Human Gastrointestinal Tract Research Articles

Role of Gut Microbial Metabolites in Cardiovascular Diseases-Current Insights and the Road Ahead.

Cardiovascular diseases (CVDs) are the leading cause of premature morbidity and mortality globally. The identification of novel risk factors contributing to CVD onset and progression has enabled an improved understanding of CVD pathophysiology. In addition to the conventional risk factors like high blood pressure, diabetes, obesity and smoking, the role of gut microbiome and intestinal microbe-derived metabolites in maintaining cardiovascular health has gained recent attention in the field of CVD pathophysiology. The human gastrointestinal tract caters to a highly diverse spectrum of microbes recognized as the gut microbiota, which are central to several physiologically significant cascades such as metabolism, nutrient absorption, and energy balance. The manipulation of the gut microbial subtleties potentially contributes to CVD, inflammation, neurodegeneration, obesity, and diabetic onset. The existing paradigm of studies suggests that the disruption of the gut microbial dynamics contributes towards CVD incidence. However, the exact mechanistic understanding of such a correlation from a signaling perspective remains elusive. This review has focused upon an in-depth characterization of gut microbial metabolites and their role in varied pathophysiological conditions, and highlights the potential molecular and signaling mechanisms governing the gut microbial metabolites in CVDs. In addition, it summarizes the existing courses of therapy in modulating the gut microbiome and its metabolites, limitations and scientific gaps in our current understanding, as well as future directions of studies involving the modulation of the gut microbiome and its metabolites, which can be undertaken to develop CVD-associated treatment options. Clarity in the understanding of the molecular interaction(s) and associations governing the gut microbiome and CVD shall potentially enable the development of novel druggable targets to ameliorate CVD in the years to come.

Effectiveness and safety of gut microbiota modification in intestinal diseases. Review

The gut microbiota (GM) is a complex and dynamic community of microorganisms that colonize the human gastrointestinal tract and play an important role in various aspects of the host’s physiology and health. GM is involved in digestion and assimilation of nutrients, synthesis of vitamins and metabolites, modulation of the immune system and defense against pathogens. However, the gut microbiota can also be a source of inflammation and disease when its composition and function are altered. This phenomenon, known as dysbiosis, is associated with almost all gastrointestinal diseases and is most prominent in inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), colorectal cancer, and celiac disease. Considering the important role of GM in the pathogenesis of IBD and other diseases of the gastrointestinal tract, several methods of its modification have been proposed, including the use of probiotics, prebiotics, synbiotics, antibiotics, dietary interventions, fecal microbiota transplantation (FTM) and bacteriophage therapy. However, drawing general conclusions about the efficacy and safety of these approaches is often difficult due to variability in interventions, doses, timing of administration, and the inevitable heterogeneity of host microbiome profiles and gut status. This review presents the results of a large international survey, purposed on the assessment of current practice, preferences, challenges, and expectations of doctors regarding the assessment of the composition of GM and the use of antibiotics, probiotics and TFM in intestinal diseases. The survey was also aimed on the identification of factors influencing the decision‑making process by doctors and barriers limiting the implementation of GM modification in clinical practice. Conclusions drawn from the results of the survey highlight the need for further research, standardization of techniques and evidence‑based recommendations to optimize the use of probiotics, antibiotics and TFM in clinical practice.

Characterization of probiotic strains of Bacillus sp. from fermented palm wine (Nypa fructicans sp.) and exploration of cellulolytic potential for use as an addition in animal feed.

