Use of a valens enterobacter in improving reduced sperm quality

Abstract

The application belongs to the field of male infertility disease treatment, and discloses application of a valens enterobacter in improving sperm quality decline. Ileibacterium valens Liu-M1, which is preserved in China Center for Type Culture Collection (CCTCC) and has a preservation number of CCTCC M 20252545. The strain of the application is obtained by using a bacterial separation and identification method to separate and identify a fresh fecal sample of a high-fat diet mouse intervened by inulin. In vivo research finds that the live valens enterobacter can improve the reproductive function of obese male mice, has the effects of improving testosterone secretion, repairing spermatogenesis function, improving sperm quality and embryo development capacity and the like. Experimental results of the application show that the valens enterobacter can significantly improve obesity-related sperm quality decline, which indicates that the valens enterobacter has the potential to become a microbial candidate drug for treating obesity male reproductive function.

Description

Technical Field

[0001] This invention belongs to the field of treatment of male infertility, and more specifically, relates to the application of *Enterobacter valerianum* in improving declining sperm quality. Background Technology

[0002] According to a World Health Organization report, approximately 17.5% of adults worldwide are affected by infertility, and about half of these cases can be attributed to male factors. Decreased sperm quality, including reduced sperm count, decreased motility, and increased abnormal sperm morphology, is one of the leading causes of male infertility. With the increasing global obesity rate, obesity has become a significant risk factor for declining sperm quality in men. Currently, clinical treatments for decreased sperm quality (especially obesity-related sperm quality decline) are limited, and the efficacy is often unsatisfactory.

[0003] In recent years, the concept of the "gut-testis axis" has provided a novel perspective for understanding this issue, revealing that the gut microbiota, as a core bridge, can remotely regulate testicular function through itself and its metabolically active substances. Current research has found that gut microbial dysbiosis induced by a high-fat diet can impair spermatogenesis and sperm motility, but the core strains responsible for this effect have not yet been clearly identified and isolated. Summary of the Invention

[0004] To address the aforementioned deficiencies or improvement needs of existing technologies, the present invention aims to provide an application of *Enterobacter valens* in improving declining sperm quality. A strain of *Enterobacter valens* was isolated and identified from fresh feces of mice on a high-fat diet treated with inulin using bacterial isolation and identification methods. Ileibacterium valens Liu-M1, utilizing *Enterobacter valerianis* Ileibacterium valens The new strain Liu-M1 can be used to improve declining sperm quality.

[0005] To achieve the above objectives, according to a first aspect of the present invention, a *Enterobacter valens* strain is provided. Ileibacterium valens Liu-M1, characterized by its classification as *Enterobacter valens* (… Ileibacterium valens (), deposited at the China Center for Type Culture Collection (CCTCC), accession number CCTCC M20252545.

[0006] According to a second aspect of the present invention, the present invention provides the above-mentioned *Enterobacter valens*. Ileibacterium valens The method for isolating and culturing Liu-M1 is characterized by,

[0007] The isolation step involved using bacterial isolation and identification methods to isolate the bacteria from the fresh feces of mice on a high-fat diet treated with inulin; wherein the feed administered to the high-fat diet mice contained 45% fat and was also supplemented with inulin.

[0008] The cultivation process was carried out in an anaerobic environment at 37°C. The anaerobic environment consisted of 85 vol% N2, 10 vol% CO2, and 5 vol% H2. The culture medium used was a modified Brucella agar medium with the following components: 10.0 g / L peptone, 2.0 g / L yeast extract, 10.0 g / L tryptone, 5.0 g / L sodium chloride, 1.0 g / L glucose, 0.1 g / L sodium bisulfite, 50 mL / L defibrinated sheep blood, 5 mg / L heme chloride, and 1 mg / L vitamin K1.

[0009] According to a third aspect of the present invention, a microbial preparation is provided, characterized in that it comprises:

[0010] a) The aforementioned *Enterobacter valerian* Ileibacterium valens Liu-M1, or its bacterial culture, or its metabolites;

[0011] and b) pharmaceutically or food-grade acceptable carriers.

[0012] As a further preferred embodiment of the present invention, the microbial preparation is a preparation of live bacteria, including the aforementioned *Enterobacter valens*. Ileibacterium valens Liu-M1.

[0013] As a further preferred embodiment of the present invention, the formulation is in the form of capsules, tablets, powders or liquids.

