Normal Human Microbiota Research Articles

The effect of the probiotic bacteria <i>Akkermansia Muciniphila</i> in intestinal homeostasis and dss-induced inflammation in mice

Akkermansia muciniphila is a Gram-negative anaerobic bacterium, a component of the normal human intestinal microbiota. A decrease in the presence of this bacterium is associated with pathologies, including metabolic disorders, intestinal inflammation and colorectal cancer. A. muciniphila is a probiotic approved for patients with diabetes and obesity. In recent years, A. muciniphila was studied in the control of intestinal inflammation and colorectal cancer. The exact mechanisms of A. muciniphila action remain unclear, while the use of different administration protocols shows different effects in mouse models of colitis and colorectal cancer. We reported that A. muciniphila has distinct effects on intestinal mucin production depending on viable or pasteurized form of bacteria. Another factor affecting the outcome of the A. muciniphila administration is the number of bacteria. To address how the dose of bacteria may affect the severity of acute intestinal inflammation wild-type mice were subjected to daily oral injections with 10⁸ CFU or 109 CFU of viable A. muciniphila for two weeks; the control group was injected with PBS. After that, groups were subjected to the induction of acute colitis by adding 7% DSS to drinking water for five days. 8 days after the onset of colitis induction, a morphometric assessment of the colitis severity was performed. Mice given a high dose of A. muciniphila (109 CFU) were found to be protected from developing severe colitis. RT-PCR analysis of colon samples from mice receiving a high dose of bacteria showed an increase in the gene expression of antimicrobial peptides, IL-17A, IL-17F. Interestingly, the protective effect of A. muciniphila was observed only in a high dose group, but not in a low dose group. Our data suggest that A. muciniphila provides the protective effect in colitis and highlight the importance of selecting the dose of the bacterium for proper interpretation.

Efficacy of Facial Mask Use in COVID-19 Transmission Using a Bacterial Model

Abstract The prevention of COVID-19, caused by SARS-CoV-2, involves reducing transmission of infectious respiratory droplets and aerosols with different methods, including the use of face masks. There have been a variety of studies published about the effectiveness of face masks — they have been recognised as an inexpensive yet expedient prevention method. In this research we aimed to investigate the microbial contamination of used face masks and to compare the results based on mask usage time to determine the efficiency of facial mask use against COVID-19. Microbiological contamination of 51 used face masks was analysed by the imprinting method on suitable cultivation agars and colony forming units were determined. The majority of microorganisms found in our study were those of normal human skin and respiratory tract microbiota. A greater number of bacterial species was found on the outsides of the facial masks, which furthermore increased with prolonged usage time. We conclude that face mask use is effective in both detaining excreted microorganisms as well as protecting the wearer from microbes in the air, and therefore, should be implemented in the prevention strategies of respiratory diseases. Furthermore, our results show the importance of correct facial mask usage by their contamination with a spectrum of microorganisms.

Normalna ljudska mikrobiota i disbioza - implikacije po zdravlje i bolest

The normal human microbiota, formerly called the "microbial flora," consists of bacteria, fungi, viruses, and parasites that colonise the skin and mucous membranes of the respiratory, gastrointestinal, and genitourinary tracts. The number and diversity of microorganisms varies between different body niches and is greatest in the intestinal tract. The microbiota contributes to the homeostasis of the human organism by preventing colonisation by pathogenic microorganisms, participating in digestive processes and metabolism, and regulating immune functions. Various environmental and genetic factors can lead to an imbalance in the human microbiota, called dysbiosis, which can affect human health. Dysbiosis is usually the result of decreased microbial diversity and a lower number of saprophytic microorganisms, followed by an overgrowth of opportunistic species. The most common diseases directly related to intestinal dysbiosis are antibiotic-associated diarrhoea and pseudomembranous colitis, both of which are associated with the excessive growth of harmful bacteria and Clostridioides difficile following broad-spectrum antibiotic therapy. Dysbiosis is associated with various health conditions or diseases such as acne, psoriasis, eczema, chronic obstructive pulmonary disease, inflammatory bowel disease, obesity, metabolic syndrome, type 2 diabetes, autoimmune diseases and allergies, neurological diseases such as Parkinson's disease, Alzheimer's disease, epilepsy and stroke, depression, anxiety, infertility, preterm birth, and malignancies.

Phenylthiazoles with potent & optimum selectivity toward Clostridium difficile.

