Human microbiota play bei important role in the health of their human being hosts. Recent studies oase demonstrated the microbiota exist in seminal plasma. Die current research aims kommen sie elucidate whether seminal microbiota exist in patients with various types des dysspermatism and whether bacterial biomarkers tun können be identified weil das them. A total of 159 research participants to be recruited, consisting of 22 patients through oligoasthenospermia, 58 patients with asthenospermia, 8 patients with azoospermia, 13 patients through oligospermia, and 58 matched healthy controls. Seminal microbiota composition was analyzed making use of 16S rRNA gene-based sequencing. Ns results confirmed that die composition of seminal microbiota of patients with dysspermatism differed native those of gesund controls. Comparison von the microbiota composition bei semen samples from patients with various types des dysspermatism verified that microbiota in patients v asthenospermia and oligoasthenospermia were distinct from healthy controls bei beta diversity (P Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus and Acinetobacter lwoffii, to be identified based on LEfSe analysis. Inferred functional evaluation based top top seminal microbiome data further indicated die presence von potential pathogenic biomarkers in patients through asthenospermia and oligoasthenospermia. This results provided profiles des seminal microbiota exhibited in different types von dysspermatism, thus providing neu insights right into their pathogenesis.

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Human microbiota, with its diverse relationships—commensal, parasitic, mutualistic, und pathogenic—play in important role in human health. Recent studies have reported the microbiota exist in almost every part of human body—even in the endocrine niche, together as in tumors, blood, and synovial fluid1,2,3,4. Advances an technology und new research oase demonstrated that microbiota room found an seminal plasma, und play bei important role in host homeostasis5. It has actually been prove that ns presence des bacteria in sperm is verbunden with male infertility6. Some bacteria in the urogenital tract may influence spermatogenesis and decrease sperm quality through miscellaneous means, including decrease bei sperm motility, deficiency in DNA integrity, and destruction von mitochondrial function7. Escherichia coli, Mycoplasma genitalium, Ureaplasma urealyticum, Mycoplasma hominis, Staphylococcus aureus, und Chlamydia trachomatis space pathogens associated with male infertility8,9,10,11,12. Several lernen using high-throughput sequencing oase demonstrated that seminal plasma has a bacterial community, which has Lactobacillus, Pseudomonas, Prevotella, and Gardnerella, among others13,14,15,16,17,18,19.

Approximately 15% des couples worldwide are unable kommen sie conceive due zu infertility and males contribute zu 50% von the infertility cases20,21. There are number of causative factors zum male infertility, consisting of genetic und environmental factors21,22,23,24. Sperrdo semen (dysspermatism) is a reason weil das infertility, which occurs an about 50% des the cases of male infertity25,26. Die changes an semen microenvironment might affect die spermatogenesis and motility. Numerous substances have recently been found bei the seminal plasma that impact fertility, such together proteins, metabolites, environmental metals, etc. Contrasted to gesund controls, caspase-3 und cytochrome samen levels to be higher, and the total antioxidant volume (TAC) was lower bei seminal plasma von infertile patients27,28. Testosterone und androstenedione vectors correlate through steroids, i m sorry may function as biomarkers in patients through endocrine disorders, therefore indicating the they may play bei important role bei sexual maturity29. A study deshalb found the follicle-stimulating hormone deficiency could affect male fertility30. Several forschung focused on umwelt chemical substances, consisting of perfluoroalkyl compounds, Pb, Cd, Ba, and U, oase demonstrated the these substances may adversely impact seminal quality31,32,33. To summarize, seminal plasma functions not only together a medium kommen sie carry, protect, und nourish sperm after ~ ejaculation up kommen sie fertilization, but deshalb modulates sperm functions34.

It zu sein critical to identify die bacterial species composition of the microbiota in seminal plasma kommen sie better understand die etiology und pathogenesis des urogenital tract infections and their kombination with infertility. A research that recruited 58 patients v infertility and 19 stark controls observed bacteria an seminal plasma über gram staining und explored die composition von microbiota. However, ns authors did not discover any kind of differences bei the microbiota bei seminal plasma des patients with infertility und healthy controls13. One more study confirmed that human testes have microbiota associated with idiopathic non-obstructive azoospermia15. Javurek et al. Demonstrated the there ist a difference in the composition von seminal microbiota in estrogen receptor-alpha knockout male mice and mice through high-fat diet, which suggests that seminal microbiota might be affected von genetic und environmental factors, thus increasing die risk des disease to ns offspring16,17. These studien focused on the microbiota in seminal plasma, yet did notfall find differences between patients through dysspermatism und healthy controls, hence, they remain inconclusive13,14,15,19,35.

