The Hidden Relationship between Intestinal Microbiota and Immunological Modifications in Preeclampsia Pathogenesis.

Preeclampsia is a multifactorial gestational syndrome characterized by increased blood pressure during pregnancy associated with multiorgan involvement. The impact of this disease on maternal and neonatal health is significant, as it can lead to various fetal comorbidities and contribute to the development of maternal comorbidities later in life. Consistent evidence has shown that the microbiota acts as a regulator of the immune system, and it may, therefore, influence the development of preeclampsia by modulating immune factors. This narrative review aims to investigate the role of the immune system in the pathogenesis of preeclampsia and to summarize the most recent literature on the possible link between preeclampsia and alterations in the intestinal microbiota. To this end, we conducted a literature search, aiming to perform a narrative review, on PubMed and Embase from January 1990 to March 2024, focusing on the latest studies that highlight the main differences in microbial composition between patients with and without preeclampsia, as well as the effects of microbial metabolites on the immune system. From the review of 28 studies assessing the intestinal microbiota in preeclamptic women, preeclampsia could be associated with a state of dysbiosis. Moreover, these patients showed higher plasmatic levels of endotoxin, pro-inflammatory cytokines, and T helper 17 cells; however, the findings on specific microbes and metabolites that could cause immune imbalances in preeclampsia are still preliminary.

Early Life Adversity, Microbiome, and Inflammatory Responses.

Early life adversity has a profound impact on physical and mental health. Because the central nervous and immune systems are not fully mature at birth and continue to mature during the postnatal period, a bidirectional interaction between the central nervous system and the immune system has been hypothesized, with traumatic stressors during childhood being pivotal in priming individuals for later adult psychopathology. Similarly, the microbiome, which regulates both neurodevelopment and immune function, also matures during childhood, rendering this interaction between the brain and the immune system even more complex. In this review, we provide evidence for the role of the immune response and the microbiome in the deleterious effects of early life adversity, both in humans and rodent models.

Intersection of the microbiome and immune metabolism in lupus.

Systemic lupus erythematosus is a complex autoimmune disease resulting from a dysregulation of the immune system that involves gut dysbiosis and an altered host cellular metabolism. This review highlights novel insights and expands on the interactions between the gut microbiome and the host immune metabolism in lupus. Pathobionts, invasive pathogens, and even commensal microbes, when in dysbiosis, can all trigger and modulate immune responses through metabolic reprogramming. Changes in the microbiota's global composition or individual taxa may trigger a cascade of metabolic changes in immune cells that may, in turn, reprogram their functions. Factors contributing to dysbiosis include changes in intestinal hypoxia, competition for glucose, and limited availability of essential nutrients, such as tryptophan and metal ions, all of which can be driven by host metabolism changes. Conversely, the accumulation of some host metabolites, such as itaconate, succinate, and free fatty acids, could further influence the microbial composition and immune responses. Overall, mounting evidence supports a bidirectional relationship between host immunometabolism and the microbiota in lupus pathogenesis.

Understanding the influence of the microbiome on childhood infections.

INTRODUCTION: The microbiome is known to have a substantial impact on human health and disease. However, the impacts of the microbiome on immune system development, susceptibility to infectious diseases, and vaccine-elicited immune responses are emerging areas of interest. AREAS COVERED: In this review, we provide an overview of development of the microbiome during childhood. We highlight available data suggesting that the microbiome is critical to maturation of the immune system and modifies susceptibility to a variety of infections during childhood and adolescence, including respiratory tract infections, Clostridioides difficile infection, and sexually transmitted infections. We discuss currently available and investigational therapeutics that have the potential to modify the microbiome to prevent or treat infections among children. Finally, we review the accumulating evidence that the gut microbiome influences vaccine-elicited immune responses among children. EXPERT OPINION: Recent advances in sequencing technologies have led to an explosion of studies associating the human microbiome with the risk and severity of infectious diseases. As our knowledge of the extent to which the microbiome influences childhood infections continues to grow, microbiome-based diagnostics and therapeutics will increasingly be incorporated into clinical practice to improve the prevention, diagnosis, and treatment of infectious diseases among children.

Evaluation of the Role of Probiotics As a New Strategy to Eliminate Microbial Toxins: a Review.

