Endometrial Microbiome and Women’s Reproductive Health – Review of the Problem Endometrial Microbiome and Reproductive Health

Currently, unlike in the past, the endometrial cavity is not considered to be sterile. The endometrium is supposed to be dominated by Lactobacilli, but also their deficiency can be found in the reproductive tract of asymptomatic healthy women. Sometimes the endometrial microbiome is dominated by various pathological microorganisms, and this can lead to various conditions as chronic endometritis, chorioamnionitis and preterm birth. Their presence causes uterine inflammation and infection, release of pro-inflammatory molecules, uterine contractions, disruption of cervical barrier, premature rupture of membranes. Uterine dysbiosis is associated with recurrent implantation failure and recurrent miscarriages. As the microbiome is important for maintaining immunological homeostasis at the level of gastrointestinal tract Lactobacilli may play a similar function at the level of uterus. The lactobacillus-dominated uterine microbiome is of great importance for maintaining a hostile uterine microenvironment, embryo implantation, early pregnancy development and normal pregnancy outcome.

Gut Microbiota-Modulated Metabolomic Profiling Shapes the Etiology and Pathogenesis of Autoimmune Diseases

Autoimmunity is a complex and multifaceted process that contributes to widespread functional decline that affects multiple organs and tissues. The pandemic of autoimmune diseases, which are a global health concern, augments in both the prevalence and incidence of autoimmune diseases, including type 1 diabetes, multiple sclerosis, and rheumatoid arthritis. The development of autoimmune diseases is phenotypically associated with gut microbiota-modulated features at the molecular and cellular levels. The etiology and pathogenesis of autoimmune diseases comprise the alterations of immune systems with the innate and adaptive immune cell infiltration into specific organs and the augmented production of proinflammatory cytokines stimulated by commensal microbiota. However, the relative importance and mechanistic interrelationships between the gut microbial community and the immune system during progression of autoimmune diseases are still not well understood. In this review, we describe studies on the profiling of gut microbial signatures for the modulation of immunological homeostasis in multiple inflammatory diseases, elucidate their critical roles in the etiology and pathogenesis of autoimmune diseases, and discuss the implications of these findings for these disorders. Targeting intestinal microbiome and its metabolomic associations with the phenotype of autoimmunity will enable the progress of developing new therapeutic strategies to counteract microorganism-related immune dysfunction in these autoimmune diseases.

Contribution of the Commensal Microflora to the Immunological Homeostasis and the Importance of Immune-Related Drug Development for Clinical Applications

Not long ago, self-reactive immune activity was considered as pathological trait. A paradigm shift has now led to the recognition of autoimmune processes as part of natural maintenance of molecular homeostasis. The immune system is assigned further roles beneath the defense against pathogenic organisms. Regarding the humoral immune system, the investigation of natural autoantibodies that are frequently found in healthy individuals has led to further hypotheses involving natural autoimmunity in other processes as the clearing of cellular debris or decrease in inflammatory processes. However, their role and origin have not been entirely clarified, but accumulating evidence links their formation to immune reactions against the gut microbiome. Antibodies targeting highly conserved proteins of the commensal microflora are suggested to show self-reactive properties, following the paradigm of the molecular mimicry. Here, we discuss recent findings, which demonstrate potential links of the commensal microflora to the immunological homeostasis and highlight the possible implications for various diseases. Furthermore, specific components of the immune system, especially antibodies, have become a focus of attention for the medical management of various diseases and provide attractive treatment options in the future. Nevertheless, the development and optimization of such macromolecules still represents a very time-consuming task, shifting the need to more medical agents with simple structural properties and low manufacturing costs. Synthesizing only the biologically active sites of antibodies has become of great interest for the pharmaceutical industry and offers a wide range of therapeutic application areas as it will be discussed in the present review article.

Peculiarities of genital tract microbiocenosis and immunological homeostasis in reproductive-age women with uterine leiomyoma

The objective: To determine the features of the microbiocenosis of the genital tract and immunological homeostasis and in women of reproductive age with uterine leiomyoma.Materials and methods. The microbiocenosis of the genital tract and immunological homeostasis of 308 women with uterine leiomyoma aged 23–49 years were studied. The control group included 30 healthy women aged 24–37 years. Results. In women of reproductive age, the development of uterine leiomyoma is associated with a significant violation of the microecology of the genitals, the presence of nonspecific vaginitis and bacterial vaginosis, increased frequency and concentration of pathogenic flora (staphylococci and streptococci with hemolytic properties, enterobacteria), STIs or reducing the concentration of protective microflora.The study of the peculiarities of the functioning of the immune system at the local level in the presence of uterine leiomyoma indicates unidirectional disorders in the state of local immunity and changes in the protective function of cervical mucus in the examined women. Thus, under conditions of uterine leiomyoma, there is a significant activation of local immunological factors, as evidenced by a significant increase in the concentration of IgG, IgA and the appearance of IgM in cervical mucus in 27,5–32,5 % of women with uterine leiomyoma. In addition, there was suppression of phagocytic activity of neutrophils, which was manifested by a significant decrease in activity and intensity of phagocytosis, with a decrease in their functional reserve by NRT test, which creates conditions for intracellular persistence of infection, activation and persistence of inflammatory progression.Conclusions. The obtained data indicate a violation of the microecology of the genitals and the intensity of immunogenesis in women with uterine leiomyoma, which indicates that the inflammatory process of the genitals is one of the significant factors that lead to the emergence and progression of uterine leiomyoma.

