The spread of multidrug-resistant Escherichia coli in healthcare facilities is a global challenge. Hospital-acquired infections produced by Escherichia coli include gastrointestinal, blood-borne, urinary tract, surgical sites, and neonatal infections. Therefore, novel approaches are needed to deal with this pathogen and its rising resistance. The concept of attenuating virulence factors is an alternative strategy that might lead to low levels of resistance and combat this pathogen. A sub-inhibitory concentration (1⁄4 MIC) of sitagliptin and nitazoxanide was used for phenotypic assessments of Escherichia coli virulence factors such as biofilm production, swimming motility, serum resistance, and protease production. Moreover, qRT-PCR was used to determine the impact of sub-MIC of the tested drugs on the relative expression levels of papC, fimH, fliC, kpsMTII, ompT_m, and stcE genes encoding virulence factors in Escherichia coli. Also, an in vivo model was conducted as a confirmatory test. Phenotypically, our findings demonstrated that the tested strains showed a significant decrease in all the tested virulence factors. Moreover, the genotypic results showed a significant downregulation in the relative expression levels of all the tested genes. Besides, the examined drugs were found to be effective in protecting mice against Escherichia coli pathogenesis. Sitagliptin and nitazoxanide exhibited strong anti-virulence activities against Escherichia coli. In addition, it is recommended that they might function as adjuvant in the management of Escherichia coli infections with either conventional antimicrobial agents or alone as alternative treatment measures.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Biofilms drug effects MeSH
- Nitro Compounds MeSH
- Escherichia coli * drug effects pathogenicity genetics MeSH
- Virulence Factors genetics metabolism MeSH
- Escherichia coli Infections * drug therapy microbiology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial MeSH
- Mice MeSH
- Escherichia coli Proteins genetics MeSH
- Sitagliptin Phosphate * pharmacology MeSH
- Thiazoles * pharmacology MeSH
- Virulence drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.
- MeSH
- Dysbiosis metabolism MeSH
- Blood-Brain Barrier metabolism MeSH
- Humans MeSH
- Brain * metabolism MeSH
- Neurodegenerative Diseases * microbiology metabolism MeSH
- Brain-Gut Axis * physiology MeSH
- Probiotics MeSH
- Aging * MeSH
- Gastrointestinal Microbiome * physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Narušení mikrobiálního ekosystému člověka představuje významný patogenetický faktor řady onemocnění. Již několik desetiletí je známa úloha alterace střevní mikrobioty v patogenezi rekurentní klostridiové kolitidy. Závažné narušení ve složení nebo funkci mikrobioty (mluvíme o tzv. dysbióze) je dnes nicméně popisováno i v patogenezi dalších chorobných stavů. V tomto smyslu jsou nejčastěji uváděny idiopatické střevní záněty, syndrom dráždivého tračníku, diabetes mellitus 2. typu, roztroušená skleróza, Parkinsonova nemoc, dále také např. jaterní encefalopatie u pacientů s cirhózou jater. Terapeuticky zasáhnout na úrovni poškozené střevní mikrobioty se snažíme různými způsoby. Velmi nadějně se jeví metoda mající za cíl dosáhnout obnovy přirozené mikrobiální homeostázy v tlustém střevě pomocí stolice od zdravého dárce, která je přenesena do zažívacího traktu nemocného. Pro tuto metodu se u nás vžil název "fekální bakterioterapie". V zahraniční literatuře se nejčastěji setkáváme s označením "Fecal Microbiota Transplantation" či se zkratkou FMT.
Disruption of the human microbial ecosystem represents a significant pathogenic factor of many diseases. The role of altered intestinal microbiota in the pathogenesis of recurrent Clostridium difficile colitis has been known for decades. Still, severe disruptions in the composition or function of the microbiota (we are speaking about dysbiosis) is nowadays also described in the pathogenesis of other pathological conditions. In this sense, the most commonly listed are idiopathic inflammatory bowel diseases, irritable bowel syndrome, type 2 diabetes mellitus, multiple sclerosis, Parkinson's disease, furthermore, for example, hepatic encephalopathy in patients with liver cirrhosis. We try to therapeutically intervene on the level of damaged intestinal microbiota in various ways. One very promising method seeks to restore natural microbial homeostasis in the colon using stool from a healthy donor, which is transferred into the digestive tract of the patient. For us, this method became commonly known as "fecal bacteriotherapy". The international literature typically uses the term "Fecal Microbiota Transplantation" or by the abbreviation FMT.