Clostridium difficile (C. difficile) is one of the most threatening bacteria globally, causing high mortality and morbidity in humans and animals, and is considered a public health threat that requires urgent and aggressive action. Interruption of the human gut microbiome and the development of antibiotic resistance urgently require development and synthesis of effective alternative antibiotics with minimal effects on the normal gut microbial flora. In this study, cyclization of the aminoguanidine head to the thiazole nucleus while maintaining its other pharmacophoric features leads to selective targeting of Clostridioides difficile as shown in the graphical abstract. The most promising compound, 5, was significantly more efficient than vancomycin and metronidazole against six strains of C. diff with MIC values as low as 0.030 μg mL-1. Additionally, compound 5 was superior to vancomycin and metronidazole, showing no inhibition toward nine tested strains of the normal human gut microbiota (>64 μg mL-1). The high safety profile of compound 5 was also observed with two cell lines HRT-18 and Vero cells.

Invasive Malassezia Infections.

The Malassezia species are dimorphic fungi that require lipids such as olive oil for their growth. They are constituents of the normal human skin microbiota and can affix to the host or other surfaces through the establishment of biofilms. Malassezia species are accountable for superficial mycoses like folliculitis. Additionally, they are capable of causing invasive infections, such as of the bloodstream, in neonates and immunocompromised patients, albeit infrequently. Catheter-associated bloodstream infections in neonates are the most commonly reported invasive cases. Remarkably, unlike other invasive fungal infections, neutropenia and the use of broad-spectrum antibiotics do not seem to contribute to the risk of invasive Malassezia infections. Nosocomial outbreaks of Malassezia infections have been reported. While most cases of invasive Malassezia infection are fungemia, they seldom give rise to disseminated lesions in various organs. The diagnosis can be confirmed by the visualization of characteristic yeasts through histologic or cytologic examination of a biopsy or needle aspiration specimen, or via positive culture results from sterile sites. The prognosis for invasive Malassezia infection is generally favorable, with few reports of treatment failure. Nevertheless, due to the limited number of cases, evidence-based treatment recommendations are wanting. Management of invasive Malassezia infections linked to central venous catheters includes removal of the catheter, cessation of intravenous lipid emulsion, and intravenous administration of appropriate antifungal agents.

Роль пробиотиков в профилактике и лечении заболеваний

Пробиотики, включающие бактерии и дрожжи, представляют собой живые микроорганизмы, оказывающие благотворное влияние на здоровье человека. Некоторые из этих микроорганизмов составляют часть нормальной микробиоты кишечника человека, где они живут в симбиотических отношениях. В последнее время пробиотические микроорганизмы постоянно изучаются и их применение рассматривается в перспективных методах профилактики и лечения различных заболеваний. Клинические испытания и эксперименты in vitro, in vivo расширили текущее понимание важной роли, которую пробиотики играют при заболеваниях, связанных с микробиомом кишечника человека. Во многих исследованиях отмечается, что пробиотики участвуют в формировании кишечной микробиоты, что приводит к потенциальному контролю течения множества заболеваний кишечника и содействует общему оздоровлению. Убедительные доказательства в пользу использования пробиотиков при лечении таких заболеваний, связанных с микробиомом кишечника (ассоциированная диарея, хронические запоры, синдром раздраженного кишечника, колоректальный рак и различные расстройства функций желудочно-кишечного тракта) как антибиотик. Пробиотики также используются для лечения и профилактики заболеваний, не связанных с желудочно-кишечным трактом, таких как атопический дерматит, аллергия, сердечно-сосудистые заболевания, урогенитальные инфекции и раковые заболевания. Однако в этих случаях точные механизмы воздействия пробиотиков недостаточно изучены и требуют дальнейших исследований в этом направлении. Целью данной статьи является анализ современной литературы о применении пробиотиков в профилактике и лечении различных заболеваний.

Methodology for Integral Study of Antagonistic Activity of Normal Nasal Microbiota to Select Potential Probiotics Efficient in Eradication of Staphylococcus aureus.

The aim of this study was the development of a methodology for the integral study of the antagonistic activity of normal human microbiota against Staphylococcus aureus to enable direct selection (without prior isolation of pure cultures) of potentially highly efficient probiotic preparations. The selection of bacterial representatives of normal human nasal microbiota capable of antagonizing S. aureus was carried out using two complimentary methods: replica-plating and deferred antagonism procedures. The material of the anterior nares from healthy human subjects was plated onto the surface of different nutrient media agar plates followed by incubation under appropriate conditions. The grown bacterial colonies were replica-plated to Petri dishes with nutrient agar overlayed with a thin layer of a soft agar which contained the culture of an indicator S. aureus strain. This agar also supported the growth of potential probiotic strains. The potential probiotic strains were selected by their ability to suppress the growth of S. aureus around their colonies. Most active strains-inhibitors may be used to develop probiotic preparations with targeted activity against S. aureus.