P688 Association of Akkermansia muciniphila with a healthy gut microbiome

Background Comprehensive knowledge of the types and ratios of microbes present in the healthy gastrointestinal human gut is required before any study is attempted to alter the microbiome to treat one condition. Akkermansia muciniphila, a mucin-degrading bacterium, belonging to the phylum Verrucomicrobia, has been inversely associated with inflammation and diabetes whilst it has been internationally proposed as one of the contributors for maintaining a healthy gut and glucose homeostasis. Studies noted that higher amounts of this microorganism in the gut microbiota was linked to a metabolically healthier lifestyle; therefore, linking an interaction between the gut bacterial richness and abundance of A. muciniphila. This organism was noted to improve the gut barrier using its outer membrane protein Amuc 1100, which seems to interact with Toll-like receptor 2, whilst potentially adhering to intestinal epithelial cells, leading its role in balancing the human immunological homeostasis whilst strengthening the monolayer integrity of the wall. The aim of this study was to assess if there is any difference in the presence of Akkermansia muciniphila between IBD patients and controls. Methods Faecal microbiota from newly diagnosed treatment naïve IBD patients and controls were analysed via the bacterial 16s rRNA gene sequencing on illumine MiSeq. Results 100 patients with IBD and 97 controls were recruited. Forty-one different ASVs were identified from our cohort, all of which being differentially abundant between the different health conditions present. From these, 20 ASVs such as ASV-14 G-Alistipes uncl., and ASV 20-Akkermansia muciniphila, were found to be more abundant in healthy individuals than in IBD patients. There was no dietary association. Conclusion In this study Akkermansia muciniphila was significantly found in higher amount in the healthy control population than in the IBD cohort. The potential role of repopulating the gut bacteria with Akkermansia muciniphila needs to be investigated as to reduce the burden of disease, medications prescribed and the clinical outcome.

Cellular immunity indexes after therapeutic use of immunoactive and anti-inflammatory agents in patients with orthodontically induced gingival hyperplasia

Orthodontic treatment with fixed appliances that is mediated by the power forces of the apparatus might lead to changes in the blood circulation, predispose to a number of complications such as tooth movement and contributes to the morphological bone tissue remodeling. We have investigated 126 patients aged 16–35 years after appliance bracket therapy that has caused orthodontically induced gingival hyperplasia. Immunological investigation which comprised the study of the cellular immune system in patients with orthodontically induced gingival hyperplasia suggested that there were significant disorders of the cellular immune system that correspond to the T-suppressor type of the secondary immunodeficiency state. Endogenous interferon composed of a low molecular weight organic compounds and an interferon-inducing agent (isonicotinic acid derivative) was used in the treatment of the patients with orthodontically induced gingival hyperplasia. Interferon provides restoration of functional activity in T-lymphocytes, enhances the functional capacity of the macrophages, provides normalization of the cell immunity, contributes to the elimination of secondary immunodeficiency and restoration of immunological homeostasis in individuals with orthodontically induced gingival hyperplasia caused by fixed appliances.

Detection of Pathogens and Regulation of Immunity by the Caenorhabditis elegans Nervous System

ABSTRACT Although Caenorhabditis elegans has been used as a model host for studying host-pathogen interactions for more than 20 years, the mechanisms by which it identifies pathogens are not well understood. This is largely due to its lack of most known pattern recognition receptors (PRRs) that recognize pathogen-derived molecules. Recent behavioral research in C. elegans indicates that its nervous system plays a major role in microbe sensing. With the increasing integration of neurobiology in immunological research, future studies may find that neuronal detection of pathogens is an integral part of C. elegans-pathogen interactions. Similar to that of mammals, the C. elegans nervous system regulates its immune system to maintain immunological homeostasis. Studies in the nematode have revealed unprecedented details regarding the molecules, cells, and signaling pathways involved in neural regulation of immunity. Notably, some of the studies indicate that some neuroimmune regulatory circuits need not be “activated” by pathogen infection because they are tonically active and that there could be a predetermined set point for internal immunity, around which the nervous system adjusts immune responses to internal or external environmental changes. Here, we review recent progress on the roles of the C. elegans nervous system in pathogen detection and immune regulation. Because of its advantageous characteristics, we expect that the C. elegans model will be critical for deciphering complex neuroimmune signaling mechanisms that integrate and process multiple sensory cues.

The Hygiene Hypothesis – Learning From but Not Living in the Past

Postulated by Strachan more than 30 years ago, the Hygiene Hypothesis has undergone many revisions and adaptations. This review journeys back to the beginnings of the Hygiene Hypothesis and describes the most important landmarks in its development considering the many aspects that have refined and generalized the Hygiene Hypothesis over time. From an epidemiological perspective, the Hygiene Hypothesis advanced to a comprehensive concept expanding beyond the initial focus on allergies. The Hygiene Hypothesis comprise immunological, microbiological and evolutionary aspects. Thus, the original postulate developed into a holistic model that explains the impact of post-modern life-style on humans, who initially evolved in close proximity to a more natural environment. Focusing on diet and the microbiome as the most prominent exogenous influences we describe these discrepancies and the resulting health outcomes and point to potential solutions to reestablish the immunological homeostasis that frequently have been lost in people living in developed societies.