An emerging maestro of immune regulation: how DOT1L orchestrates the harmonies of the immune system.

The immune system comprises a complex yet tightly regulated network of cells and molecules that play a critical role in protecting the body from infection and disease. The activity and development of each immune cell is regulated in a myriad of ways including through the cytokine milieu, the availability of key receptors, via tailored intracellular signalling cascades, dedicated transcription factors and even by directly modulating gene accessibility and expression; the latter is more commonly known as epigenetic regulation. In recent years, epigenetic regulators have begun to emerge as key players involved in modulating the immune system. Among these, the lysine methyltransferase DOT1L has gained significant attention for its involvement in orchestrating immune cell formation and function. In this review we provide an overview of the role of DOT1L across the immune system and the implications of this role on health and disease. We begin by elucidating the general mechanisms of DOT1L-mediated histone methylation and its impact on gene expression within immune cells. Subsequently, we provide a detailed and comprehensive overview of recent studies that identify DOT1L as a crucial regulator of immune cell development, differentiation, and activation. Next, we discuss the potential mechanisms of DOT1L-mediated regulation of immune cell function and shed light on how DOT1L might be contributing to immune cell homeostasis and dysfunction. We then provide food for thought by highlighting some of the current obstacles and technical limitations precluding a more in-depth elucidation of DOT1L's role. Finally, we explore the potential therapeutic implications of targeting DOT1L in the context of immune-related diseases and discuss ongoing research efforts to this end. Overall, this review consolidates the current paradigm regarding DOT1L's role across the immune network and emphasises its critical role in governing the healthy immune system and its potential as a novel therapeutic target for immune-related diseases. A deeper understanding of DOT1L's immunomodulatory functions could pave the way for innovative therapeutic approaches which fine-tune the immune response to enhance or restore human health.

Spatial heterogeneity and functional zonation of living tissues and organs in situ.

In most organs, resources such as nutrients, oxygen, and physiologically active substances are unevenly supplied within the tissue spaces. Consequently, different tissue functions are exhibited in each space. This spatial heterogeneity of tissue environments arises depending on the spatial arrangement of nutrient vessels and functional vessels, leading to continuous changes in the metabolic states and functions of various cell types from regions proximal to these vessels to distant regions. This phenomenon is referred to as "zonation". Traditional analytical methods have made it difficult to investigate this zonation in detail. However, recent advancements in intravital imaging, spatial transcriptomics, and single-cell transcriptomics technologies have facilitated the discovery of "zones" in various organs and elucidated their physiological roles. Here, we outline the spatial differences in the immune system within each zone of organs. This information provides a deeper understanding of organs' immune systems.

[Immunological foundations of neurological diseases]. / Immunologische Grundlagen neurologischer Erkrankungen.

BACKGROUND: Neurodegenerative diseases represent an increasing challenge in ageing societies, as only limited treatment options are currently available. OBJECTIVE: New research methods and interdisciplinary interaction of different disciplines have changed the way neurological disorders are viewed and paved the way for the comparatively new field of neuroimmunology, which was established in the early 1980s. Starting from neurological autoimmune diseases, such as multiple sclerosis, knowledge about the involvement of immunological processes in other contexts, such as stroke or traumatic brain injury, has been significantly expanded in recent years. MATERIAL AND METHODS: This review article provides an overview of the role of the immune system and the resulting potential for novel treatment approaches. RESULTS: The immune system plays a central role in fighting infections but is also able to react to the body's own signals under sterile conditions and cause inflammation and subsequent adaptive immune responses through the release of immune mediators and the recruitment and differentiation of certain immune cell types. This can be beneficial in initiating healing processes; however, chronic inflammatory conditions usually have destructive consequences for the tissue and the organism and must be interrupted. CONCLUSION: It is now known that different cells of the immune system play an important role in neurological diseases. Regulatory mechanisms, which are mediated by regulatory T cells or Th2 cells, are usually associated with a good prognosis, whereas inflammatory processes and polarization towards Th1 or Th17 have a destructive character. Novel immunomodulators, which are also increasingly being used in cancer treatment, can now be used in a tissue-specific manner and therefore offer great potential for use in neurological diseases.

Cytokine expression profiles in children and adolescents with tic disorders.