- MeSH
- Drug Resistance, Bacterial MeSH
- Dysbiosis * therapy MeSH
- Fecal Microbiota Transplantation * statistics & numerical data trends MeSH
- Inflammatory Bowel Diseases therapy MeSH
- Humans MeSH
- Central Nervous System Diseases therapy MeSH
- Enterocolitis, Pseudomembranous prevention & control therapy MeSH
- Gastrointestinal Microbiome physiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
PURPOSE OF REVIEW: The immunological processes that lead to multiple sclerosis (MS) and occur during the progressive phase of the disease are manifold and still not well understood. This review summarizes new insights on this topic that were gained through recent studies with diverse scientific approaches. RECENT FINDINGS: While genetic risk clearly contributes to MS, external factors play a key role in its pathogenesis as well. Epstein-Barr virus infection correlates significantly with MS risk and seems to be a major causal factor. Even though our knowledge on the human gut microbiome and its connection to the central nervous system is far from being complete, several studies have proven that the gut-brain axis influences neuroinflammation and disease progression in MS. It has become much clearer that MS is not solely a T cell-mediated disease but is also strongly driven by B cells and pathogenic antibodies. Beyond the peripheral immune cells, glial cells and their interactions with neurons are important players contributing to disease activity and progression in MS. SUMMARY: Taken together, recent publications on immunological processes in the context of MS implicate a multitude of noncanonical mechanisms that need to be further explored regarding their interplay and contribution to the degenerative course of the disease.
BACKGROUND/OBJECTIVES: Crohn's disease is known for being associated with an abnormal composition of the bacterial flora, dysbiosis and intestinal function disorders. Metabolites produced by gut microbiota play a pivotal role in the pathogenesis of CD, and the presence of unspecific extraintestinal manifestations. METHODS: The aim of this study was a determination of the level of bacterial metabolites in blood plasma in patients with Crohn's disease. CD patients (29) and healthy individuals (30) were recruited for this study. Bacterial metabolites (SCFAs and TMAO panel) were measured by a liquid chromatography-mass spectrometry system. RESULTS: A significant correlation (p-value < 0.05) between CD and bacterial metabolites was obtained for three of eight tested SCFAs; acetic acid (reduced in CD; FC 1.7; AUC = 0.714), butyric acid (increased; FC 0.68; AUC = 0.717), 2MeBA (FC 1.168; AUC = 0.702), and indoxyl (FC 0.624). The concentration of CA (FC 0.82) and choline (FC 0.78) in plasma was significantly disturbed according to the biological treatment. Choline level (FC 1.28) was also significantly disturbed in the patients treated with glucocorticoids. In total, 68.97% of Crohn's patients presented extraintestinal manifestations (EIMs) of Crohn's disease, mainly osteoarticular complications. The level of BA was statistically significantly elevated in patients with extraintestinal (FC 0.602) manifestations, while in the group of patients with osteoarticular complications, a significant difference in the level of betaine (FC 1.647) was observed. CONCLUSIONS: The analyzed bacterial metabolites of plasma may significantly help in the diagnostic process, and in the monitoring of the disease course and treatment, in a lowly invasive way, as biomarkers after additional research on a larger group of patients.
- MeSH
- Bacteria MeSH
- Biomarkers blood MeSH
- Choline blood MeSH
- Crohn Disease * blood microbiology MeSH
- Adult MeSH
- Dysbiosis blood microbiology MeSH
- Fatty Acids, Volatile blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Methylamines blood MeSH
- Young Adult MeSH
- Gastrointestinal Microbiome * MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Ateroskleróza je hlavnou prí činou kardiovaskulá rnych ochorení a významne prispieva k celosvetovej úmrtnosti. Stá le rastúci počet dôkazov naznačuje, že črevný mikrobióm môže zohrá vať kľúčovú úlohu v patogenéze tohto ochorenia. Črevný mikrobióm pozostá va z biliónov mikroorganizmov, ktoré nielen podporujú trá venie a metabolizmus, ale tiež ovplyvňujú imunitnú odpoveď hostiteľa. Zmeny v zložení črevného mikrobiómu boli spojené s rôznymi chronickými ochoreniami, vrá tane obezity, cukrovky a aterosklerózy. Tento člá nok poskytuje stručný prehľad zloženia črevného mikrobiómu u pacientov s koroná rnou chorobu srdca a sumarizuje možné zá kladné mechanizmy vplyvu na rozvoj aterosklerózy. Zloženie črevného mikrobiómu u pacientov s aterosklerózou sa líš i od zdravých jedincov. Identifiká cia a pochopenie týchto rozdielov poskytuje nové možnosti pre diagnostiku a liečbu aterosklerózy.