Probiotics are living microorganisms that have favorable effects on human and animal health. The most usual types of microorganisms recruited as probiotics are lactic acid bacteria (LAB) and bifidobacteria. To date, numerous utilizations of probiotics have been reported. In this paper, it is suggested that probiotic bacteria can be recruited to remove and degrade different types of toxins such as mycotoxins and algal toxins that damage host tissues and the immune system causing local and systemic infections. These microorganisms can remove toxins by disrupting, changing the permeability of the plasma membrane, producing metabolites, inhibiting the protein translation, hindering the binding to GTP binding proteins to GM1 receptors, or by preventing the interaction between toxins and adhesions. Here, we intend to review the mechanisms that probiotic bacteria use to eliminate and degrade microbial toxins.

What Function Do Platelets Play in Inflammation and Bacterial and Viral Infections?

The article presents the function of platelets in inflammation as well as in bacterial and viral infections, which are the result of their reaction with the endovascular environment, including cells of damaged vascular endothelium and cells of the immune system. This role of platelets is conditioned by biologically active substances present in their granules and in their specific structures - EV (extracellular vesicles).

Term Infant Formulas Influencing Gut Microbiota: An Overview.

Intestinal colonization of the neonate is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding or formula feeding]. Postnatal immune maturation is dependent on the intestinal microbiome implementation and composition and type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function. It is well established that exclusive breastfeeding for 6 months or more has several benefits with respect to formula feeding. The composition of the new generation of infant formulas aims in mimicking HM by reproducing its beneficial effects on intestinal microbiome and on the gut associated immune system (GAIS). Several approaches have been developed currently for designing new infant formulas by the addition of bioactive ingredients such as human milk oligosaccharides (HMOs), probiotics, prebiotics [fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs)], or by obtaining the so-called post-biotics also known as milk fermentation products. The aim of this article is to guide the practitioner in the understanding of these different types of Microbiota Influencing Formulas by listing and summarizing the main concepts and characteristics of these different models of enriched IFs with bioactive ingredients.

Intestinal Microbiota as a Contributor to Chronic Inflammation and Its Potential Modifications.

The gut microbiota is a crucial factor in maintaining homeostasis. The presence of commensal microorganisms leads to the stimulation of the immune system and its maturation. In turn, dysbiosis with an impaired intestinal barrier leads to accelerated contact of microbiota with the host's immune cells. Microbial structural parts, i.e., pathogen-associated molecular patterns (PAMPs), such as flagellin (FLG), peptidoglycan (PGN), lipoteichoic acid (LTA), and lipopolysaccharide (LPS), induce inflammation via activation of pattern recognition receptors. Microbial metabolites can also develop chronic low-grade inflammation, which is the cause of many metabolic diseases. This article aims to systematize information on the influence of microbiota on chronic inflammation and the benefits of microbiota modification through dietary changes, prebiotics, and probiotic intake. Scientific research indicates that the modification of the microbiota in various disease states can reduce inflammation and improve the metabolic profile. However, since there is no pattern for a healthy microbiota, there is no optimal way to modify it. The methods of influencing microbiota should be adapted to the type of dysbiosis. Although there are studies on the microbiota and its effects on inflammation, this subject is still relatively unknown, and more research is needed in this area.

Microbiota in Health and Disease-Potential Clinical Applications.

Within the last two decades tremendous efforts in biomedicine have been undertaken to understand the interplay of commensal bacteria living in and on our human body with our own human physiology. It became clear that (1) a high diversity especially of the microbial communities in the gut are important to preserve health and that (2) certain bacteria via nutrition-microbe-host metabolic axes are beneficially affecting various functions of the host, including metabolic control, energy balance and immune function. While a large set of evidence indicate a special role for small chain fatty acids (SCFA) in that context, recently also metabolites of amino acids (e.g., tryptophan and arginine) moved into scientific attention. Of interest, microbiome alterations are not only important in nutrition associated diseases like obesity and diabetes, but also in many chronic inflammatory, oncological and neurological abnormalities. From a clinician's point of view, it should be mentioned, that the microbiome is not only interesting to develop novel therapies, but also as a modifiable factor to improve efficiency of modern pharmaceutics, e.g., immune-therapeutics in oncology. However, so far, most data rely on animal experiments or human association studies, whereas controlled clinical intervention studies are spare. Hence, the translation of the knowledge of the last decades into clinical routine will be the challenge of microbiome based biomedical research for the next years. This review aims to provide examples for future clinical applications in various entities and to suggest bacterial species and/or microbial effector molecules as potential targets for intervention studies.

Mold, Mycotoxins and a Dysregulated Immune System: A Combination of Concern?