The etiology of tic disorders (TDs) is not precisely known, although several lines of evidence suggest involvement of the immune system in pathogenesis. Here, we aimed to determine the expression levels of pro-inflammatory and anti-inflammatory cytokines in children with TD and compare them with those of healthy controls. Furthermore, we also evaluated their association with clinical variables in the TD group. Within the study period, 88 children with tic disorders and 111 healthy control children were enrolled. Most children with tic disorders were diagnosed with Tourette's disorder (n = 47, 53.4%) or persistent motor tic disorder (n = 39, 44.3%), while the remainder (n = 2, 2.3%) were diagnosed with persistent vocal tic disorder. We found that children with tic disorders had significantly elevated levels of IL-1ß, TNF-α, IL-6 and IL-4 expression, while we detected lower expression levels of IL-17 in children with tic disorders. Our findings provide a molecular landscape of cytokine expression in children with TD, which may suggest a proinflammatory state not affected by the presence of comorbidity and symptom severity. Delineating the contribution of alterations in the immune system to the pathogenesis of tic disorders may pave the way for better therapeutic interventions.

Italian validation of the body odor disgust scale.

Introduction: Disgust sensitivity to body odors plays a role in a set of psychological mechanisms supposedly evolved to avoid pathogens. To assess individual differences in body odor disgust, we previously developed the body odor disgust scale (BODS) and validated it in English. The BODS presents six scenarios where disgust could be evoked by smells coming from an internal source and an external source. The present study aimed to validate the BODS in the Italian population and to find further evidence for its structural, construct, and criterion validity. Methods: We used two large samples (N = 1,050, F = 527; and N = 402, F = 203, respectively) that were representative of the Italian population for sex and age. Results: Across these two studies, we confirmed the hypothesized bifactor structure, with all the items loading onto a general body odor disgust sensitivity factor, and on two specific factors related to the internal structure. In terms of construct validity, we found that the BODS converged with pathogen disgust sensitivity of the three-domain disgust scale (TDDS) but was distinct from a general propensity to experience negative emotions. The BODS showed criterion validity in predicting the behavioral intentions toward COVID-19 avoidance behavior, although it did not seem to be incrementally valid when compared to the TDDS pathogen subscale. We also established scalar measurement invariance of the BODS regarding gender and found that women display higher levels of BODS. Discussion: Results from the Italian version of the BODS indicate its structural, construct, nomological and criterion validity. Furthermore, our result on sex differences in disgust sensitivity are consistent with previous literature, and we discuss them in the broader context of cross-cultural and primate findings that points toward a possible evolutionary explanation of this difference.

Antimicrobial peptides (AMPs) from microalgae as an alternative to conventional antibiotics in aquaculture.

The excessive use of conventional antibiotics has resulted in significant aquatic pollution and a concerning surge in drug-resistant bacteria. Efforts have been consolidated to explore and develop environmentally friendly antimicrobial alternatives to mitigate the imminent threat posed by multi-resistant pathogens. Antimicrobial peptides (AMPs) have gained prominence due to their low propensity to induce bacterial resistance, attributed to their multiple mechanisms of action and synergistic effects. Microalgae, particularly cyanobacteria, have emerged as promising alternatives with antibiotic potential to address these challenges. The aim of this review is to present some AMPs extracted from microalgae, emphasizing their activity against common pathogens and elucidating their mechanisms of action, as well as their potential application in the aquaculture industry. Likewise, the biosynthesis, advantages and disadvantages of the use of AMPs are described. Currently, biotechnology tolls are used to enhance the action of these peptides, such as genetically modified microalgae and recombinant proteins. Cyanobacteria are also mentioned as major producers of peptides, among them, the genus Lyngbya is described as the most important producer of bioactive peptides with potential therapeutic use. The majority of cyanobacterial AMPs are of the cyclic type, meaning that they have cysteine and disulfide bridges, thanks to this, their greater antimicrobial activity and selectivity. Likewise, we found that large hydrophobic aromatic amino acid residues increase specificity, and improve antibacterial efficacy. However, based on the results of this review, it is possible to highlight that while microalgae show potential as a source of AMPs, further research in this field is necessary to achieve safe and competitive production. Therefore, the data presented here can aid in the selection of microalgal species, peptide structures, and target bacteria, with the goal of establishing biotechnological platforms for aquaculture applications.

Second bone marrow transplantation into regenerating hematopoiesis enhances reconstitution of immune system.