Corynebacterium striatum Prosthetic Joint Infection Successfully Treated with Long-Term Dalbavancin

Arthroplasty surgery is a common procedure that significantly improves quality of life. The most feared complication is prosthetic joint infection (PJI), which occurs more often following revision surgery. Staphylococci are the most prevalent bacteria in PJIs, although many other pathogens have been reported. We describe a case of PJI in a 75-year-old farmer following revision surgery caused by Corynebacterium striatum, an unusual agent which normally occurs in the normal human skin microbiota with perceived low pathogenicity. Following a cemented right-sided total hip arthroplasty in 2006, a one-stage revision due to an osteolytic process in the right femur took place in 2020 with negative intraoperative tissue cultures. Three weeks later, the patient presented a fulminant infection which was treated with debridement, antibiotics, and implant retention (DAIR). Tissue biopsies showed C. striatum in 6/6 samples including small colony variants. Genome sequencing showed that all isolates differed by ≤6 SNPs with the same gene content related to resistance (tet(W) and erm(X)). The patient was sequentially treated with vancomycin, linezolid, and daptomycin, but due to side effects, treatment was changed to 12 weeks of dalbavancin as a 1000 mg loading dose followed by 500 mg intravenously/week. Impaired renal function during vancomycin treatment was normalized, and >1 year after finishing antibiotic treatment the outcome was still favourable. In conclusion, a case of a fulminant early post-interventional PJI due to C. striatum was successfully treated with DAIR and long-term dalbavancin therapy without any adverse reactions.

Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students.

The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.

Biofilm formation, multidrug-resistance and clinical infections of Staphylococcus haemolyticus: A brief review

Coagulase-negative staphylococci (CoNS) have been associated with a range of human health issues such as medical device-related infection, localized skin infection, or direct infection, are recognized as comprising the main part of human normal microbiota and associated with severe and intensive infections, causing infections in humans, especially immunocompromised patients and neonates. S. haemolyticus is, after Staphylococcus epidermidis, the second most frequently isolated CoNS from clinical cases, notably from blood infections, including sepsis. The most important factor might be the ability to acquire multiresistance against available antimicrobial agents, even glycopeptides. It is widespread in hospitals and among medical staff, resulting in being an emerging microbe causing nosocomial infections. This review discuss aspects of S. haemolyticus bloodstream infections associated, virulence factors, and the ability of biofilm formation on medical devices surfaces. The great adaptability and the ability to survive in the hospital environment, especially on medical devices, S. haemolyticus becomes a crucial factor in nosocomial infections caused by multiresistant strains.

Secondary Dysfunction of the Intestinal Barrier in the Pathogenesis of Complications of Acute Poisoning.

The last decade has been marked by an exponential increase in the number of publications on the physiological role of the normal human gut microbiota. The idea of a symbiotic relationship between the human organism and normal microbiota of its gastrointestinal tract has been firmly established as an integral part of the current biomedical paradigm. However, the type of this symbiosis varies from mutualism to parasitism and depends on the functional state of the host organism. Damage caused to the organism by external agents can lead to the emergence of conditionally pathogenic properties in the normal gut microbiota, mediated by humoral factors and affecting the outcome of exogenous exposure. Among the substances produced by symbiotic microbiota, there are an indefinite number of compounds with systemic toxicity. Some occur in the intestinal chyme in potentially lethal amounts in the case they enter the bloodstream quickly. The quick entry of potential toxicants is prevented by the intestinal barrier (IB), a set of structural elements separating the intestinal chyme from the blood. Hypothetically, severe damage to the IB caused by exogenous toxicants can trigger a leakage and subsequent systemic redistribution of toxic substances of bacterial origin. Until recently, the impact of such a redistribution on the outcome of acute exogenous poisoning remained outside the view of toxicology. The present review addresses causal relationships between the secondary dysfunction of the IB and complications of acute poisoning. We characterize acute systemic toxicity of such waste products of the normal gut microflora as ammonia and endotoxins, and demonstrate their involvement in the formation of such complications of acute poisoning as shock, sepsis, cerebral insufficiency and secondary lung injuries. The principles of assessing the functional state of the IB and the approaches to its protection in acute poisoning are briefly considered.