[0014] According to a fourth aspect of the present invention, the present invention provides the above-mentioned *Enterobacter valens*. Ileibacterium valens Application of Liu-M1 or the above-mentioned microbial preparations in the preparation of drugs to improve decreased sperm quality.

[0015] As a further preferred embodiment of the present invention, the decline in sperm quality specifically refers to obesity-related decline in sperm quality.

[0016] As a further preferred embodiment of the present invention, the *Enterobacter valens* Ileibacterium valens Liu-M1, or its bacterial culture, or its metabolites have at least one of the following effects:

[0017] a) Increase sperm concentration;

[0018] b) Improve sperm motility, wherein improving sperm motility includes at least one of increasing the percentage of progressively motile sperm or increasing the percentage of total motile sperm;

[0019] c) Reduce sperm abnormality rate;

[0020] d) Improve embryonic developmental potential;

[0021] e) Improve the structure of the seminiferous tubules in the testes;

[0022] f) Increase the number of spermatogenic cells;

[0023] g) Increase serum testosterone levels.

[0024] As a further preferred embodiment of the present invention, the spermatogenic cells include DAZL. + Cells, SYCP3 + Cells, TNP1 + Cells, WT1 + Cells and PGK2 + One or more of them in the cell.

[0025] Through the above-described technical solutions conceived in this invention, compared with the prior art, this invention, through rigorous animal experiments, has pioneered the discovery of a new *Enterobacter valens* species [the "Enterobacter valens" mentioned in this invention refers to the species with the Latin name...] Ileibacterium valens ( I. valens (bacteria). In this invention, unless otherwise specified, this term is synonymous with (bacteria). Ileibacterium valens ( I. valens () has the same meaning, but specifically refers to the strain with accession number CCTCC M20252545. Ileibacterium valens [Liu-M1] can directly act on the spermatogenesis process, significantly improving sperm quality and opening up a new application direction for using this strain to improve male sperm quality (especially in obese men) and alleviate spermatogenesis disorders. Taking Example 2 below as an example, in vivo studies have found that live [sperm]... I. valens The bacteria can improve the reproductive function of obese male mice, and have the effects of increasing testosterone secretion, repairing spermatogenesis, and improving sperm quality and embryonic development. The above experimental results indicate... I. valens The bacteria can significantly improve obesity-related sperm quality decline, suggesting... I. valens Bacteria have the potential to become microbial drug candidates for treating male reproductive dysfunction, especially in obese men.

[0026] The present invention uses I. valensThe bacteria were isolated from the fresh feces of inulin-treated high-fat diet mice using bacterial isolation and identification methods (the diet of the high-fat diet mice contained 45% fat and was supplemented with 10 wt% inulin to achieve inulin intervention), and cultured under anaerobic conditions; I. valens The bacteria are Gram-positive bacteria belonging to the phylum Firmicutes, family Trichophyceae, and genus Enterobacter (as described below). Figure 2 (As shown).

[0027] The present invention uses I. valens The bacteria can fundamentally improve sperm count, motility, and the rate of normal morphology. Taking Example 2 below as an example, this invention was verified through in vivo experiments: [The following text appears to be a separate, unrelated sentence fragment:] Daily [treatment / treatment] of mice with impaired reproductive function due to obesity... I. valens After continuous intervention for a certain period, this invention can significantly improve sperm count, motility, and normal morphology rate in male animals. Furthermore, this invention can particularly enhance offspring development potential by increasing the blastocyst rate, and also has a direct effect on improving testosterone levels and the structural repair of seminiferous tubules.

[0028] In summary, this invention, based on the innovative concept of the "gut-testis axis," systematically studies... I. valens The direct effects of bacteria on the reproductive system in an obesity model were first revealed. I. valens The novel use of bacteria in improving declining sperm quality (especially obesity-related decline) provides a new direction for the development of drugs related to the reproductive health of obese men. Attached Figure Description

[0029] Figure 1 For Valens ileum [ Ileibacterium valens [Liu-M1] Colony morphology on solid culture medium.

[0030] Figure 2 For Valens ileum [ Ileibacterium valens Image of Gram staining results for Liu-M1].

[0031] Figure 3 A comparison chart of testicular and epididymal organ coefficients for each group of mice; among them, Figure 3 From left to right, the charts show the comparison of testicular organ coefficients and epididymal organ coefficients in each group of mice.