In bone marrow transplantation (BMT), hematopoiesis-reconstituting cells are introduced following myeloablative treatment, which eradicates existing hematopoietic cells and disrupts stroma within the hematopoietic tissue. Both hematopoietic cells and stroma then undergo regeneration. Our study compares the outcomes of a second BMT administered to mice shortly after myeloablative treatment and the first BMT, with those of a second BMT administered to mice experiencing robust hematopoietic regeneration after the initial transplant. We evaluated the efficacy of the second BMT in terms of engraftment efficiency, types of generated blood cells, and longevity of function. Our findings show that regenerating hematopoiesis readily accommodates newly transplanted stem cells, including those endowed with a robust capacity for generating B and T cells. Importantly, our investigation uncovered a window for preferential engraftment of transplanted stem cells coinciding with the resumption of blood cell production. Repeated BMT could intensify hematopoiesis reconstitution and enable therapeutic administration of genetically modified autologous stem cells.

Leveraging genetics to investigate causal effects of immune cell phenotypes in periodontitis: a mendelian randomization study.

Introduction: Immune cells are dynamic in the inflammatory environment and play a key role in eradicating periodontal pathogens, modulating immune responses, and instigating tissue destruction. Identifying specific immune cell phenotypes associated with periodontitis risk is essential for targeted immunotherapeutic interventions. However, the role of certain specific immune cell phenotypes in the development of periodontitis is unknown. Mendelian randomization offers a novel approach to reveal causality and address potential confounding factors through genetic instruments. Methods: This two-sample Mendelian randomization study assessed the causal relationship between 731 immune cell phenotypes and periodontitis using the inverse variance weighting method with the GWAS catalog genetic database. Methodological robustness was ensured through Cochran's Q test, MR-Egger regression, MR-PRESSO, and Leave-One-Out analysis. Results: 14 immune cell phenotypes showed potential positive causal associations with periodontitis risk (p < 0.05), suggesting an increased risk, while 11 immune cell phenotypes exhibited potential negative causal associations (p < 0.05), indicating a reduced risk. No significant heterogeneity or pleiotropy was observed. Conclusion: This study underscores certain immune cell types as potential periodontitis risk biomarkers, laying a theoretical foundation for future individualized treatment and precision medicine development.

The role of microglia in early neurodevelopment and the effects of maternal immune activation.

Activation of the maternal immune system during gestation has been associated with an increased risk for neurodevelopmental disorders in the offspring, particularly schizophrenia and autism spectrum disorder. Microglia, the tissue-resident macrophages of the central nervous system, are implicated as potential mediators of this increased risk. Early in development, microglia start populating the embryonic central nervous system and in addition to their traditional role as immune responders under homeostatic conditions, microglia are also intricately involved in various early neurodevelopmental processes. The timing of immune activation may interfere with microglia functioning during early neurodevelopment, potentially leading to long-term consequences in postnatal life. In this review we will discuss the involvement of microglia in brain development during the prenatal and early postnatal stages of life, while also examining the effects of maternal immune activation on microglia and neurodevelopmental processes. Additionally, we discuss recent single cell RNA-sequencing studies focusing on microglia during prenatal development, and hypothesize how early life microglial priming, potentially through epigenetic reprogramming, may be related to neurodevelopmental disorders.

Increasing plasma calprotectin (S100A8/A9) is associated with 12-month mortality and unfavourable functional outcome in critically ill COVID-19 patients.

BACKGROUND: Calprotectin (S100A8/A9) is a pro-inflammatory mediator primarily released from neutrophils. Previous studies have revealed associations between plasma calprotectin, disease severity and in-hospital mortality in unselected COVID-19 patients. OBJECTIVE: We aimed to assess whether plasma calprotectin dynamics during the first week of intensive care are associated with mortality and functional outcome in critically ill COVID-19 patients. METHODS: This prospective study included 498 COVID-19 patients admitted to six intensive care units (ICUs) in Sweden between May 2020 and May 2021. Blood samples were collected on ICU admission and on day 7. The primary outcome was 12-month mortality. Secondary outcomes were functional outcome of survivors at 3 and 12 months, and the need for invasive mechanical ventilation (IMV) or continuous renal replacement therapy (CRRT) during the ICU stay. Functional outcome was assessed by the Glasgow Outcome Scale Extended (GOSE, range 1-8, with < 5 representing an unfavourable outcome). Associations between plasma calprotectin and outcomes were examined in binary logistic regression analyses adjusted for age, sex, BMI, hypertension, smoking, and creatinine. RESULTS: High plasma calprotectin on admission and day 7 was independently associated with increased 12-month mortality. Increasing calprotectin from admission to day 7 was independently associated with higher mortality at 12 months [OR 2.10 (95% CI 1.18-3.74), p = 0.012], unfavourable functional outcome at 3 months [OR 2.53 (95% CI 1.07-6.10), p = 0.036], and the use of IMV [OR 2.23 (95% CI 1.10-4.53), p = 0.027)] and CRRT [OR 2.07 (95% CI 1.07-4.00), p = 0.031)]. A receiver operator characteristic (ROC) model including day 7 calprotectin and age was a good predictor of 12-month mortality [AUC 0.79 (95% CI 0.74-0.84), p < 0.001]. Day 7 calprotectin alone predicted an unfavourable functional outcome at 3 months [AUC 0.67 (95% CI 0.58-0.76), p < 0.001]. CONCLUSION: In critically ill COVID-19 patients, increasing calprotectin levels after admission to the ICU are associated with 12-month mortality and unfavourable functional outcome in survivors. Monitoring plasma calprotectin dynamics in the ICU may be considered to evaluate prognosis in critical COVID-19. STUDY REGISTRATION: ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