The main objective of this study was to assess cellulolytic probiotic strains from traditional fermented beverages such as palm wine in order to supplement the animal feed and strengthen the gut health of the animal for better digestibility and absorption. In the present study, different types of microbes were isolated from traditionally prepared palm wine and analyzed for their probiotic nature. For any microbe to be probiotic in nature, it has to sustain the harsh conditions of the human gastrointestinal tract such as acid tolerance, bile tolerance at the lower range of pH, and other properties like auto aggregation test, cell surface hydrophobicity test with non-polar hydrocarbons for evaluating its capabilities to adhere to the intestinal cells and antimicrobial nature against pathogens. Bacillus mycoides strain PR04 and Bacillus subtilis strain PR21 were found to be resistant to acid and bile in simulated artificial gastrointestinal tract model, found to be than 55% hydrophobic with xylene and n-hexadecane and also showed antimicrobial activity greater towards pathogenic strains like Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Salmonella typhimurium respectively. The cellulolytic activity of the isolates PR04 and PR21 was evaluated in (0.2-2) % CMC (carboxymethyl cellulose) plate. Bacillus mycoides PR04 and Bacillus subtilis PR21 could degrade carboxymethyl cellulose, filter paper, and sugarcane bagasse. The degradation of sugarcane bagasse was confirmed by Scanning electron microscopy and filter paper degradation after 4days of incubation at 37°C. Cellulase gene of the identified Bacillus sp. strains was amplified by primers CF5'-ACAGGATCCGATGAAAACGGTCAATTTCTATTTT-3' and CR5'-ACTCTCGAGATTGGGTTCTGTTCCCAAT-3'. This study proposes potential probiotic Bacillus mycoides PR04 (Accession no. OR625070) and Bacillus subtilis PR21 (Accession no. OR625072) in the application as an animal feed additive to assist in its digestibility and encourage the gut health.

What if you eat nanoplastics? Simulating nanoplastics fate during gastrointestinal digestion

Despite our growing awareness of micro-and nanoplastics presence in food and beverages, the fate of nanoplastics (NPs) in the human gastrointestinal tract (GIT) remains poorly investigated. Changes of nanoplastics size upon digestive conditions influence the potential of absorption through the intestine. In this study, polymer nanoparticles with different physicochemical properties (size, surface and chemistry) were submitted to gastrointestinal digestion (GID) simulated in vitro. Their agglomeration behaviour was measured with a unique set of analytical approaches, allowing to study NPs’ interactions with the digestive enzymes. Smaller NPs agglomerated more, narrowing the overall particle size distribution of smaller and larger NPs. NPs of different polymers exhibited heteroagglomeration. Digestive enzymes interact with the NPs, forming large but fragile agglomerates. In presence of the enzymes, even acid-functionalized NPs, typically stable in harsh conditions, agglomerated similarly to the non-functionalized PS NPs. These results highlight the role of the GID in increasing the effective size of ingested NPs, potentially reducing their ability to pass through the cell membranes. Our findings address a critical knowledge gap in nanoplastics oral uptake potential, providing a solid technical foundation for their characterization.

Metalloproteomics Reveals Multi-Level Stress Response in Escherichia coli When Exposed to Arsenite.

The arsRBC operon encodes a three-protein arsenic resistance system. ArsR regulates the transcription of the operon, while ArsB and ArsC are involved in exporting trivalent arsenic and reducing pentavalent arsenic, respectively. Previous research into Agrobacterium tumefaciens 5A has demonstrated that ArsR has regulatory control over a wide range of metal-related proteins and metabolic pathways. We hypothesized that ArsR has broad regulatory control in other Gram-negative bacteria and set out to test this. Here, we use differential proteomics to investigate changes caused by the presence of the arsR gene in human microbiome-relevant Escherichia coli during arsenite (AsIII) exposure. We show that ArsR has broad-ranging impacts such as the expression of TCA cycle enzymes during AsIII stress. Additionally, we found that the Isc [Fe-S] cluster and molybdenum cofactor assembly proteins are upregulated regardless of the presence of ArsR under these same conditions. An important finding from this differential proteomics analysis was the identification of response mechanisms that were strain-, ArsR-, and arsenic-specific, providing new clarity to this complex regulon. Given the widespread occurrence of the arsRBC operon, these findings should have broad applicability across microbial genera, including sensitive environments such as the human gastrointestinal tract.

Causal Relationship Between Gut Microbiota and Leukemia: Future Perspectives.