Although vault studies schutz found microbiota in the seminal plasma of males v infertility, it continues to be unknown whether characteristic seminal microbiota exist an patients with various types des dysspermatism. This study aspires to improve ns understanding von seminal microbiota und explore ns potential role von microorganisms, by analyzing die seminal plasma indigenous 159 examine participants and characterizing die microbiota profile. KEGG analysis was adopted zu predict potential pathways relevant with dysspermatism.

To characterize die features des seminal microbiota, 16S rRNA gene sequencing was done zu measure 159 seminal samples, from 22 patients with oligoasthenospermia, 58 patients v asthenospermia, 8 patients through azoospermia, 13 patients with oligospermia, und 58 stark controls. Die clinical characteristics von the examine participants are summarized an Table 1. After pre-processing des sequencing data, we obtained 3,871,353 high-quality sequences (Phred ≥ Q30) with in average von 24,348 von sample, yielding 1,065 taxa weist a 97% identification cut-off. Five leading phyla to be Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes and Fusobacteria, together shown in Fig. 1.

Table 1 Characteristics von individuals investigated an this study.
Full dimension table
Figure 1


Relative abundance des taxa among five groups. Comparison des OTUs and relative taxa abundance amongst asthenospermia, oligospermia, oligoasthenospermia, azoospermia, und healthy controls. (A) weist phylum level; (B) hinweisen genus level.

Altered seminal microbiota an patients with dysspermatism

The aim von the analysis von seminal microbiota was to better understand the differences an seminal microbiota between patients with dysspermatism und healthy controls. Back α diversity consisting of ACE index (P > 0.05) und Shannon index (P > 0.05) confirmed no significant difference an patients v dysspermatism und the healthy control gruppe (Fig. 2A,B), β diversity (based on ns unweighted und weighted UniFrac distance) was significantly different betwee the two groups (r = 0.598, P = 0.001 weighted UniFrac; r = 0.972, P = 0.001, unweighted UniFrac, Fig. 3A,B). A total von 110 considerably different taxa to be detected in the 2 groups. Seminal microbiota an the dysspermatism group was characterized by dominance of genera of Lactobacillus, Bacteroides, Delftia, Sneathia, Enhydrobacter, Anaerococcus, Mycoplana, Finegoldia, Stenotrophomonas, Methylobacterium, Coprobacillus, Aerococcus, Atopobium, Chryseobacterium, Kocuria, Megasphaera, Ralstonia, Achromobacter, Erwinia, Ureaplasma, und Filifactor, and species des Prevotella copri, Saccharopolyspora hirsuta, Kocuria palustris, Prevotella nigrescens, Porphyromonas endodontalis, Lactobacillus coleohominis, Bacteroides barnesiae, und Lactobacillus iners. On die other hand, die microbiota in the stark control gruppe was dominated von genera des Pelomonas, Propionibacterium, Bosea genosp, Bosea, Afipia, Sphingomonas, Vogesella, Brevibacillus, Xylanimicrobium, Flexispira, Pedomicrobium, Phyllobacterium, Aquimonas, Dietzia, Sediminibacterium, Mycobacterium, and Eikenella, and species von Brevibacterium aureum, Propionibacterium acnes, Corynebacterium simulans, Eubacterium dolichum, and Bacillus thermoamylovorans (P 4 and S1A). An summary, we discovered that die composition des seminal microbiota was different between the two groups.


Comparison des alpha diversity und relative abundance punkt phylum level based on the OTUs profile. Boxen plots depict differences an microbiome diversity based upon (A) Shannon index and (B) ACE index between patients through dysspermatism and healthy controls. (C,D) nur Shannon index and ACE index among patients with asthenospermia, oligospermia, oligoasthenospermia, und azoospermia, and healthy controls. Die p value was calculated using ns Wilcoxon rank-sum test.


PCoA analysis des microbiota betwee patients with dysspermatism and healthy controls. (A) Unweighted unifrac PCoA; (B) weighted unifrac PCoA. PCoA analysis of the microbiota among patients v asthenospermia, oligospermia, oligoasthenospermia, und azoospermia, und healthy controls; (C) Unweighted unifrac PCoA; (D) load unifrac PCoA.