[0032] Figure 4 A comparison chart of serum testosterone levels in mice from different groups.

[0033] Figure 5 H&E staining images of seminiferous tubules in testicular tissue of mice in each group; among them, Figure 5From left to right: H&E staining of seminiferous tubules in testicular tissue of control group mice, H&E staining of seminiferous tubules in testicular tissue of high-fat group mice, and high-fat + I. valens H&E staining of seminiferous tubules in testicular tissue of mice; the scale bar in the figure corresponds to an actual size of 50 μm.

[0034] Figure 6 A comparison chart showing the proportion of seminiferous tubules containing mature sperm in each group of mice.

[0035] Figure 7 DAZL was injected into the seminiferous tubules of mice in each group. + (Spermatogonia markers), SYCP3 + (Spermatocyte markers), TNP1 + (Sperm cell markers), WT1 + (Supporting cell markers) and PGK2 + Comparison of immunofluorescence staining for (mature sperm markers); among which, Figure 7 Divided into 5 rows from top to bottom, each row shows the SYCP3 levels in the seminiferous tubules of mice in each group. + Immunofluorescence staining comparison of spermatocyte markers, and PGK2 in the seminiferous tubules of mice in each group. + Immunofluorescence staining comparison of (mature sperm markers), and WT1 in the seminiferous tubules of mice in each group. + Immunofluorescence staining comparison of (supporting cell markers), and TNP1 in the seminiferous tubules of mice in each group. + Immunofluorescence staining comparison of sperm cell markers, and DAZL in the seminiferous tubules of mice in each group. + Immunofluorescence staining comparison images of (spermatogonia markers); each row of immunofluorescence staining comparison images corresponds from left to right to the control group, high-fat group, and high-fat+ group. I. valens Group; the scale length in the figure corresponds to the actual size of 20μm.

[0036] Figure 8 DAZL was injected into the seminiferous tubules of mice in each group. + (Spermatogonia markers), SYCP3 + (Spermatocyte markers), TNP1 + (Sperm cell markers), WT1 + (Supporting cell markers) and PGK2 + A comparison chart of average fluorescence density values ​​of (mature sperm markers); among which, Figure 8 From left to right, these correspond to SYCP3 in the seminiferous tubules of mice in each group. + Comparison of average fluorescence density values ​​of (spermatocyte markers) and PGK2 in seminiferous tubules of mice in each group. +Comparison of average fluorescence density values ​​of (mature sperm markers) and WT1 in seminiferous tubules of mice in each group. + Comparison of average fluorescence density values ​​of (supporting cell markers) and TNP1 in seminiferous tubules of mice in each group. + Comparison of average fluorescence density values ​​of sperm cell markers; DAZL in seminiferous tubules of mice in each group. + Comparison of average fluorescence density values ​​of (spermatogonia markers)

[0037] Figure 9 This is a comparison chart of sperm motility in different groups of mice; among them, Figure 9 From left to right: Comparison of sperm motility in the control group mice, comparison of sperm motility in the high-fat group mice, and high-fat + I. valens Comparison of sperm motility in mice from different groups.

[0038] Figure 10 These are comparative images of sperm morphology in different groups of mice; among them, Figure 10 From left to right: Comparison of sperm morphology in the control group, comparison of sperm morphology in the high-fat group, and high-fat + I. valens Comparison of sperm morphology in mice from different groups; the scale bar in the figure corresponds to the actual size of 25μm.

[0039] Figure 11 Comparative images of mouse embryos developing into two-cell stage and blastocyst stages in each group; among them, Figure 11 The images are divided into two rows from top to bottom. Each row shows a comparison of mouse embryos developing into two-cell stage and then a comparison of mouse embryos developing into blastocysts. From left to right, each row of comparison images corresponds to the control group, the high-fat group, and the high-fat+ group. I. valens Group; the scale length in the figure corresponds to the actual size of 50μm.