The gut microbiota plays a crucial role in maintaining homeostasis in the human gastrointestinal tract. Numerous studies have shown a strong association between the gut microbiota and the emergence and progression of various diseases. Leukemia is one of the most common hematologic malignancies. Although standardized protocols and expert consensus have been developed for routine diagnosis and treatment, limitations remain due to individual differences. Nevertheless, a large number of studies have established a link between the gut microbiota and leukemia, with disturbances in the gut microbiota directly or indirectly affecting the development of leukemia. However, the causal relationship between the two remains unclear, and studying and exploring the causal relationship may open up entirely new avenues and protocols for use in the prevention and/or treatment of leukemia, offering new insights into diagnosis and treatment. In this review, the intricate relationship between the gut microbiota and leukemia is explored in depth, including causal associations, metabolite effects, therapeutic applications, and complications. Based on the characteristics of the gut microbiota, the future applications and prospects of gut microbiota are discussed to provide useful information for clinical treatment of leukemia.

Diverse Sources and Latent Reservoirs of Community-Associated Clostridioides difficile Infection.

Clostridioides difficile (C. difficile) is a spore-forming, toxin-producing, anaerobic bacterium infecting the human gastrointestinal tract, causing diarrhea and life-threatening colitis. C. difficile epidemiology continues to evolve, and it is recognized as a major community-associated pathogen in addition to its established role in causing healthcare-associated infection. While current surveillance and prevention measures mainly focus on healthcare-associated C. difficile infections, much less is known about the factors driving community-associated C. difficile infections. This review highlights the potential contribution of reservoirs, including asymptomatic carriers, to community-associated C. difficile transmission. The reservoirs discussed in this review provide potential avenues for research to better understand and reduce community-associated transmission of C. difficile.

Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease.

Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum. Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry. Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients. IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

A Comprehensive Review of the Triangular Relationship among Diet-Gut Microbiota-Inflammation.

The human gastrointestinal tract hosts a complex and dynamic community of microorganisms known as the gut microbiota, which play a pivotal role in numerous physiological processes, including digestion, metabolism, and immune function. Recent research has highlighted the significant impact of diet on the gut microbiota composition and functionality, and the consequential effects on host health. Concurrently, there is growing evidence linking the gut microbiota to inflammation, a key factor in many chronic diseases such as inflammatory bowel disease (IBD), obesity, diabetes, and cardiovascular diseases (CVDs). This review explores how dietary components influence the gut microbiota composition, how these microbial changes affect inflammatory pathways, and the therapeutic implications of modulating this axis for chronic inflammatory disease prevention and management. Beneficial dietary patterns, such as the Mediterranean diet (MD) and plant-based diets, promote a diverse and balanced gut microbiota composition, supporting anti-inflammatory pathways. Conversely, the Western diet (WD), high in saturated fats and refined sugars, is associated with dysbiosis and increased inflammation. With all the links between the three variables considered, this review attempts to offer a thorough examination of the triangle formed by inflammation, the gut microbiota, and food.

Application of <i>in vitro</i> studies to predict the pharmacokinetics of rivaroxaban tablets