A longitudinal evaluation of oxidative stress - mitochondrial dysfunction - ferroptosis genes in anthracycline-induced cardiotoxicity.

BACKGROUND: Antineoplastic medications, including doxorubicin, idarubicin, and epirubicin, have been found to adversely affect the heart due to oxidative stress - mitochondrial dysfunction - ferroptosis (ORMFs), which act as contributing attributes to anthracycline-induced cardiotoxicity. To better understand this phenomenon, the time-resolved measurements of ORMFS genes were analyzed in this study. METHODS: The effect of three anthracycline drugs on ORMFs genes was studied using a human 3D cardiac microtissue cell model. Transcriptome data was collected over 14 days at two doses (therapeutic and toxic). WGCNA identified key module-related genes, and functional enrichment analysis investigated the biological processes quantified by ssGSEA, such as immune cell infiltration and angiogenesis. Biopsies were collected from heart failure patients and control subjects. GSE59672 and GSE2965 were collected for validation. Molecular docking was used to identify anthracyclines's interaction with key genes. RESULTS: The ORMFs genes were screened in vivo or in vitro. Using WGCNA, six co-expressed gene modules were grouped, with MEblue emerging as the most significant module. Eight key genes intersecting the blue module with the dynamic response genes were obtained: CD36, CDH5, CHI3L1, HBA2, HSD11B1, OGN, RPL8, and VWF. Compared with control samples, all key genes except RPL8 were down-regulated in vitro ANT treatment settings, and their expression levels varied over time. According to functional analyses, the key module-related genes were engaged in angiogenesis and the immune system pathways. In all ANT-treated settings, ssGSEA demonstrated a significant down-regulation of angiogenesis score and immune cell activity, including Activated CD4 T cell, Immature B cell, Memory B cell, Natural killer cell, Type 1 T helper cell, and Type 2 T helper cell. Molecular docking revealed that RPL8 and CHI3L1 show significant binding affinity for anthracyclines. CONCLUSION: This study focuses on the dynamic characteristics of ORMFs genes in both human cardiac microtissues and cardiac biopsies from ANT-treated patients. It has been highlighted that ORMFs genes may contribute to immune infiltration and angiogenesis in cases of anthracycline-induced cardiotoxicity. A thorough understanding of these genes could potentially lead to improved diagnosis and treatment of the disease.

Reconstitution of human microglia and resident T cells in the brain of humanized DRAGA mice.

Humanized mouse models are valuable tools for investigating the human immune system in response to infection and injury. We have previously described the human immune system (HIS)-DRAGA mice (HLA-A2.HLA-DR4.Rag1KO.IL-2RgKO.NOD) generated by infusion of Human Leukocyte Antigen (HLA)-matched, human hematopoietic stem cells from umbilical cord blood. By reconstituting human cells, the HIS-DRAGA mouse model has been utilized as a "surrogate in vivo human model" for infectious diseases such as Human Immunodeficiency Virus (HIV), Influenza, Coronavirus Disease 2019 (COVID-19), scrub typhus, and malaria. This humanized mouse model bypasses ethical concerns about the use of fetal tissues for the humanization of laboratory animals. Here in, we demonstrate the presence of human microglia and T cells in the brain of HIS-DRAGA mice. Microglia are brain-resident macrophages that play pivotal roles against pathogens and cerebral damage, whereas the brain-resident T cells provide surveillance and defense against infections. Our findings suggest that the HIS-DRAGA mouse model offers unique advantages for studying the functions of human microglia and T cells in the brain during infections, degenerative disorders, tumors, and trauma, as well as for testing therapeutics in these pathological conditions.