Atherosclerosis is a major cause of cardiovascular diseases and significantly contributes to global mortality. An increasing body of evidence suggests that the gut microbiome may play a key role in the pathogenesis of this disease. The gut microbiome consists of trillions of microorganisms that not only support digestion and metabolism but also influence the host's immune response. Alterations in the composition of the gut microbiome have been associated with various chronic diseases, including obesity, diabetes, and atherosclerosis. This article provides a brief overview of the gut microbiome composition in patients with coronary artery disease and summarizes the potential underlying mechanisms influencing the development of atherosclerosis. The composition of the gut microbiome in patients with atherosclerosis differs from that in healthy individuals. Identifying and understanding these differences offers new opportunities for the diagnosis and treatment of atherosclerosis.
- MeSH
- Arteriosclerosis * etiology prevention & control MeSH
- Humans MeSH
- Gastrointestinal Microbiome * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Heterogeneous cancers that lack strong driver mutations with high penetrance, such as head and neck squamous cell carcinoma (HNSCC), present unique challenges to understanding their aetiology due to the complex interactions between genetics and environmental factors. The interplay between lifestyle factors (such as poor oral hygiene, smoking, or alcohol consumption), the oral and gut microbiome, and host genetics appears particularly important in the context of HNSCC. The complex interplay between the gut microbiota and cancer treatment outcomes has also received increasing attention in recent years. This review article describes the bidirectional communication between the host and the oral/gut microbiome, focusing on microbiome-derived metabolites and their impact on systemic immune responses and the modulation of the tumour microenvironment. In addition, we review the role of host lifestyle factors in shaping the composition of the oral/gut microbiota and its impact on cancer progression and therapy. Overall, this review highlights the rationality of considering the oral/gut microbiota as a critical determinant of cancer therapy outcomes and points to therapeutic opportunities offered by targeting the oral/gut microbiota in the management of HNSCC.
- MeSH
- Squamous Cell Carcinoma of Head and Neck * microbiology pathology immunology therapy MeSH
- Humans MeSH
- Tumor Microenvironment * immunology MeSH
- Head and Neck Neoplasms * immunology microbiology pathology therapy MeSH
- Gastrointestinal Microbiome * immunology MeSH
- Life Style MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Gram-positive bacteria are responsible for a wide range of infections in humans. In most Gram-positive bacteria, sortase A plays a significant role in attaching virulence factors to the bacteria's cell wall. These cell surface proteins play a significant role in virulence and pathogenesis. Even though antibiotics are available to treat these infections, there is a continuous search for an alternative strategy due to an increase in antibiotic resistance. Thus, using anti-sortase drugs to combat these bacterial infections may be a promising approach. Here, we describe a method for targeting Gram-positive bacterial infection by combining curcumin and trans-chalcone as sortase A inhibitors. We have used curcumin and trans-chalcone alone and in combination as a sortase A inhibitor. We have seen ~78%, ~43%, and ~94% inhibition when treated with curcumin, trans-chalcone, and a combination of both compounds, respectively. The compounds have also shown a significant effect on biofilm formation, IgG binding, protein A recruitment, and IgG deposition. We discovered that combining curcumin and trans-chalcone is more effective against Gram-positive bacteria than either compound alone. The present work demonstrated that a combination of these natural compounds could be used as an antivirulence therapy against Gram-positive bacterial infection.
- MeSH
- Aminoacyltransferases * antagonists & inhibitors metabolism MeSH
- Anti-Bacterial Agents * pharmacology chemistry MeSH
- Bacterial Proteins * metabolism antagonists & inhibitors MeSH
- Biofilms * drug effects MeSH
- Chalcone * pharmacology chemistry MeSH
- Cysteine Endopeptidases * metabolism MeSH
- Virulence Factors metabolism MeSH
- Gram-Positive Bacterial Infections drug therapy microbiology MeSH
- Gram-Positive Bacteria drug effects MeSH
- Curcumin * pharmacology chemistry MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Virulence drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Role některých konkrétních bakterií, jako je např. Helicobacter pylori, v etiologii a patogenezi lymfomu je již dlouho známá, ale v posledních letech se ukazuje význam mikrobiomu (tvořen 1013 až 1018 mikroby, které osidlují lidské tělo). Vliv celého mikrobiomu spočívá v regulaci imunitního systému ať přímým působením, nebo prostřednictvím produkovaných metabolitů. Z přibývajících dat vyplývá, že složení střevní mikrobioty se podílí na celé řadě onemocnění včetně nádorových. U pacientů s hematologickými malignitami je často pozorována snížená druhová diverzita a rozdílné složení mikrobioty oproti zdravým kontrolám. Některé bakterie jsou také spojovány s komplikacemi či s odpovědí na léčbu. Význam těchto bakterií roste zejména s širším použitím imunoterapie, v jejíž efektivitě hraje důležitou roli funkční imunitní systém. V následujících řádcích se zaměřujeme na úlohu střevní mikrobioty v etiologii a v patogenezi hematologických malignit a také na jeho roli v ovlivnění protinádorové terapie u těchto nádorů.