Introduction. The most important stage of pharmaceutical development of a generic drug is a clinical trial involving humans – a bioequivalence study. Considering the importance of finding rivaroxaban drugs in the list of vital and essential drugs, as part of ensuring technological sovereignty, the use of scientific robust and effective methods for determining the quality of the dosage form is required.Aim. Conduct a study of rivaroxaban tablets on a physiologically relevant tester to predict pharmacokinetic profiles.Materials and methods. The objects of the study are "Xarelto®, film-coated tablets, 10 mg" (series BXJS871, with an expiration date of October 31, 2024, Bayer AG, Germany), "Xarelto®, film-coated tablets, 20 mg" (series BXKDF32, with an expiration date of May 17, 2026, Bayer AG, Germany) and "Rivaroxaban, film-coated tablets, 10 mg" and "Rivaroxaban, film-coated tablets, 20 mg", domestically produced, with valid expiration dates. During the study, reagents were used to prepare dissolution media and perform quantitative determination. The physiologically relevant test was performed on the SC PRT-6 device (LLC "Scientific Compliance", Russia). The quantitative content of released rivaroxaban within the comparative dissolution kinetics test in a medium of 0.1 in a medium of 0.1 % sodium lauryl sulfate solution in a phosphate buffer solution pH 6.5 was carried out on a SF-2000 spectrophotometer (LLC "OKB Spektr", Russia). The quantitative content of released rivaroxaban within the comparative dissolution kinetics test in biorelevant dissolution media and physiological relevance test was assessed on a high-performance liquid chromatograph "Chromatec-Crystal HPLC 2014" (CJSC "Chromatec", Russia). Pharmacokinetic profiles were modeled in the PK-Sim® (Systems Biology Software Suite 11.2, Bayer Technology Services GmbH, Germany) program based on the data obtained within the physiologically relevant test. The clinical study of rivaroxaban tablets was a prospective, open-label, randomized, crossover, two-stage comparative study in two groups of volunteers with a single dose of drugs on the fast condition. The study randomized 30 healthy male volunteers aged 18–45 years.Results and discussion. A complex of in vitro tests was conducted, profiles were obtained that allow us to evaluate the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. A comparison of the sequential and hybrid schemes for conducting the physiological relevance test was carried out. Within the framework of the set of tests, qualitative and quantitative correlation with the clinical trials data was observed only for the hybrid physiological relevance test scheme. Based on the results of physiological relevance test using different schemes, pharmacokinetic profiles for a pair of drugs were predicted and the prediction error was assessed.Conclusion. A set of scientific in vitro tests was conducted for the drugs "Xarelto®, film-coated tablets, 10 mg and 20 mg", "Rivaroxaban, film-coated tablets, 10 mg and 20 mg". Based on the physiological relevance test results, pharmacokinetic profiles for a pair of drugs were predicted with low error and high reliability. As part of the comparison of data obtained during clinical trial and modeling, the smallest prediction error was noted when performing physiological relevance test using a hybrid scheme.

The SaeRS two-component system regulates virulence gene expression in group B Streptococcus during invasive infection.

Group B Streptococcus (or GBS) is a normal inhabitant of the human gastrointestinal and genital tracts that can also cause deadly infections in newborns and elderly people. The transition from a harmless commensal to a dangerous pathogen relies on the timely expression of bacterial molecules necessary for causing disease. In this study, we characterize the two-component system SaeRS as a key regulator of such virulence factors. Our analysis reveals a specialized regulatory system that is activated only during infection to dynamically adjust the production of two virulence factors involved in interactions with host cells. Overall, our findings highlight the critical role of SaeRS in GBS infections and suggest that targeting this system may be useful for developing new antibacterial drugs.

The Role of Fecal Microbiota Transplantation (FMT) in the Management of Metabolic Diseases in Humans: A Narrative Review.

The gut microbiota represents a complex ecosystem of trillions of microorganisms residing in the human gastrointestinal tract, which is known to interact with the host physiology and regulate multiple functions. Alterations in gut microbial composition, diversity, and function are referred to as dysbiosis. Dysbiosis has been associated with a variety of chronic diseases, including Clostridioides difficile infections, but also cardiometabolic diseases, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM). The implication of gut microbiota dysbiosis in the pathogenesis of both obesity and T2DM has paved the way to implementing novel therapeutic approaches for metabolic diseases through gut microbial reconfiguration. These interventions include probiotics, prebiotics, and synbiotics, while a more innovative approach has been fecal microbiota transplantation (FMT). FMT is a procedure that delivers healthy human donor stool to another individual through the gastrointestinal tract, aiming to restore gut microbiota balance. Several studies have investigated this approach as a potential tool to mitigate the adverse metabolic effects of gut microbiota aberrations associated with obesity and T2DM. The aim of the present review was to critically summarize the existing evidence regarding the clinical applications of FMT in the management of obesity and T2DM and provide an update on the potential of this method to remodel the entire host microbiota, leading thus to weight loss and sustained metabolic benefits. Safety issues, long-term efficacy, limitations, and pitfalls associated with FMT studies are further discussed, emphasizing the need for further research and standardization in certain methodological aspects in order to optimize metabolic outcomes.