Fungi represent one of the most diverse and abundant eukaryotes on earth. The interplay between mold exposure and the host immune system is still not fully elucidated. Literature research focusing on up-to-date publications is providing a heterogenous picture of evidence and opinions regarding the role of mold and mycotoxins in the development of immune diseases. While the induction of allergic immune responses by molds is generally acknowledged, other direct health effects like the toxic mold syndrome are controversially discussed. However, recent observations indicate a particular importance of mold/mycotoxin exposure in individuals with pre-existing dysregulation of the immune system, due to exacerbation of underlying pathophysiology including allergic and non-allergic chronic inflammatory diseases, autoimmune disorders, and even human immunodeficiency virus (HIV) disease progression. In this review, we focus on the impact of mycotoxins regarding their impact on disease progression in pre-existing immune dysregulation. This is complemented by experimental in vivo and in vitro findings to present cellular and molecular modes of action. Furthermore, we discuss hypothetical mechanisms of action, where evidence is missing since much remains to be discovered.

A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects.

Chronic kidney disease (CKD) is generally progressive and irreversible, structural or functional renal impairment for 3 or more months affecting multiple metabolic pathways. Recently, the composition, dynamics, and stability of a patient's microbiota has been noted to play a significant role during disease onset or progression. Increasing urea concentration during CKD can lead to an acceleration of the process of kidney injury leading to alterations in the intestinal microbiota that can increase the production of gut-derived toxins and alter the intestinal epithelial barrier. A detailed analysis of the relationship between the role of intestinal microbiota and the development of inflammation within the symbiotic and dysbiotic intestinal microbiota showed significant changes in kidney dysfunction. Several recent studies have determined that dietary factors can significantly influence the activation of immune cells and their mediators. Moreover, dietary changes can profoundly affect the balance of gut microbiota. The aim of this review is to present the importance and factors influencing the differentiation of the human microbiota in the progression of kidney diseases, such as CKD, IgA nephropathy, idiopatic nephropathy, and diabetic kidney disease, with particular emphasis on the role of the immune system. Moreover, the effects of nutrients, bioactive compounds on the immune system in development of chronic kidney disease were reviewed.

Diet-Regulating Microbiota and Host Immune System in Liver Disease.

The gut microbiota has been known to modulate the immune responses in chronic liver diseases. Recent evidence suggests that effects of dietary foods on health care and human diseases are related to both the immune reaction and the microbiome. The gut-microbiome and intestinal immune system play a central role in the control of bacterial translocation-induced liver disease. Dysbiosis, small intestinal bacterial overgrowth, translocation, endotoxemia, and the direct effects of metabolites are the main events in the gut-liver axis, and immune responses act on every pathways of chronic liver disease. Microbiome-derived metabolites or bacteria themselves regulate immune cell functions such as recognition or activation of receptors, the control of gene expression by epigenetic change, activation of immune cells, and the integration of cellular metabolism. Here, we reviewed recent reports about the immunologic role of gut microbiotas in liver disease, highlighting the role of diet in chronic liver disease.

Bifidobacteria-mediated immune system imprinting early in life.

Immune-microbe interactions early in life influence the risk of allergies, asthma, and other inflammatory diseases. Breastfeeding guides healthier immune-microbe relationships by providing nutrients to specialized microbes that in turn benefit the host's immune system. Such bacteria have co-evolved with humans but are now increasingly rare in modern societies. Here we show that a lack of bifidobacteria, and in particular depletion of genes required for human milk oligosaccharide (HMO) utilization from the metagenome, is associated with systemic inflammation and immune dysregulation early in life. In breastfed infants given Bifidobacterium infantis EVC001, which expresses all HMO-utilization genes, intestinal T helper 2 (Th2) and Th17 cytokines were silenced and interferon ß (IFNß) was induced. Fecal water from EVC001-supplemented infants contains abundant indolelactate and B. infantis-derived indole-3-lactic acid (ILA) upregulated immunoregulatory galectin-1 in Th2 and Th17 cells during polarization, providing a functional link between beneficial microbes and immunoregulation during the first months of life.

The Role of Trogocytosis in the Modulation of Immune Cell Functions.

Trogocytosis is an active process, in which one cell extracts the cell fragment from another cell, leading to the transfer of cell surface molecules, together with membrane fragments. Recent reports have revealed that trogocytosis can modulate various biological responses, including adaptive and innate immune responses and homeostatic responses. Trogocytosis is evolutionally conserved from protozoan parasites to eukaryotic cells. In some cases, trogocytosis results in cell death, which is utilized as a mechanism for antibody-dependent cytotoxicity (ADCC). In other cases, trogocytosis-mediated intercellular protein transfer leads to both the acquisition of novel functions in recipient cells and the loss of cellular functions in donor cells. Trogocytosis in immune cells is typically mediated by receptor-ligand interactions, including TCR-MHC interactions and Fcγ receptor-antibody-bound molecule interactions. Additionally, trogocytosis mediates the transfer of MHC molecules to various immune and non-immune cells, which confers antigen-presenting activity on non-professional antigen-presenting cells. In this review, we summarize the recent advances in our understanding of the role of trogocytosis in immune modulation.