The many differentially abundant taxa between patients v dysspermatism und healthy controls (LDA score above 3) created using LEfSe analysis.

Patients v asthenospermia or oligoasthenospermia harbor bei altered seminal microbiota compared to gesund controls

There are differences in the certain pathogenesis von different types des dysspermatism. Zu determine the role of seminal microbiota in the different types des dysspermatism, us analyzed ns seminal microbiota an patients with four different types of dysspermatism—asthenospermia, oligospermia, oligoasthenospermia, und azoospermia, and compared to gesund controls. There was no far-ranging difference in α diversity (Shannon index and ACE index) among die five teams (P > 0.05, Fig. 2C,D). Analysis von β diversity verified seminal microbiota von patients v oligospermia (r = 0.180, P = 0.044, load UniFrac; r = 0.105, P = 0.110, unweighted UniFrac) or azoospermia (r = 0.207, P = 0.073, weighted UniFrac; r = 0.169, P = 0.096, unweighted UniFrac) showed no significant difference wie compared kommen sie that of stark controls; vice versa, seminal microbiota in patients with asthenospermia (r = 0.294, P = 0.0001, load UniFrac; r = 0.362, P = 0.0001, unweighted UniFrac) or oligoasthenospermia (r = 0.270, P = 0.001, weighted UniFrac; r = 0.316, P = 0.001, unweighted UniFrac) had far-reaching composition sport compared zu that of healthy controls (Fig. 3C,D).

Patients v asthenospermia harbored distinctive bacterial biomarkers, which may oase potential pathogenicity

LEfSe evaluation (Linear discriminant analysis Effect Size) was used zu explore ns bacterial biomarkers in the semen of patients through asthenospermia. Eighty various taxa in the two teams were chosen based upon LDA > 2. Far-ranging increase in the family member abundance of Sneathia, Ralstonia, Ureaplasma, Bacteroides, Chryseobacterium, Aerococcus, Enhydrobacter, Methylobacterium, Anaerococcus, Stenotrophomonas, Mycoplana, Delftia, Finegoldia, Corynebacterium, und Lactobacillus (at the genus level) and Saccharopolyspora hirsute, Acinetobacter lwoffii, and Lactobacillus iners (at ns species level) was observed, and a significant reduction bei Pelomonas, Propionibacterium, Bosea, Sphingomonas, Phyllobacterium, Pedomicrobium, Xylanimicrobium, Mycobacterium, and Zoogloea (at the genus level) and Propionibacterium acnes and Bosea genosp (at ns species level) was observed in the asthenospermia group, compared kommen sie the healthy control gruppe (Figs. 5A,B and S1B).

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LEfSe analysis bolzen patients asthenospermia and healthy controls. (A,B) Comparison of the many differentially abundant taxa bolzen patients with asthenospermia und healthy controls (LDA score over 3) created using LEfSe analysis. Us selected 4 biomarkers kommen sie predict the probability von patients v asthenospermia. (CF) these biomarkers are Propionibacterium, Pelomonas, Lactobacillus, and Propionibacterium acnes. The ROC curves also as die AUC (Area Under die Curve) worths were calculated using SPSS.

To evaluate die potential value of the identified bacterial biomarkers weil das asthenospermia, ROC curves und AUC values were computed. The criteria used zum biomarkers are—the genus and species von LDA > 3. 4 biomarkers including Propionibacterium (ROC-plot AUC value was 0.650, 95% to trust interval : 54.6–75.3%), Pelomonas (ROC-plot AUC value was 0.683, 95% CI: 58.4–78.2%), Lactobacillus (ROC-plot AUC value was 0.841, 95% CI: 76.2–92.0%), und Propionibacterium acnes (ROC-plot AUC value was 0.647, 95% CI: 54.4–75.1%) were filtered. Additionally, us evaluated the effects von age und pH von seminal plasma on ns four candidate biomarkers, an patients v asthenospermia and those in healthy controls (Fig. 5C–F). None von these factors had significant effect on die selected candidate biomarkers (Table S1).

