Intestinal microbiota is an element of the bacterial ecosystem in all mammalian organisms. These microorganisms play a very important part in the development, functioning, and modulation of the immune system from the moment of birth. In recent years, owing to the use of modern sequencing techniques, the microbiome composition in healthy people has been identified based on bacterial 16S rRNA analysis. Currently, more and more attention is being given to the influence of microorganisms on the host’s cellular metabolism. Analysis of microbial metabolites, among them short-chain fatty acids (SCFAs), and disruption of intestinal microbiota homeostasis in terms of their effects on molecular regulatory mechanisms of immune reactions will surely improve the understanding of the etiology of many common diseases. SCFAs, mainly butyrate, propionate, and acetate, occur in specific amounts, and their proportions can change, depending on the diet, age and diseases. The levels of SCFAs are substantially influenced by the ratio of commensal intestinal bacteria, the disturbance of which (dysbiosis) can lead to a disproportion between the SCFAs produced. SCFAs are regarded as mediators in the communication between the intestinal microbiome and the immune system. The signal they produce is transferred, among others, in immune cells via free fatty acid receptors (FFARs), which belong to the family of G protein-coupled receptors (GPCRs). It has been also confirmed that SCFAs inhibit the activity of histone deacetylase (HDAC) – an enzyme involved in post-translational modifications, namely the process of deacetylation and, what is new, the process of histone crotonylation. These properties of SCFAs have an effect on their immunomodulatory potential i.e. maintaining the anti/pro-inflammatory balance. SCFAs act not only locally in the intestines colonized by commensal bacteria, but also influence the intestinal immune cells, and modulate immune response by multi-protein inflammasome complexes. SCFAs have been confirmed to contribute to the maintenance of the immune homeostasis of the urinary system (kidneys), respiratory system (lungs), central nervous system, and the sight organ.

Gut microbiome-derived short-chain fatty acids (SCFAs) emerge in the process of fermentation of polysaccharides that resist digestion (dietary fiber, resistant starch). SCFAs have a very high immunomodulatory potential and ensure local homeostasis of the intestinal epithelium, which helps maintain the intestinal barrier. We analyzed the association between stool SCFAs levels acetic acid (C 2:0), propionic acid (C 3:0), isobutyric acid (C 4:0i), butyric acid (C 4:0n), isovaleric acid (C 5:0i) valeric acid (C 5:0n), isocaproic acid (C 6:0i), and caproic acid (C 6:0n)) in aging man with benign prostatic hyperplasia (BPH) and healthy controls. The study involved 183 men (with BPH, n = 103; healthy controls, n = 80). We assessed the content of SCFAs in the stool samples of the study participants using gas chromatography. The levels of branched SCFAs (branched-chain fatty acids, BCFAs): isobutyric acid (C4:0i) (p = 0.008) and isovaleric acid (C5:0i) (p < 0.001) were significantly higher in patients with BPH than in the control group. In healthy participants isocaproic acid (C6:0i) predominated (p = 0.038). We also analyzed the relationship between stool SCFA levels and serum diagnostic parameters for MetS. We noticed a relationship between C3:0 and serum lipid parameters (mainly triglycerides) in both healthy individuals and patients with BPH with regard to MetS. Moreover we noticed relationship between C4:0i, C5:0i and C6:0i and MetS in both groups. Our research results suggest that metabolites of the intestinal microflora (SCFAs) may indicate the proper function of the intestines in aging men, and increased BCFAs levels are associated with the presence of BPH.

Human leukocyte antigen G (HLA-G) is observed in immune system cells and other organs. It is a class Ib molecule, which plays a pivotal role in the implantation and maintenance of pregnancy. The aim of this study was to assess the relationship between serum sHLA-G levels and the HLA-G allele in parental pairs with complicated obstetric histories. The clinical material consisted of 210 women and 190 men with the experience of a complicated or an unsuccessful pregnancy. The control group included parents―89 women and 86 men―lacking complicated obstetric histories. We applied genetic analysis methods: isolation of genomic DNA, sequencing, and determination of serum sHLA-G levels. There were no statistically significant differences in the frequencies of the HLA-G −725 C>G polymorphism between particular experimental groups compared with the control group (p > 0.05). The median sHLA-G levels in the women with the HLA-G10101 allele (15.4 U/mL) were significantly higher than in the women with other alleles (p < 0.05). The HLA-G 10101 allele seems to protect against antiphospholipid syndrome, which may be associated with increased serum sHLA-G levels in its carriers. The relationship between serum sHLA-G levels and the HLA-G polymorphisms in the Polish population requires further investigation.

The understanding of the molecular and biochemical characteristics of the human leukocyte antigen-G (HLA-G) is important because of the diverse influence of this antigen’s polymorphisms on the course of a pregnancy. The aim of our study was to assess how the variation of the HLA-G allele and the HLA-G 14-bp ins/del polymorphism influence predisposition to a complicated pregnancy. The clinical material consisted of parental pairs with complicated pregnancies (210 women; 190 men). The control group included parental pairs without complications during pregnancy (89 women; 86 men). The study involved isolation of genome DNA from peripheral blood leukocytes, sequencing, and analysis of the 14-bp ins/del polymorphism in the 3′-untranslated region (3′-UTR) of the HLA-G gene based on polymerase chain reaction (PCR). The most common HLA-G allele in the group of women with complicated pregnancies was the HLA-G 10101 allele. There were no statistically significant differences in the frequencies of the 14-bp ins/del polymorphism in the 3′UTR of the HLA-G gene between the groups. Our results suggest that the risk of complications in pregnancy is influenced by the HLA-G 10101, HLA-G 10108, and HLA-G 10106 alleles and is not influenced by the 14-bp ins/del polymorphism in the 3′UTR of the HLA-G gene.

Our research was designed to verify the relationship between male infertility, basic semen characteristics (with respect to detailed sperm morphology), sperm DNA fragmentation (SDF), oxidation‒reduction potential in semen (ORP), and leukocytospermia. The obtained results showed that infertile groups (with or without leukocytospermia) had significantly lower basic semen characteristics and higher SDF, raw ORP, and static ORP (sORP) than fertile controls. The thresholds of 13% SDF (AUC = 0.733) and 1.40 sORP (AUC = 0.857) were predictive values for discriminating infertile from fertile men. In infertile groups, a higher prevalence and risk for >13% SDF and >1.40 sORP were revealed. Unexpectedly, leukocytospermic subjects had lower sORP, prevalence, and risk for >1.40 sORP than leukocytospermic-negative men. These groups did not differ in SDF and raw ORP. Both SDF and sORP negatively correlated with basic semen parameters but positively correlated with sperm head and midpiece defects. sORP positively correlated with sperm tail defects, immature sperm cells with excess residual cytoplasm, and SDF. In turn, raw ORP negatively correlated with sperm count but positively correlated with SDF and sORP. These findings indicate that (1) there is a relationship between male infertility, SDF, and OS in semen; (2) in infertile men, there is a clinically significant risk of SDF and OS irrespective of leukocytospermia; and (3) the assessment of SDF and oxidative stress should be independent of leukocytospermia.