[0040] Figure 12 This is a comparative graph showing the quantitative analysis of forward motility, sperm abnormality rate, two-cell stage rate, and blastocyst rate in mice of different groups; among them, Figure 12 The data is divided into two rows from top to bottom. The first row, from left to right, shows the comparison of the forward motility sperm rate and the abnormal sperm rate of each group of mice. The second row, from left to right, shows the comparison of the 2-cell development rate and the blastocyst development rate of each group of mice. Detailed Implementation

[0041] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0042] Example 1: Isolation and identification of Enterobacter valerianis:

[0043] (1) Isolation and culture of bacteria

[0044] Eight 40-week-old male specific pathogen-free (SPF) C57BL / 6J mice were acclimatized to a standard diet (AIN-93M; ResearchDiets) for one week, and then fed a high-fat diet supplemented with 10% (w / w) inulin (45% fat, D12451 + 10% inulin; ResearchDiets) for 16 weeks to obtain inulin-treated high-fat diet mice. Fresh fecal samples were collected from the inulin-treated mice and homogenized in sterile PBS containing anaerobic agents (L-cysteine ​​and sodium sulfide). After vortexing and low-speed centrifugation, the supernatant was collected and serially diluted 10-fold with sterile PBS under sterile anaerobic conditions (10... - ¹ to 10 -7 100 μL of each dilution was spread onto modified Brucella agar plates (components: peptone 10.0 g / L, yeast extract 2.0 g / L, tryptone 10.0 g / L, sodium chloride 5.0 g / L, glucose 1.0 g / L, sodium bisulfite 0.1 g / L, defibrinated sheep blood 50 mL / L, heme chloride 5 mg / L, vitamin K1 1 mg / L), and incubated at 37°C in an anaerobic environment (85 vol% N2, 10 vol% CO2, 5 vol% H2) for 96 hours and photographed. The culture was then subjected to 10 [units of measurement - missing from original text] with sterile PBS under anaerobic conditions. -4 The results of the diluted culture are as follows Figure 1 As shown. Its Gram staining positive result is as follows. Figure 2 As shown.

[0045] (2) Bacterial DNA extraction and identification

[0046] Isolated colonies with a diameter of 1-2 mm were selected, washed with sterile PBS, and bacterial genomic DNA was obtained using a commercial microbial DNA extraction kit. PCR amplification was performed using universal primers 357F and 806R. The amplified products were sequenced by Shanghai Maichuan Biotechnology Co., Ltd. Sequencing analysis using reference sequences in the NCBI database identified the isolated strain as a novel *Enterobacter valens*, and it was named... Ileibacterium valens Liu-M1 is deposited at the China Center for Type Culture Collection (CCTCC), Wuhan University, Wuhan, China, with accession number CCTCC M 20252545 and deposit date of November 13, 2025.

[0047] Example 2: *Enterobacter valerate* improves decreased sperm quality:

[0048] After acclimatizing for one week, 24 40-week-old SPF-grade male C57BL / 6J mice were randomly assigned to three groups (n=8 per group):

[0049] a) Control group, namely, the "Control diet" (CD) group;

[0050] b) High-fat group, i.e., the "High-fat diet" (HFD) group;

[0051] c) High-fat + I. valens Bacterial community, namely, high-fat + I. valens Group;

[0052] The control group mice were fed a standard diet (product number: AIN-93M; purchased from: ResearchDiets), while the other two groups were fed a high-fat diet (45% fat energy ratio, product number: D12451; purchased from: ResearchDiets).

[0053] During the 12-week gavage intervention (every two days), both the CD and HFD groups received 100 μL of sterile phosphate-buffered saline, high-fat + I. valens The group was given 10 9 100 μL of sterile PBS containing live CFU. To prevent cross-contamination, each group used a sterile gavage syringe independently.

[0054] Twelve weeks later, mice were anesthetized by intraperitoneal injection of 50 mg / kg sodium pentobarbital, followed by blood collection via the abdominal aorta and sacrifice. The testes and bilateral epididymis were rapidly separated. Testicular tissue was preserved in testicular fixation solution for subsequent pathological analysis; whole blood samples were centrifuged (12,000 rpm, 15 min), and the supernatant was collected for testing testosterone levels.

[0055] Bilateral epididymal tails of mice were harvested and placed in 12-well plates, then cut into small pieces using sterile scissors. 1 mL of preheated HTF capacitation medium was added, and the plates were incubated at 37°C with 5% CO2 for 5 min to allow for complete sperm release. Finally, the proportion of forward-moving sperm was recorded using a computer-aided sperm analysis system (CASA; SAS, China).