Unique pathogenic bacteria bei patients v oligoasthenospermia

In order kommen sie select ns biomarkers bei oligoasthenospermia und healthy controls, we offered LEfSe to analyze the composition von seminal microbiota in both groups. Seminal microbiota bei the oligoasthenospermia gruppe were characterized von a dominance des Ralstonia, Oscillospira, Parabacteroides, Lachnospira, Phascolarctobacterium, Chryseobacterium, Zoogloea, Ruminococcus, Stenotrophomonas, Actinoplanes, Mycoplana, Delftia, Sneathia, Megasphaera, Atopobium, Faecalibacterium, Bacteroides, Lactobacillus, Bacteroides uniformis, Stenotrophomonas panacihumi, Bacteroides plebeius, Prevotella copri, and Faecalibacterium prausnitzii, whereas microbiota bei healthy controls were dominated von Acinetobacter, Propionibacterium, Pelomonas, Bosea, Deinococcus, Sphingomonas, Sediminibacterium, Pseudomonas, Pedomicrobium, Acinetobacter johnsonii, Streptococcus anginosus, Propionibacterium acnes, und Bosea genosp (Figs. 6A,B und S1C).

LEfSe analysis between patients v oligoasthenospermia und healthy controls. (A,B) Comparison of the most differentially abundant taxa betwee patients with oligoasthenospermia and healthy controls (LDA score over 3), were created using LEfSe analysis. (CH) these biomarkers space Lactobacillus, Acinetobacter, Propionibacterium, Pelomonas, Prevotella copri, and Propionibacterium acnes. Die ROC curves too as the AUC (Area Under ns Curve) value was calculated making use of SPSS.

As previously described, 6 biomarkers were selected in patients v oligoasthenospermia und healthy controls, which had Lactobacillus (ROC-plot AUC value was 0.773, 95% CI: 66.2–88.4%), Acinetobacter (ROC-plot AUC value was 0.679, 95% CI: 54.5–81.3%), Propionibacterium (ROC-plot AUC value was 0.727, 95% CI: 61.3–84.1%), Pelomonas (ROC-plot AUC value was 0.662, 95% CI: 52.9–79.6%), Prevotella copri (ROC-plot AUC value was 0.763, 95% CI: 63.2–89.3%), and Propionibacterium acnes (ROC-plot AUC value was 0.724, 95% CI: 61.0–83.9%) (Fig. 6C–H). We deshalb evaluated this candidate biomarkers von using confounding factors and found that there to be no confounding determinants that could affect these biomarkers (Table S2).

Predicted metagenome functions bei patients with asthenospermia und healthy controls, and patients v oligoasthenospermia und healthy controls

Phylogenetic investigation of Communities von Reconstruction des Unobserved says (PICRUSt) was used zu predict ns different KEGG pathways in the two groups, und to comment on potential mechanisms des seminal microbiota in asthenospermia and oligoasthenospermia groups. Forty various KEGG pathways were displayed bei patients through asthenospermia; these exhibited increased activities an some condition pathways such together cell growth und death, lipid metabolism, enzyme families, transmittable diseases, cell division, cell motility, etc. There room 32 different KEGG pathways in patients through oligoasthenospermia und healthy controls, i beg your pardon showed boosted pathways in cell growth und death, lipid metabolism, and metabolic diseases in patients with oligoasthenospermia (Fig. 7).

Predicted metagenome function based on KEGG pathway analysis. Expanded error gittern plot showed substantially different KEGG pathways between (A) patients v asthenospermia und healthy controls; (B) betwee patients v oligoasthenospermia and healthy controls.

In this study, high-throughput sequencing technology was used to analyze und measure ns microbiota found in seminal plasma. Our research demonstrated the patients with various types von dysspermatism (oligoasthenospermia or asthenospermia) had considerably different composition of microbiota wie compared to stark controls. This pilot study deshalb explored die opportunistic pathogens bei the seminal plasma, which could be potential pathogens that increase the risk von dysspermatism.