Some mechanisms of Lactobacillus reuteri action as a probiotic microorganism

Some morphological, physiological and biochemical characteristics of the probiotic species of lactic acid bacteria Lactobacillus reuteri are presented in the work. This species, according to literature sources, were isolated from the normal human microbiota, other members of the class Mammalia, as well as broilers and sourdough. The study of literature and Internet sources identified the importance of using different strains of L. reuteri in modern dietary supplements.Some physiological features of this microorganism in terms of positive effects on the functioning of the human gastrointestinal tract and the formation of immunity were considered. According to processed datait is concluded that there is a necessity for further practical study of L. reuteri as a potential probiotic for the pharmaceutical and food industries.

Sweat contamination induced surgical site infections after spine surgery: Three case reports and literature review.

Introduction and importanceSurgical site infection (SSI) is one of the most intractable complications following spine surgery during the early postoperative stage. Elderly (age > 70 years), body mass index > 30, smoking, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, anemia, low serum albumin, operation time > 3 h, and perioperative blood loss > 500 mL are the common risk factors of SSI after spine surgery. However, there are few published reports about sweat contamination induced surgical site infections with Staphylococcus epidermidis up to date. Staphylococcus epidermidis is a permanent member of the normal human microbiota and has emerged as an important opportunistic pathogen in SSI. We aim to detect the influence of sweat infiltration on SSI with Staphylococcus epidermidis and effective management.Case presentationA 73-year-old male, a 54-year-old male and a 73-year-old female were admitted to our hospital. All of them underwent posterior compression and fusion surgery with internal fixation and got surgical site infection after primary surgery. Two of them suffered moderate surgical site infection while the third patient with comorbidities suffered severe surgical site infection. Antibiotic therapy and debridement with internal fixation retained were utilized during which microbiological culture were taken. The moderate infection patients got fully recovered after debridement and primary suture while the serious one had recurrence after the first debridement, and then the second operation was performed. SSI, however, relapsed after three days. Vacuum-assisted closure (VAC) system was placed in the third debridement. The severe patient got well recovered and discharged after displacement of VAC system.Clinical discussionThis report serves to explore a normal but overlooked factor for SSI. SSI is one of the most intractable complications after spine surgery and the report introduce some uncomplicated but effective methods to moderate and severe SSI.ConclusionSweat-contaminated is an inducement of SSI with Staphylococcus epidermidis that should attract surgeons' attention. For mild infection, changing dressing and infrared treatment can achieve good results. For moderate infection, one debridement and primary suture are enough. For severe infection, early application of VAC system can reduce the number of debridement and achieve good clinical outcome.

Evaluation of bisphenylthiazoles as a promising class for combating multidrug-resistant fungal infections.

To minimize the intrinsic toxicity of the antibacterial agent hydrazinyloxadiazole 1, the hydrazine moiety was replaced with ethylenediamine (compound 7). This replacement generated a potent antifungal agent with no antibacterial activity. Notably, use of a 1,2-diaminocyclohexane moiety, as a conformationally-restricted isostere for ethylenediamine, potentiated the antifungal activity in both the cis and trans forms of N-(5-(2-([1,1’-biphenyl]-4-yl)-4-methylthiazol-5-yl)-1,3,4-oxadiazol-2-yl)cyclohexane-1,2-diamine (compounds 16 and 17). Both compounds 16 and 17 were void of any antibacterial activity; nonetheless, they showed equipotent antifungal activity in vitro to that of the most potent approved antifungal agent, amphotericin B. The promising antifungal effects of compounds 16 and 17 were maintained when assessed against an additional panel of 26 yeast and mold clinical isolates, including the Candida auris and C. krusei. Furthermore, compound 17 showed superior activity to amphotericin B in vitro against Candida glabrata and Cryptococcus gattii. Additionally, neither compound inhibited the normal human microbiota, and both possessed excellent safety profiles and were 16 times more tolerable than amphotericin B.

Epidemiology and subtype distribution of Blastocystis in humans: A review.