The role of particular bacteria such as Helicobacter pylori in the etiology and pathogenesis of lymphoma has been well known, but in recent years the importance of the microbiome complex (made up of 1013 to 1018 microbes that inhabit the human body) has also become apparent. Its effect is mediated by the regulation of the immune system, either by direct action or through produced metabolites. Accumulating data suggest that the composition of the gut microbiota impacts a wide range of diseases, including cancer. Patients with hematological malignancies often show reduced species diversity and different microbiota composition compared to healthy controls. Some bacteria are also associated with complications or response to treatment. Nowadays, the importance of the microbial effect is increasing, particularly with the wider use of immunotherapy, where the treatment efficacy relays on a functional immune system. In this review, we focus on the role of the gut microbiota in the etiology and pathogenesis of hematological malignancies and its role in impacting anticancer therapy.
- MeSH
- Precursor Cell Lymphoblastic Leukemia-Lymphoma microbiology MeSH
- Receptors, Chimeric Antigen therapeutic use MeSH
- Hematologic Neoplasms * microbiology MeSH
- Transplantation, Homologous MeSH
- Immune Checkpoint Inhibitors therapeutic use MeSH
- Humans MeSH
- Multiple Myeloma microbiology MeSH
- Antineoplastic Agents, Immunological therapeutic use MeSH
- Gastrointestinal Microbiome * MeSH
- Check Tag
- Humans MeSH
Súhrn: Hidradenitis suppurativa (HS) je chronický imunitne mediovaný zápal pilosebaceóznej jednotky a apokrinných potných žliaz s tvorbou bolestivých uzlov, abscesov, hnisajúcich fistúl a jaziev predilekčne v intertiginóznych priestoroch. U pacientov s HS je zvýšená incidencia zápalových ochorení čreva (IBD – inflammatory bowel disease), čo poukazuje na ich vzájomné priesečníky v patogenéze dysregulácie vrodenej a adaptívnej imunity. Nedávno sa výrazne zvýšil záujem o črevný mikrobióm kožných ochorení, predmetom záujmu je aj jeho úloha v patogenéze HS. Podľa literárnych údajov črevná dysbióza podporuje produkciu prozápalových cytokínov a následne tvorbu HS lézií. Syndróm prerastania baktérií v tenkom čreve (SIBO – small intestinal bacterial overgrowth) je stav, ktorý sa vyznačuje zvýšenou koncentráciou baktérií hrubého čreva v tenkom čreve. Eredikácia SIBO bola napr. schopná zlepšiť kožné prejavy pri psoriáze, v zmysle zníženia indexu jej závažnosti. V tomto kontexte existuje hypotéza, že eredikácia SIBO môže mať priaznivý vplyv na závažnosť prejavov zápalových imunitne mediovaných kožných ochorení, vrátane HS.
Hidradenitis suppurativa (HS) is a chronic immune-mediated inflammatory skin disease. It is characterized by an inflammation that affects apocrine gland bearing skin in axillae, groin and under the breasts with the formation of painful nodules, abscesses and purulent discharge, sinuses and scaring. Patients with HS have an increased incidence of inflammatory bowel disease (IBD), which also indicates their cross-sections in the pathogenesis of dysregulation congenital and adaptive immunity. Recently, there has been a significant increase of interest in the intestinal microbiome and skin disease, as much as its role in the pathogenesis of HS. According to literature, intestinal dysbiosis promotes the production of proinflammatory cytokines and consequently the formation of HS lesions. Overgrowth of bacteria in the small intestine (SIBO) is a condition characterized by an increased concentration of bacteria in the large intestine. Eradication of SIBO was able to improve psoriasis measured by the psoriasis severity index. In this context, it is hypothesized that eredication of SIBO may have a beneficial effect on the severity of manifestations in inflammatory immune-mediated skin diseases, including HS.