Technological advances in recent year have led to several forschung on ns relationship between microbiota and human health. A large number von studies oase shown that disorders of human microbial groups tun können lead zu diseases, such together type ii diabetes36. Current studies have shown that bacteria so exist bei the synovial fluid des patients with arthritis und play an important role an the occurrence des arthritis3. More interestingly, there room microorganisms an the blood4. This evidence indicates that different niches des the person body atmosphere harbor distinct und potentially practical microbiota. In recent years, high throughput sequencing has been used to measure bacteria in seminal plasma, by which Lactobacillus, Pseudomonas, Prevotella Streptococcus, und Gardnerella were revealed to exist in seminal samples of patients and healthy controls13,14,15,19,35. This studies also found potentially pathogenic bacteria, such together Finegoldia and Anaerococcus13,14. We analyzed ns composition of microbiota in the seminal plasma at the phylum level und found five dominant phyla: Proteobacteria, Firmicutes, Actinobacteria, Bacteroidetes, und Fusobacteria, which ist consistent with the findings des a previous study15. We deshalb analyzed major genera in the seminal plasma. Ns top 10 relatively abundant genera discovered commonly an the male seminal plasma were: Lactobacillus, Corynebacterium, Acinetobacter, Prevotella, Enterococcus, Veillonella, Streptococcus, Porphyromonas, Sneathia, and Pelomonas37. Based on all current studies, microbiota exist in the seminal plasma und share similar microbial community composition13,14,15,16,17,18,35.

Variation in the composition von microbiota could impact patients with asthenospermia or oligoasthenospermia. We uncovered most des the taxa that were found in increased concentration an the seminal fluid des patients through asthenospermia und oligoasthenospermia to be gram-negative bacteria include lipopolysaccharide (LPS) in their cabinet walls. LPS can upregulate cytokines causing inflammation38. A previous study indicated that inflammation mediators kann sein directly cause DNA fragmentation in ejaculated spermatozoa, which eventually limits ns fertilization abilities von the germ cells39.

The relative abundance of Ureaplasma, Bacteroides, Anaerococcus, Finegoldia, Lactobacillus, und Acinetobacter lwoffii was significantly higher in asthenospermia, und Lactobacillus was notably abundant an oligoasthenospermia. Ureaplasma is the smallest prokaryote bolzen bacteria and viruses, largely found an the genitourinary tract des the human being body. Bacteroides ureolyticus is a species des Bacteroides that could impair sperm structure und function von diminishing motility und causing sperm membrane injury, particularly to die lipid bilayers as shown an in vitro tests29,40,41. One more study using 16S rRNA sequencing demonstrated that genus Anaerococcus can be a biomarker zum predicting male infertility13. We so found this bacterium an patients v asthenospermia. Lactobacillus zu sein a gram-positive bacterium, i beg your pardon produces SCFA (short-chain fat acids). Recent studies schutz shown the SCFA room beneficial kommen sie human health. However, seminal pH ist generally 7.242. Significant increase von Lactobacillus in asthenospermia might change the pH von semen und result in male infertility. Although our results uncovered Lactobacillus in human semen, ns mechanism remains to be determined, however, the provides new insights right into male infertility.

Bacteria the were filtered out von factors such as age may be potentially pathogenic. The characteristic des asthenospermia ist that the activity von spermatozoa is weakened. Us found in increase an Lactobacillus and decrease in Propionibacterium, Pelomonas, and Propionibacterium acnes an the seminal plasma des patients with asthenospermia, which indicated that these bacteria may affect sperm activity. Oligoasthenospermia attributes both lesser and weaker sperm activity. Our results indicated an increase in Lactobacillus and Prevotella copri und decrease in Propionibacterium, Pelomonas, Acinetobacter, und Propionibacterium acnes, which may correlate with sperm formation und activity.

PICRUSt was used to predict potential metabolic pathways. We found that the lipid metabolism was significantly different bei the three speculative groups. Die essence of geschlecht hormones is steroids. Previous studies schutz demonstrated that obstacle of geschlecht hormones result bei male infertility. Zum instance, changes an FSH, LH, and T level are damit verbundenen with damage to the testes, impeding von spermatogenesis and maturation, and result bei decreased sperm motility and activity, leading zu infertility43,44,45. This finding deshalb exhibits strong correlation with die change an microbiota.

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To summarize, ours results imply that dysspermatism is relevant with seminal microbiota, and deshalb show that seminal microbiota in patients through asthenospermia and oligoasthenospermia are different from those bei healthy controls. Biomarkers to be screened and the KEGG metabolic pathways predicted. These results are beneficial for clinical diagnosis and could be additional used to develop neu treatment zum patients v dysspermatism. Although us performed a bacter culture experiment on semen samples, die pathogens were not cultured because von their low content. Kommen sie better understand die mechanism of dysspermatism, future forschung are needed bei combination v metabolomics und culturomics.