Performing a physiologically relevant test for cladribine tablets

Introduction. The introduction of devices – analogues of GIS (hereinafter–- Gastro-intestinal simulator) is one of the current ways to develop in-vitro assessment of the quality of solid dosage forms. Testing on a physiologically relevant test device (hereinafter referred to as PRT) makes it possible to predict pharmacokinetic profiles due to more relevant conditions, including the use of biorelevant dissolution media, physiological volumes of the gastrointestinal tract, as well as transit between them.Aim. Conduct a study of cladribine tablets on a physiologically relevant tester in order to predict the behavior of the drug in the human gastrointestinal tract.Materials and methods. The objects of the study are "Mavenclad®, tablets, 10 mg" (series 2200754, expiration date until 04.2025, NERPHARMA, S.r.L., Italy) and "Cladribine, tablets, 10 mg" of domestic production with valid expiration date. During the study, the reagents necessary for the preparation of biorelevant dissolution media and quantitative determination by HPLC. Physiologically relevant test were carried out using an apparatus of our own production, consisting of a DT-6 dissolution tester (ERWEKA GmbH, Germany), a water bath equipped with a Thermomix WB-4 heating element (B. Braun, Germany), and peristaltic pumps (Kamoer, China). The quantitative content of released cladribine was assessed using a highly efficient liquid chromatograph "Khromatek-Kristall HPLC 2014" (ZAO SKB "Khromatek", Russia) using a validated method at a wavelength of 252 nm, analysis time – 7 min, column – Grace HPLC Column Platinum C18-EPS, 250 × 4.6 mm, 5 mm (Grace, USA), temperature – 35 °C, elution mode – isocratic (A : B 80 : 20), mobile phase A – 0.1 % H3PO4 solution, phase B – acetonitrile.Results and discussion. Profiles were obtained to assess the dynamics and degree of release of the studied drugs in various parts of the human gastrointestinal tract. Despite the expected degradation of cladribine in an acidic environment (pH1.2), under physiologically relevant conditions, the drug reached the third section (small intestine model) without degradation. Complete release of cladribine from the test and reference dosage forms was observed. Also, in the future, based on the data obtained, it is possible to predict pharmacokinetic profiles using physiologically based pharmacokinetic modeling approaches.Conclusion. A PSF study was conducted for the drugs "Mavenclad®, tablets, 10 mg" and "Cladribine, tablets, 10 mg". Quantitative determination was carried out by HPLC-UV method. The test results showed complete release of both drugs and reaching the intestinal tract, indicating the absence of degradation of cladribine in the region simulating the stomach.

Candida species-specific colonization in the healthy and impaired human gastrointestinal tract as simulated using the Mucosal Ileum-SHIME® model.

Candida species primarily exist as harmless commensals in the gastrointestinal tract of warm-blooded animals. However, they can also cause life-threatening infections, which are often associated with gut microbial dysbiosis. Identifying the microbial actors that restrict Candida to commensalism remains a significant challenge. In vitro models could enable a mechanistic study of the interactions between Candida and simulated colon microbiomes. Therefore, this study aimed to elucidate the spatial and temporal colonization kinetics of specific Candida, including C. albicans, C. tropicalis, and C. parapsilosis, and their relative Nakaseomyces glabratus, by using an adapted SHIME® model, simulating the ileum, and proximal and distal colons. We monitored fungal and bacterial colonization kinetics under conditions of eubiosis (commensal lifestyle) and antibiotic-induced dysbiosis (pathogenic lifestyle). Our findings highlighted the variability in the colonization potential of Candida species across different intestinal regions. The ileum compartment proved to be the most favourable environment for C. albicans and C. parapsilosis under conditions of eubiosis. Antibiotic-induced dysbiosis resulted in resurgence of opportunistic Candida species, especially C. tropicalis and C. albicans. Future research should focus on identifying specific bacterial species influencing Candida colonization resistance and explore the long-term effects of antibiotics on the mycobiome and bacteriome.

