled anti-mouse IFN-γ antibody were added and incubated in the dark at room temperature for 20 minutes. Finally, True-Nuclear TM Cells were washed with permeabilization buffer and resuspended in cell staining buffer. Cell samples were analyzed on a Cytoflex flow cytometer, and data were processed and analyzed using FlowJo 10.4 software.

[0059] Results: See Figure 5 , gavage A. muciniphila or Akk -EVs can promote the proliferation of macrophages and CD8 + T cell recruitment and regulation of Th2 / Th1 immune balance.

[0060] In MIF KO mice, S. japonicum Compared with the infected group, A. muciniphila or Akk - Evs intervention significantly increased F4 / 80 + cells (all p < 0.001) and CD8a + Cell number ( A. muciniphila The same trend was observed in WT mice, but the difference was not statistically significant.

[0061] In WT mice or MIF KO mice, infection S. japonicum Post-CD4 + The number of cells was significantly decreased (p<0.001, p<0.001); + In cells, CD4 + IL-4 + The percentage of cells (Th2 cells) increased significantly (all p < 0.001), and CD4 + IFN-γ + The proportion of cells (Th1 cells) was decreased (all p < 0.001). A.muciniphila or Akk - EVs intervention can strongly reverse these changes and increase CD4 + cells, especially Th1 cells ( Akk -Evs treatment WT p < 0.001, MIFKO p = 0.002), reduced Th2 cells ( A.muciniphila treatment WT p = 0.009, MIF KO p = 0.049; Akk Treatment with -EVs (WT p<0.001, MIF KO p=0.027) favored restoring the Th1 / Th2 balance. Although the numbers of these immune cells were lower in MIF KO mice compared with WT mice, these changes were more pronounced when MIF was deficient.

[0062] Example 4, histopathological section analysis Tissue specimens were fixed in 4% paraformaldehyde, dehydrated with graded ethanol (70% to 100%), cleared with xylene, and then immersed in paraffin (58-60°C). 5-μm serial sections were prepared using a microtome. Small intestinal tissues were stained with H&E to assess tissue damage and analyzed blindly under a microscope based on the degree of epithelial damage and inflammatory infiltration. Goblet cells were counted after PAS staining, and villus length was measured. Sections were observed under a light microscope (Olympus BX53F), and images were acquired using Olympus cellSens Standard 1.13 software. Liver tissues were stained with H&E and Masson's method, respectively. At least 20 well-defined, single egg granulomas were randomly selected from each group. The area of ​​individual granulomas and fibrosis was calculated using FijiImageJ software.

[0063] Results: See [[ID=1 00]]Figure 6 , the degree of small intestinal tissue damage in the SP group was higher than that in the SA and SE groups. A. muciniphilaThe treated mice showed lower histological scores compared with the infected group (WT p < 0.001, MIF KO p = 0.020), and the histological scores of WT mice were lower than those of MIF KO mice (p < 0.001). Akk -The histological score of SE group treated with Evs was significantly lower than that of SP group (WT p = 0.012, MIF KO p < 0.001). S. japonicum Infection significantly increased the number of worm eggs in the intestinal tissue of mice (p<0.001) and the length of intestinal villi (p<0.001), while oral administration A. muciniphila and Akk -Evs significantly reduced the number of worm eggs per gram of intestinal tissue and also reduced the length of intestinal villi. A. muciniphila The length of intestinal villi increased in the treated MIF KO mice, but there were no significant differences in other test results between WT and MIF KO mice.

[0064] See Figure 7 , S. japonicum Infection significantly reduced the number of goblet cells in the intestine (WT p<0.001; MIFKO p<0.001). A. muciniphila or Akk Treatment with -Evs significantly increased the number of goblet cells (both p < 0.001). Similar trends were observed in both WT and MIF KO mouse models. Notably, in the SA group, the number of goblet cells in MIF KO mice was higher than that in WT mice (p = 0.044), while in the SE group, the opposite trend was observed, with the number of goblet cells in MIF KO mice lower than that in WT mice (p < 0.001).

[0065] See Figure 8 , infection in WT mice and MIF KO mice S. japonicum The area of ​​single egg granuloma increased dramatically after supplementation (p < 0.001). A. muciniphila or Akk The number of single egg granulomas in mice with -Evs was significantly reduced (p < 0.001). The changes in fibrosis area determined by Masson staining were consistent with this result. S. japonicum Compared with the infected group, A. muciniphila or Akk -Evs treatment reduced collagen deposition (all p < 0.001). A. muciniphila and Akk -Evs reduced due to infection S. japonicum Resulting in egg granulomas and liver fibrosis.

[0066] The above is a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A use of Akkermansia muciniphila or its exovesicles, characterized in that: The application is one of the following; a) Preparation of medicaments for treating schistosomiasis; b) Preparation of drugs for treating schistosoma japonicum infections.

2. The use according to claim 1, characterized in that The treatment is to regulate the intestinal flora after schistosoma infection.

3. The use according to claim 1, characterized in that The treatment is to improve the immune response after schistosoma japonicum infection.

4. The use according to claim 1, characterized in that The treatment is to alleviate intestinal inflammation after schistosoma infection.

5. The use according to claim 1, characterized in that The treatment is to alleviate liver fibrosis caused by schistosoma japonicum infection.

6. The use according to any one of claims 1 to 5, characterized in that: Schistosoma japonicum ( Schistosome japonicum, S. japonicum ).

7. An application of a composition, characterized in that: The application is one of the following; a) Preparation of medicaments for treating schistosomiasis; b) preparing medicaments for treating schistosoma japonicum infection; The composition comprises Akkermansia muciniphila and its extracellular vesicles as effective ingredients.

8. The use according to claim 7, characterized in that The composition includes a probiotic composition.

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