Compromiso inmunológico en pacientes con síndrome de Down. Serie de casos / Immune compromise in patients with Down syndrome. A case series

El síndrome de Down, o trisomía 21, tiene una mortalidad mayor que la población general, debido principalmente a infecciones respiratorias. El objetivo de este trabajo es describir el compromiso inmunológico en una serie de casos de pacientes con síndrome de Down derivados a Inmunología por infecciones recurrentes o por hallazgo patológico de laboratorio, entre el 1 de junio de 2016 y el 31 de mayo de 2022. Se describe el compromiso de la inmunidad en 24 pacientes. Doce pacientes presentaron falla de respuesta a polisacáridos y recibieron quimioprofilaxis antibiótica y/o gammaglobulina sustitutiva. En 3 pacientes, se observó agammaglobulinemia con linfocitos B presentes y se indicó gammaglobulina sustitutiva. En 9 pacientes, se observó linfopenia T y en 1 paciente, compromiso inmune combinado.

Down syndrome, or trisomy 21, has a higher mortality than the general population, mainly due to respiratory tract infections. The objective of this study was to describe immune compromise in a series of cases of patients with Down syndrome referred to the Pediatric Immunology Section due to recurrent infections or pathological laboratory findings between 6/1/2016 and 5/31/2022. Here we describe immune compromise in 24 patients. Twelve patients failed to develop a polysaccharide response and received antibiotic chemoprophylaxis, or gamma globulin replacement therapy. Three patientsdeveloped agammaglobulinemia with presence of B cells and gamma globulin replacement therapy was indicated. Nine patients had T-cell lymphopenia and 1 patient, combined immune compromise.

The place of beta-adrenergic receptor blockers in the treatment of arterial hypertension: from bench-to-bedside.

Arterial hypertension is a multifaceted condition influenced by numerous pathophysiological factors. The key contributors to its pathogenesis encompass an unhealthy lifestyle, dysregulation of the sympathetic nervous system, alterations in the activity of adrenergic receptors, disruptions in sodium metabolism, structural and functional abnormalities in the vascular bed, as well as endothelial dysfunction, low-grade inflammation, oxidative stress etc. Despite extensive research into the mechanisms of arterial hypertension development over the centuries, its pathogenesis remains incompletely understood, and the selection of an effective treatment strategy continues to pose a significant challenge. Arterial hypertension is characterized by a diminished sensitivity of the ß-adrenergic system, leading to the utilization of ß-adrenergic blockers and other antihypertensive drugs in its treatment. This review delves into the mechanisms of action of beta-adrenergic receptor blockers in the treatment of hypertension and their respective effects.

Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis.

Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same dose, have opposite effects on adipogenesis in white adipose tissue (WAT). To investigate the mechanisms involved in these contrasting effects by means of transcriptomic analysis, three groups of male adolescent rats (n = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Both treated groups received a twofold increase in Se dose compared to the control group through water intake for three weeks. Following treatment, WAT was removed and frozen at -80 °C until subsequent use for RNA extraction, endogenous antioxidant enzymatic activities determination, and quantification of H2O2 and malondialdehyde. NS rats displayed a larger number of differentially expressed genes and cellular processes impacted than S rats. Remarkably, these changes involved upregulation of gene expression associated with the immune system, catabolism, mitochondrial function, and oxidative balance. NS rats presented an increase in antioxidant enzymes activity, alongside an accumulation of H2O2 and malondialdehyde levels. The expression level of 81 genes related to oxidative stress was significantly affected in NS rats. Analyzing the KEGG pathway enrichment revealed that NS rats exhibited increased activity in key catabolic pathways and decreased activity in crucial growth signaling processes. These changes contribute to the mass decrease in WAT found in NS rats. These results suggest a possible application of SeNPs in WAT reduction and induction of the immune response during adolescence.

Transcriptional Evaluation of Neuropeptides, Hormones, and Tissue Repair Modulators in the Skin of Gilthead Sea Bream (Sparus aurata L.) Subjected to Mechanical Damage.