The microbiota: a crucial mediator in gut homeostasis and colonization resistance.

The gut microbiota is a complex and diverse community of microorganisms that colonizes the human gastrointestinal tract and influences various aspects of human health. These microbes are closely related to enteric infections. As a foreign entity for the host, commensal microbiota is restricted and regulated by the barrier and immune system in the gut and contributes to gut homeostasis. Commensals also effectively resist the colonization of pathogens and the overgrowth of indigenous pathobionts by utilizing a variety of mechanisms, while pathogens have developed strategies to subvert colonization resistance. Dysbiosis of the microbial community can lead to enteric infections. The microbiota acts as a pivotal mediator in establishing a harmonious mutualistic symbiosis with the host and shielding the host against pathogens. This review aims to provide a comprehensive overview of the mechanisms underlying host-microbiome and microbiome-pathogen interactions, highlighting the multi-faceted roles of the gut microbiota in preventing enteric infections. We also discuss the applications of manipulating the microbiota to treat infectious diseases in the gut.

The Potential Role of Butyrate in the Pathogenesis and Treatment of Autoimmune Rheumatic Diseases.

The gut microbiota is a complex ecosystem of microorganisms residing in the human gastrointestinal tract, playing a crucial role in various biological processes and overall health maintenance. Dysbiosis, an imbalance in the composition and function of the gut microbiota, is linked to systemic autoimmune diseases (SAD). Short-chain fatty acids (SCFAs), especially butyrate, produced by the gut microbiota through the fermentation of dietary fibers, play a significant role in immunomodulation and maintaining intestinal homeostasis. Butyrate is essential for colonocyte energy, anti-inflammatory responses, and maintaining intestinal barrier integrity. Studies show reduced butyrate-producing bacteria in SAD patients, suggesting that increasing butyrate levels could have therapeutic benefits. Butyrate's anti-inflammatory effects and its potential therapeutic role have been studied in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, systemic sclerosis, and Behçet's disease. Despite promising in vitro and animal model results, human studies are limited, and the optimal strategies for modulating dysbiosis in SADs remain elusive. This review explores the current evidence on the immunoregulatory role of butyrate and its potential therapeutic effects in SAD.

A Review of Whey Protein-Based Bioactive Delivery Systems: Design, Fabrication, and Application.

The efficacy of many edible bioactive agents is limited by their low water dispersibility and chemical instability in foods, as well as by their poor bioaccessibility, low absorption, and metabolism within the human gastrointestinal tract. Whey proteins are amphiphilic molecules that can be used to construct a variety of edible carrier systems that can improve the performance of bioactive ingredients. These carrier systems are being used by the food and biomedical industries to encapsulate, protect, and deliver a variety of bioactive agents. In this article, we begin by providing an overview of the molecular and functional characteristics of whey proteins, and then discuss their interactions with various kinds of bioactive agents. The ability of whey proteins to be used as building blocks to assemble different kinds of carrier systems is then discussed, including nanoparticles, hydrogels, oleogels, bigels, nanofibers, nanotubes, and nanoemulsions. Moreover, applications of these carrier systems are highlighted. Different kinds of whey protein-based carriers can be used to encapsulate, protect, and deliver bioactive agents. Each kind of carrier has its own characteristics, which make them suitable for different application needs in foods and other products. Previous studies suggest that whey protein-based carriers are particularly suitable for protecting chemically labile bioactive agents and for prolonging their release profiles. In the future, it is likely that the applications of whey protein-based carriers in the food and pharmaceutical fields will expand.