Blastocystis is a commonly encountered gastrointestinal protozoan in humans and animals with uncertain pathogenicity. Despite its potential public health impact, epidemiological data regarding the prevalence and molecular subtype (ST) distribution of Blastocystis have been rarely reported. Among Blastocystis STs, ST1-ST4 are common in humans, including healthy and immunodeficient populations. According to the Chi-squared (χ2) association based on the data compiled for this cross-sectional study, the presence of ST1 is associated with asymptomatic infection, whereas the presence of ST4 is associated with symptomatic infection. However, cross-sectional studies cannot clarify the potential pathogenicity of Blastocystis, unlike in vivo and in vitro studies. Poor hygiene, poor sanitation and zoonotic transmission are possible factors associated with high Blastocystis prevalence, although this protozoan may be part of the normal healthy human gastrointestinal microbiota. This review covers the prevalence, STs and distribution of Blastocystis infection in humans. Thus, future epidemiological and subtyping studies could reveal new STs in humans as well as possible associations of STs with disease, drug resistance and related mechanisms such as protease activity. These associations with proper ST identification may facilitate the control of potential threats to host health, including the direct pathogenic effects of Blastocystis or alterations of the gastrointestinal microbiome.

Toys in the Playrooms of Children's Hospitals: A Potential Source of Nosocomial Bacterial Infections?

Pediatric patients are more susceptible and vulnerable to nosocomial infections, in part because of their nascent and developing immune system and in part due to certain congenital conditions. Consequently, we found limited literature that investigated and reported children’s toys in hospital playrooms as potential reservoirs of pathogenic microbes. Hence, in the present study, we aimed to investigate toys as potential vectors for nosocomial infections in children’s hospitals. Microbiological samples from 120 toys were collected between April 2018 and November 2018. The specimens were cultivated on suitable cultivation agars for 24–72 h at 37 °C and CFU/cm2 (colony forming units) was determined. Antibiotic susceptibility testing was performed using disc diffusion and E-tests. Our results indicate that 84% of samples were contaminated with different microbes. Four distinct genera and thirty-seven species of bacteria were identified. The most frequently isolated pathogen was Sphingomonas paucimobilis (>603 CFU/cm2). Most of the identified microorganisms were members of normal human microbiota. Although Staphylococcus aureus and Acinetobacter baumannii were identified, CFU/cm2 was relatively low and they were found to be sensitive to antibiotics. Additionally, plastic toys showed the highest average CFU/cm2 of 91.9. Our results bolster the need for adoption and strict enforcement of proper disinfection techniques for toys in the hospital playrooms.

S3658 Liver, Lung, Brain Abscess 2/2 Strep Intermedius

Introduction: Streptococcus intermedius is a beta-hemolytic, non-motile, catalase-negative, gram-positive member of the Streptococcus anginosus group (SAG) and also a member of normal human microbiota in the respiratory, gastrointestinal, and genitourinary tracts. S. intermedius has a unique tropism in the brain, liver, and lungs leading to abscess formation. Case Description/Methods: A 47-year-old male presented with a 5-day history of nonproductive cough, shortness of breath, pleuritic chest pain and progressively worsening fever/chills. He has a medical history of diabetes mellitus type 2. He denied nausea, vomiting, diarrhea, abdominal pain, headache, recent travel, or recent dental procedures. He denied alcohol use, smoking, and recreational drug use. Vital signs were stable. Labs revealed WBC 27.93, CRP 208, Procalcitonin 1.11, Ferritin 2,568. CT of chest/abdomen/pelvis with contrast revealed a large multiloculated right-sided pleural effusion versus empyema and multiple hepatic abscesses. Prior to broad-spectrum antibiotics the empyema and hepatic abscess were drained and cultures grew streptococcus intermedius and the patient was continued on IV ceftriaxone. On the day of discharge, the patient lost balance while walking and a head CT was obtained which identified multiple basal ganglia and right occipital lesions, with a follow-up MRI brain that confirmed ring-enhancing lesions concerning brain abscesses. These lesions were deemed inaccessible by neurosurgery and then treated as a hematogenous spread of streptococcus intermedius in the setting of recent bacteremia. Follow-up imaging confirmed the lesions to have decreased bin size prior to discharge. Discussion: S. intermedius release pro-inflammatory proteins as well as hydrolytic enzymes such as hyaluronidase and sialidase to induce tissue liquefaction and the formation of pus. S. intermedius is unique to the other bacteria in SAG due to the expression of intermedilysin (ILY), allowing it to cause cell necrosis with membrane bleb formation. The ILY gene is being used as a specific marker to detect S. intermedius via PCR. Risk factors include dental manipulation, sinusitis, diabetes, alcohol use, and malignancy. Treatment is based on susceptibility. An untreated liver abscess may lead to hematogenous spread which increases the risk for mortality. The mortality rate for SAG-associated bacteremia is 10-16%. Early recognition and timely intervention are important for successful treatment and improved outcomes.Figure 1.: One of the multiple hepatic abscess 2/2 strep intermedius.