[0056] Bilateral epididymal tails of mice were collected and placed in 12-well plates, then cut into small pieces using sterile scissors. 1 mL of preheated HTF capacitation medium was added, and the plates were incubated at 37°C with 5% CO2 for 5 min. A suitable amount of sperm suspension was collected and smeared. After air-drying, the smears were fixed with methanol and stained with 1% eosin solution for 1 h. Finally, sperm morphology was assessed: at least 500 sperm were observed from each mouse, excluding sperm with head / tail defects, blurred features, or damage, and the morphological abnormality rate was calculated.

[0057] Bilateral epididymal tails of mice were harvested and placed in 12-well plates, then cut into small pieces using sterile scissors. 1 mL of preheated HTF capacitation medium was added, and the plates were incubated at 37°C with 5% CO2 for 1 h. Ampoules of oviducts from superovulated female mice at 5 weeks gestation were placed in pre-equilibrated M2 medium, and the oocyte complex was mechanically dissected to release it. The ampoules were then cultured at 37°C with 5% CO2 for 15 min. Capacitated sperm were then added to the oocyte-containing medium and co-cultured at 37°C with 5% CO2 for 3–4 h. Fertilized zygotes were transferred to HTF medium, residual granulosa cells were mechanically removed, and the embryos were cultured stably for 30 min. Finally, the obtained single-cell embryos were cultured in vitro, and the rates of development to the 2-cell stage and blastocyst stage were recorded at 24 h and 84 h post-culture.

[0058] Experimental results showed that, compared with the HFD group mice, high-fat + I. valens The testicular organ coefficient of the group of mice was 0.3998±0.0534. vs. 0.5004±0.0794, P <0.05), epididymal organ coefficient (0.2331±0.0460) vs. 0.3139±0.0495, P <0.05) and serum testosterone levels (2.1386±0.4494). vs. 4.3293±0.5346, P <0.001) significantly increased ( Figure 3 , Figure 4 H&E staining results showed that, compared with the HFD group mice, high-fat + I. valens The number of spermatogenic cells in the seminiferous tubules of the mice in this group was significantly increased, and the cells were arranged more tightly and neatly. The number of mature sperm in the tubules was also significantly increased (24.8800±5.7840). vs. 38.0880.6880±4.2661, P <0.05, Figure 5 , Figure 6In the HFD group mice, detached and disordered spermatogenic cells were present in the seminiferous tubules, while in the high-fat group... I. valens The mice in the high-fat group showed significant improvement; from the basement membrane to the lumen, high-fat + I. valens The group shows a more complete and orderly hierarchy of spermatogenic cells (spermatogonia-spermatocytes-spermatids-spermocytes), and the seminiferous tubule structure is visible through... I. valens The bacterial intervention significantly improved the condition. Immunofluorescence staining results showed that, compared with HFD mice, high-fat + I. valens DAZL in the seminiferous tubules of mice + (Spermatogonia marker, 0.6441±0.0589) vs. 0.7848±0.0255, P <0.05), SYCP3 + (Spermatocyte marker, 0.6366±0.0486) vs. 0.8174±0.07576, P <0.05), TNP1 + (Sperm cell markers, 0.6792±0.0876) vs. 0.8213±0.0582, P <0.05), WT1 + (Supporting cell markers, 0.5944±0.0411) vs. 0.7455±0.0851, P <0.05) and PGK2 + (Mature sperm marker, 0.6094±0.0533) vs. 0.7437±0.0677, P The expression level of <0.05 was significantly increased ( Figure 7 , Figure 8 ).

[0059] In addition, compared with the HFD group, high-fat + I. valens The sperm forward motility of the mice in the group was increased (19.5960±2.1952). vs. 24.0380±1.8820, P <0.05) and a decrease in sperm abnormality rate (43.1160±2.9066). vs. 33.0460±3.4887, P <0.001)( Figure 9 , Figure 10 , Figure 12 In in vitro fertilization experiments, compared with the HFD group, high-fat + I. valens The rate of single-cell embryos developing into blastocysts in the mouse group was significantly increased (30.0726±10.1045). vs.45.6906 ± 6.6856, P <0.05, Figure 11 , Figure 12 Key indicators such as sperm count, abnormality rate, and sperm motility all indicate... I. valens Bacterial intervention can effectively improve sperm quality.