Differential Health Effects on Inflammatory, Immunological and Stress Parameters in Professional Soccer Players and Sedentary Individuals after Consuming a Synbiotic. A Triple-Blinded, Randomized, Placebo-Controlled Pilot Study.

The main objective of this research was to carry out an experimental study, triple-blind, on the possible immunophysiological effects of a nutritional supplement (synbiotic, Gasteel Plus®, Heel España S.A.U.), containing a mixture of probiotic strains, such as Bifidobacterium lactis CBP-001010, Lactobacillus rhamnosus CNCM I-4036, and Bifidobacterium longum ES1, as well as the prebiotic fructooligosaccharides, on both professional athletes and sedentary people. The effects on some inflammatory/immune (IL-1ß, IL-10, and immunoglobulin A) and stress (epinephrine, norepinephrine, dopamine, serotonin, corticotropin-releasing hormone (CRH), Adrenocorticotropic hormone (ACTH), and cortisol) biomarkers were evaluated, determined by flow cytometer and ELISA. The effects on metabolic profile and physical activity, as well as on various parameters that could affect physical and mental health, were also evaluated via the use of accelerometry and validated questionnaires. The participants were professional soccer players in the Second Division B of the Spanish League and sedentary students of the same sex and age range. Both study groups were randomly divided into two groups: a control group-administered with placebo, and an experimental group-administered with the synbiotic. Each participant was evaluated at baseline, as well as after the intervention, which lasted one month. Only in the athlete group did the synbiotic intervention clearly improve objective physical activity and sleep quality, as well as perceived general health, stress, and anxiety levels. Furthermore, the synbiotic induced an immunophysiological bioregulatory effect, depending on the basal situation of each experimental group, particularly in the systemic levels of IL-1ß (increased significantly only in the sedentary group), CRH (decreased significantly only in the sedentary group), and dopamine (increased significantly only in the athlete group). There were no significant differences between groups in the levels of immunoglobulin A or in the metabolic profile as a result of the intervention. It is concluded that synbiotic nutritional supplements can improve anxiety, stress, and sleep quality, particularly in sportspeople, which appears to be linked to an improved immuno-neuroendocrine response in which IL-1ß, CRH, and dopamine are clearly involved.

Impact of Early Life Nutrition on Children's Immune System and Noncommunicable Diseases Through Its Effects on the Bacterial Microbiome, Virome and Mycobiome.

The first 1000 days of life, including the intrauterine period, are regarded as a fundamental stepping stone for the development of a human. Unequivocally, nutrition during this period plays a key role on the proper development of a child, both directly through the intake of essential nutrients and indirectly by affecting the composition of the gut microbiota. The gut microbiota, including bacteria, viruses, fungi, protists and other microorganisms, is a highly modifiable and adaptive system that is influenced by diet, lifestyle, medicinal products and the environment. Reversely, it affects the immune system in multiple complex ways. Many noncommunicable diseases (NCDs) associated with dysbiosis are "programmed" during childhood. Nutrition is a potent determinant of the children's microbiota composition and maturation and, therefore, a strong determinant of the NCDs' programming. In this review we explore the interplay between nutrition during the first 1000 days of life, the gut microbiota, virome and mycobiome composition and the development of NCDs.

The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies.

Infectious diseases and infections remain a leading cause of death in low-income countries and a major risk to vulnerable groups, such as infants and the elderly. The immune system plays a crucial role in the susceptibility, persistence, and clearance of these infections. With 70-80% of immune cells being present in the gut, there is an intricate interplay between the intestinal microbiota, the intestinal epithelial layer, and the local mucosal immune system. In addition to the local mucosal immune responses in the gut, it is increasingly recognized that the gut microbiome also affects systemic immunity. Clinicians are more and more using the increased knowledge about these complex interactions between the immune system, the gut microbiome, and human pathogens. The now well-recognized impact of nutrition on the composition of the gut microbiota and the immune system elucidates the role nutrition can play in improving health. This review describes the mechanisms involved in maintaining the intricate balance between the microbiota, gut health, the local immune response, and systemic immunity, linking this to infectious diseases throughout life, and highlights the impact of nutrition in infectious disease prevention and treatment.