Exogenous bacterial DnaK increases protein kinases activity in human cancer cell lines

BackgroundStudies of molecular mechanisms underlying tumor cell signaling highlighted a critical role for kinases in carcinogenesis and cancer progression. To this regard, protein kinases regulates a number of critical cellular pathways by adding phosphate groups to specific substrates. For this reason, their involvement in the complex interactions between the human microbiota and cancer cells to determine therapy and tumor progression outcome is becoming increasingly relevant. Mycoplasmas are components of the normal human microbiota, and several species have also been associated to human diseases, including certain cancers. It is also important to note that Mycoplasmas and their proteins are a component of the common tumor microenvironment. In addition, several epidemiological, in vivo and in vitro studies indicate a close involvement of Mycoplasmas in cellular transformation and cancer progression.MethodsIn this study, we investigate the effect of exogenous Mycoplasma DnaK on kinases activity by treating in vitro four different eukaryotic cancer cell lines, namely lung and prostate cancer, colon adenocarcinoma, and neuroblastoma. Phosphorylation of kinases and specific substrates was measured at 20 and 60 min.ResultsKinome analysis of our data indicates that Mycoplasma DnaK promotes the dysregulation of the activity of specific kinases and their substrates, with a known involvement in carcinogenesis and cancer progression.ConclusionsGiven the similarity in structure and amino acid composition of this protein with other bacterial DnaKs we provide a novel mechanism whereby components of the human microbiota and present in the tumor microenvironment are able to deregulate phosphorylation events occurring during carcinogenesis and cancer progression.

Свойства бифидобактерий и использование их в научно-практических целях

Bifidobacteria occupy a special place among various representatives of normal human microbiota. A wide range of probiotic preparations has been obtained based on cultivated strains of various bifidobacteria of the intestinal microbiota. A number of scientific publications noted the immunomodulatory, anticarcinogenic, and antiviral properties of bifidobacteria in vitro and in vivo. Recently, progress has been made in the research and application of this group of microorganisms in genetic engineering. It was established that vaccines against viral and bacterial infections and antitumor substances can be developed on the basis of various strains of bifidobacteria. Bifidobacteria can also be used as adjuvants for other vaccines, as well as delivery systems for biologically active substances to tumors. The prospects for the use of bifidobacteria for the development of recombinant vaccines are discussed. bifidobacteria, medical and biological properties, recombinant vaccines, drug delivery, adjuvants, plasmids This work was funded by the Epidemiology and Microbiology National Research Center. The authors are grateful to V. V. Kuprianov for valuable comments on the text of the review.

Probiotics in Medicine: A Long Debate.

During the last years probiotics gained the attention of clinicians for their use in the prevention and treatment of multiple diseases. Probiotics main mechanisms of action include enhanced mucosal barrier function, direct antagonism with pathogens, inhibition of bacterial adherence and invasion capacity in the intestinal epithelium, boosting of the immune system and regulation of the central nervous system. It is accepted that there is a mutual communication between the gut microbiota and the liver, the so-called “microbiota-gut-liver axis” as well as a reciprocal communication between the intestinal microbiota and the central nervous system through the “microbiota-gut-brain axis.” Moreover, recently the “gut-lung axis” in bacterial and viral infections is considerably discussed for bacterial and viral infections, as the intestinal microbiota amplifies the alveolar macrophage activity having a protective role in the host defense against pneumonia. The importance of the normal human intestinal microbiota is recognized in the preservation of health. Disease states such as, infections, autoimmune conditions, allergy and other may occur when the intestinal balance is disturbed. Probiotics seem to be a promising approach to prevent and even reduce the symptoms of such clinical states as an adjuvant therapy by preserving the balance of the normal intestinal microbiota and improving the immune system. The present review states globally all different disorders in which probiotics can be given. To date, Stronger data in favor of their clinical use are provided in the prevention of gastrointestinal disorders, antibiotic-associated diarrhea, allergy and respiratory infections. We hereby discuss the role of probiotics in the reduction of the respiratory infection symptoms and we focus on the possibility to use them as an adjuvant to the therapeutic approach of the pandemic COVID-19. Nevertheless, it is accepted by the scientific community that more clinical studies should be undertaken in large samples of diseased populations so that the assessment of their therapeutic potential provide us with strong evidence for their efficacy and safety in clinical use.