Synergid activity of lysozyme and carnosine with antimicrobial drugs in relation to Klebsiella pneumoniae

Klebsiella pneumoniae strains are opportunistic microorganisms that colonize the human gastrointestinal tract and can spread to various tissues and systems of the body, causing a wide range of severe diseases, including pneumonia. The problem of Klebsiella infections has become topical recently due to the spread of hypervirulent and antibiotic-resistant strains in the K. pneumoniae population, which indicated the need to develop modern antimicrobial agents. One of the approaches to combating pathogens of pneumonia is a combination of lysozyme with antimicrobial drugs, which was successfully tested in children’s hospitals in Orenburg. A natural antioxidant and antioxidant, carnosine, is considered as a new candidate in the fight against Klebsiella. A synergistic combination of carnosine with antimicrobial agents against Klebsiella pneumoniae was established in vitro. The results obtained allowed us to expand the range of effective and safe means of combating pathogens of Klebsiella infections.

Bacteremia caused by Desulfovibrio desulfuricans with the intestinal tract as the portal of entry: two case reports and a literature review

BackgroundDesulfovibrio desulfuricans (D. desulfuricans), a commensal anaerobic gram-negative rod endemic to the soil environment and human gastrointestinal tract, rarely causes bloodstream infections. We report two rare cases of bacteremia caused by D. desulfuricans in which the intestinal tract was the portal of entry. In addition, we summarize findings on D. desulfuricans.Case presentationCase 1: A 51-year-old man presented to the emergency department with the chief complaints of fever and right lower abdominal pain. He was admitted to the hospital with ascending colonic diverticulitis and received empirical antibacterial therapy with piperacillin/tazobactam. Blood culture revealed D. desulfuricans. The patient was discharged after 2 weeks of antimicrobial therapy. Case 2: A 95-year-old woman presented to our hospital with a chief complaint of fever. Owing to an elevated inflammatory response and pyuria, the patient was diagnosed with pyelonephritis and treated with ceftriaxone. Klebsiella pneumoniae was detected in her urine culture, while D. desulfuricans was detected in her blood culture. The patient was then treated with ampicillin/sulbactam for 14 days. The fecal occult blood test result was positive, suggesting a colonic mucosal lesion, such as a malignant tumor, may have been the portal of entry for D. desulfuricans bacteremia. Previous literature reviews indicate that D. desulfuricans bacteremia often results from liver or renal abscesses, intestinal lesions, among others, serving as the portal of entry. Although no specific underlying disease has been reported, it is more common in the older population. We encountered two cases of D. desulfuricans bacteremia and combined them with 15 cases from previous studies to explore the characteristics of the disease. The proportion of patients aged \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\ge\\:$$\\end{document}60 years was 73.7%; overall, 73.7% had gastrointestinal complications, and 63.2% had abdominal symptoms at the time of presentation.ConclusionsWe encountered two rare cases of D. desulfurican bacteremia. This type of bacteremia is more common in elderly people over 60 years of age and is often associated with hepatobiliary and gastrointestinal diseases.

Functional prediction and assignment of Clostridium botulinum type A1 operome: A quest for prioritizing drug targets

Clostridium botulinum strain Hall produces potent botulinum neurotoxin type A1, which causes food-borne, infant, and wound botulism in humans. Antibiotics and botulinum antitoxins can control growth and prevent botulinum toxicity. However, limited information on a protein with an unknown function hinders the discovery of new drug targets for this disease. In this study, a combined bioinformatics approach with literature support was applied to predict, assign, and validate operome functions. Our functional annotation scheme was based on sequence motifs, conserved domains, structures, protein folds, and evolutionary relationships. Approximately 14.62 % of the operome exhibited sequence similarity to known proteins, with 6.65 % predicted functions for 293 proteins, including 121 proteins exclusive to C. botulinum. Structural analysis revealed a significant presence of the Rossmann fold (26 %) and miscellaneous folds (43 %) among the operome. Transporters (>85) and transcriptional regulators (>45) were prevalent, underscoring their importance in C. botulinum adaptive strategies. The newly identified operome contributed to the diverse cellular and metabolic processes of this organism. The function of its operome was involved in amino acid metabolism and botulinum neurotoxin biosynthesis. In this study, we identified and characterized 13 new virulence proteins from the operome to determine their structure–function relationships. These new metabolic and virulence proteins allow the organism to colonize and interact with the human gastrointestinal tract. This study provides a quest for new drugs and targets for treating the underlying diseases of C. botulinum in humans.