The skin of bony fish is the first physical barrier and is responsible for maintaining the integrity of the fish. Lesions make the skin vulnerable to potential infection by pathogens present in the aquatic environment. In this way, wound repair has barely been studied in gilthead sea bream. Thus, this study investigated the modulation of peripheral neuro-endocrine and tissue repair markers at the transcriptional level in the skin of teleost fish subjected to mechanical damage above or below the lateral line (dorsal and ventral lesions, respectively). Samples were evaluated using RT-qPCR at 2-, 4-, and 20-days post-injury. Fish with a ventral lesion presented a trend of progressive increase in the expressions of corticotropin-releasing hormone (crh), pro-opiomelanocortin-A (pomca), proenkephalin-B (penkb), cholecystokinin (cck), oxytocin (oxt), angiotensinogen (agt), and (less pronounced) somatostatin-1B (sst1b). By contrast, fish with a dorsal lesion registered no significant increase or biological trend for the genes evaluated at the different sampling times. Collectively, the results show a rapid and more robust response of neuro-endocrine and tissue repair markers in the injuries below than above the lateral line, which could be attributable to their proximity to vital organs.

Mechanisms of Male Reproductive Sterility Triggered by Dysbiosis of Intestinal Microorganisms.

The intestinal microbiota, comprised of bacteria, archaea, and phages, inhabits the gastrointestinal tract of the organism. Male reproductive sterility is currently a prominent topic in medical research. Increasing research suggests that gut microbiota dysbiosis can result in various reproductive health problems. This article specifically investigates the impact of gut microbiota dysbiosis on male reproductive infertility development. Gut microbiota imbalances can disrupt the immune system and immune cell metabolism, affecting testicular growth and sperm production. This dysfunction can compromise the levels of hormones produced and secreted by the endocrine glands, affecting male reproductive health. Furthermore, imbalance of the gut microbiota can disrupt the gut-brain-reproductive axis, resulting in male reproductive infertility. This article explores how the imbalance of the gut microbiota impacts male reproductive infertility through immune regulation, endocrine regulation, and interactions of the gut-brain-reproductive axis, concluding with recommendations for prevention and treatment.

The Impact of Vitamin D on Immune Function and Its Role in Hashimoto's Thyroiditis: A Narrative Review.

Vitamin D, an essential nutrient, plays a crucial role in numerous biological functions, acting as a hormone and being important for the proper functioning of the immune system. This review illustrates the interactions between adequate vitamin D levels and an appropriate immune response, highlighting the implications for Hashimoto's thyroiditis (HT), a chronic inflammation of the thyroid characterized by the production of autoantibodies. A comprehensive review of the existing literature shows that vitamin D inhibits the secretion of pro-inflammatory cytokines, leading to an improvement in the clinical picture in HT by switching from a pro-inflammatory to immune balance. Vitamin D supplementation has been shown to reduce elevated serum levels of thyroid peroxidase antibodies, a key marker of HT. Although the results are conflicting, the evidence suggests that an adequate vitamin D intake supports the immune function and counteracts autoimmune conditions such as HT by improving their symptoms. There is evidence of vitamin D's key role in supporting the immune system function and managing autoimmunity, such as in HT. An adequate vitamin D intake is crucial for improving the clinical picture and the symptoms of HT.

Biological Significance of Probiotic Microorganisms from Kefir and Kombucha: A Review.

(1) Background: The human microbiota is essential for maintaining a healthy body. The gut microbiota plays a protective role against pathogenic bacteria. Probiotics are live microorganisms capable of preventing and controlling gastrointestinal and balancing the immune system. They also aid in better nutrients and vitamins absorption. Examples of natural probiotic cultures are kefir and kombucha. (2) Methods: Therefore, the aim of this review was to address the beneficial properties of probiotic kefir and kombucha using a Boxplot analysis to search for scientific data in the online literature up to January 2024: (Latin American and Caribbean Health Sciences (LILACS), PubMed, Medical Literature Analysis (MED-LINE), Science Direct, Google Scholar/Google Academic, Bioline Inter-national and Springer Link). Boxplots showed the summary of a set of data "Index Terms-Keywords" on kefir and kombucha in three languages (English, Portuguese and Spanish). (3) Results: Google Scholar was the database with the highest number of articles found, when the search for the keywords used in the study (containing ~4 × 106-~4 million articles available). This was Followed by the Science Direct database, containing ~3 × 106-~3 million articles available, and the BVS databases-Biblioteca Virtual de Saúde (Virtual Health Library) e Lilacs, both containing a value of ~2 × 106-~2 million articles available. The databases containing the smallest number of articles found were Nutrients and Medline, both containing a value of ≤0.1 × 106-≤100 thousand articles. (4) Conclusions: Scientific studies indicate that kefir and kombucha certainly contain various functional properties, such as antimicrobial, antitumor, anticarcinogenic and immunomodulatory activity, in addition to having a microbiological composition of probiotic bacteria and yeasts. Kefir and kombucha represent key opportunities in the food and clinic/medical fields.