[0060] The above embodiments of the present invention construct a multi-level, multi-omics systematic evaluation system, wherein:

[0061] Histopathological level: H&E staining analysis provides direct confirmation. I. valens Bacteria have a repairing effect on the structure of seminiferous tubules, providing a morphological basis for functional improvement.

[0062] At the cell biology level: Immunofluorescence staining analysis was performed using a set of specific molecular markers (including DAZL, SYCP3, TNP1, WT1, PGK2, etc.) to systematically evaluate... I. valens The effect of bacteria on spermatogenic cell lineages. Experimental results showed that... I. valens The bacteria can effectively promote the proliferation and differentiation of cells at all stages from spermatogonia to mature sperm, demonstrating their comprehensive regulatory capabilities at the cellular level.

[0063] Functional validation level: Further evaluation is conducted by detecting sperm motility and morphological parameters, combined with in vitro fertilization experiments. I. valens The influence of bacteria on embryonic developmental potential. This series of experiments constructed a complete chain of evidence from tissue structure to cell function and then to embryonic developmental potential, systematically elucidating the influence of bacteria on embryonic developmental potential. I. valens The remarkable effect of bacteria in improving spermatogenesis demonstrates the technical advantages of this invention.

[0064] In this embodiment of the invention, a 12-week intervention period was chosen for the animal model. This duration was determined based on the physiological characteristic that the complete spermatogenesis cycle in mice is approximately 35 days. The 12-week intervention period covers at least three complete spermatogenic epithelial cycles, thereby ensuring a systematic assessment of the complete biological process from spermatogonial stem cell proliferation and differentiation to mature spermatogenesis and embryonic developmental potential. This design allows for sufficient validation of… I. valens The long-term and stable improvement of sperm quality by bacteria also conforms to the ethical and economic principles of animal experiments.

[0065] The above experiment shows that after 12 weeks of intervention, I. valensThe bacteria can effectively improve reproductive dysfunction in mice induced by a high-fat diet, specifically alleviating reproductive dysfunction in obese mice. Its effects are manifested in increasing testosterone levels, repairing seminiferous epithelial structure, improving sperm quality, and ultimately enhancing embryonic developmental potential. Therefore, this invention isolates and identifies key bacterial strains from an effective intervention model that can directly improve obesity-related sperm quality decline, which is of great significance for the development of novel microecological therapeutic agents. Based on this invention, using... I. valens The preparation of drugs by bacteria for improving spermatogenesis disorders and enhancing sperm quality is of great value for the prevention or adjunctive treatment of male infertility caused by factors such as obesity.

[0066] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A type of *Enterobacter valens* Ileibacterium valens Liu-M1, characterized in that, Its classification name is Enterobacter valens (Valence) Ileibacterium valens (), deposited at the China Center for Type Culture Collection (CCTCC), accession number CCTCC M 20252545.

2. A microbial preparation, characterized in that, Include: a) *Enterobacter valerian* as described in claim 1 Ileibacterium valens Liu-M1, or its bacterial culture, or its metabolites; and b) pharmaceutically or food-grade acceptable carriers.

3. The microbial preparation as described in claim 2, characterized in that, The microbial preparation is a preparation of live bacteria, including *Enterobacter valerian* as described in claim 1. Ileibacterium valens Liu-M1.

4. The microbial preparation as described in claim 2, characterized in that, The formulation may be in the form of capsules, tablets, powders, or liquids.

5. The *Enterobacter valerian* as described in claim 1 Ileibacterium valens The use of Liu-M1 or the microbial preparation as described in any one of claims 2-4 in the preparation of a medicament for improving obesity-related sperm quality decline.

6. The application as described in claim 5, characterized in that, The Valens ileum bacteria Ileibacterium valens Liu-M1, or its bacterial culture, or its metabolites have at least one of the following effects: a) Increase sperm concentration; b) Improve sperm motility, wherein improving sperm motility includes at least one of increasing the percentage of progressively motile sperm or increasing the percentage of total motile sperm; c) Reduce sperm abnormality rate; d) Improve embryonic developmental potential; e) Improve the structure of the seminiferous tubules in the testes; f) Increase the number of spermatogenic cells and / or supporting cells; g) Increase serum testosterone levels.

7. The application as described in claim 6, characterized in that, The spermatogenic cells include DAZL + Cells, SYCP3 + Cells and TNP1 + One or more in the cell; The supporting cell is WT1. + cell.

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