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Nutricion Hospitalaria Dec 2018diet plays a decisive role in the prevention and treatment of diseases such as obesity, diabetes, allergies and inflammatory diseases. In addition to this, there are... (Review)
Review
INTRODUCTION
diet plays a decisive role in the prevention and treatment of diseases such as obesity, diabetes, allergies and inflammatory diseases. In addition to this, there are numerous investigations about the role of the microbiota in the genesis of metabolic diseases, especially obesity and its comorbidities.
OBJECTIVE
the aim of this review is to discuss the influence of high-fat diets on dysbiosis and metabolic endotoxemia.
RESULTS AND CONCLUSION
the intestinal microbial ecosystem has been shown to be essential in the performance of functions in the host organism, however, several factors can lead to an imbalance in the homeostasis of the microbiota, known as dysbiosis. High-fat diets are associated with a reduction in intestinal bacterial diversity, changes in membrane integrity, inducing increased permeability and increased lipopolysaccharide (LPS) translocation, changes in the immune system, and generation of low-intensity systemic inflammation. The installed endotoxemia can be considered as a causal factor of subclinical inflammation related to several chronic diseases, and as a result of this, it is essential to know the real impact of hyperlipidic diets on the intestinal microbiota. Thus, it becomes essential to identify dietary strategies that can minimize the inflammatory effects generated from changes in the intestinal microbiota.
Topics: Animals; Diet, High-Fat; Dysbiosis; Endotoxemia; Female; Gastrointestinal Microbiome; Humans; Intestines; MEDLINE; Male; Mice
PubMed: 30525859
DOI: 10.20960/nh.1792 -
Blood Purification 2022Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may... (Observational Study)
Observational Study
INTRODUCTION
Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored.
METHODS
We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review.
RESULTS
Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO2/FiO2 ratio and decreased EAA level after EA therapy.
CONCLUSIONS
We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.
Topics: Acute Kidney Injury; Adsorption; COVID-19; Critical Care; Endotoxemia; Female; Hemoperfusion; Heparin; Humans; Male; Membranes, Artificial; Middle Aged; Polymyxin B; Renal Replacement Therapy; Respiratory Distress Syndrome; Retrospective Studies; SARS-CoV-2; Treatment Outcome
PubMed: 33857940
DOI: 10.1159/000515628 -
Toxins May 2022and are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for... (Review)
Review
and are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for flaccid and spastic paralysis, respectively. The main habitat of these toxigenic bacteria is the environment (soil, sediments, cadavers, decayed plants, intestinal content of healthy carrier animals). can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism. More rarely, colonizes wounds, whereas tetanus is always a result of wound contamination by The synthesis of neurotoxins is strictly regulated by complex regulatory networks. The highest levels of neurotoxins are produced at the end of the exponential growth and in the early stationary growth phase. Both microorganisms, except E, share an alternative sigma factor, BotR and TetR, respectively, the genes of which are located upstream of the neurotoxin genes. These factors are essential for neurotoxin gene expression. and share also a two-component system (TCS) that negatively regulates neurotoxin synthesis, but each microorganism uses additional distinct sets of TCSs. Neurotoxin synthesis is interlocked with the general metabolism, and CodY, a master regulator of metabolism in Gram-positive bacteria, is involved in both clostridial species. The environmental and nutritional factors controlling neurotoxin synthesis are still poorly understood. The transition from amino acid to peptide metabolism seems to be an important factor. Moreover, a small non-coding RNA in , and quorum-sensing systems in and possibly in , also control toxin synthesis. However, both species use also distinct regulatory pathways; this reflects the adaptation of and to different ecological niches.
Topics: Animals; Botulinum Toxins; Botulism; Clostridium botulinum; Clostridium tetani; Humans; Neurotoxins
PubMed: 35737025
DOI: 10.3390/toxins14060364 -
Thrombosis Research Dec 2023Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and... (Review)
Review
Patients with inflammatory bowel disease (IBD) have an increased risk of developing venous thromboembolic events, which have a considerable impact on morbidity and mortality. Chronic inflammation plays a crucial role in the pathogenesis of thrombotic events in patients with IBD. However, many unresolved questions remain, particularly regarding the mechanisms that determine the persistent inflammatory state independent of disease activity. This review explored the role of gut microbiota dysbiosis and intestinal barrier dysfunction, which are considered distinctive features of IBD, in determining pro-thrombotic tendencies. Gut-derived endotoxemia due to the translocation of bacterial lipopolysaccharides (LPS) from the intestine to the bloodstream and the bacterial metabolite trimethylamine-N-oxide (TMAO) are the most important molecules involved in gut dysbiosis-related thrombosis. The pathogenic prothrombotic pathways linked to LPS and TMAO have been discussed. Finally, we present emerging therapeutic approaches that can help reduce LPS-mediated endotoxemia and TMAO, such as restoring intestinal eubiosis, normalizing intestinal barrier function, and counterbalancing the effects of LPS and TMAO.
Topics: Humans; Dysbiosis; Endotoxemia; Lipopolysaccharides; Inflammatory Bowel Diseases; Thrombosis; Gastrointestinal Diseases
PubMed: 37951044
DOI: 10.1016/j.thromres.2023.11.005 -
Journal of Infection in Developing... May 2011Multidrug-resistant typhoid fever (MDRTF) is defined as typhoid fever caused by Salmonella enterica serovar Typhi strains (S. Typhi), which are resistant to the... (Review)
Review
INTRODUCTION
Multidrug-resistant typhoid fever (MDRTF) is defined as typhoid fever caused by Salmonella enterica serovar Typhi strains (S. Typhi), which are resistant to the first-line recommended drugs for treatment such as chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole. Since the mid-1980s, MDRTF has caused outbreaks in several countries in the developing world, resulting in increased morbidity and mortality, especially in affected children below five years of age and those who are malnourished.
METHODOLOGY
Two methods were used to gather the information presented in this article. First PubMed was searched for English language references to published relevant articles. Secondly, chapters on typhoid fever in standard textbooks of paediatric infectious diseases and preventive and social medicine were reviewed.
RESULTS
Although there are no pathognomonic clinical features of MDRTF at the onset of the illness, high fever ( > 104°F), toxaemia, abdominal distension, abdominal tenderness, hepatomegaly and splenomegaly are often reported. The gold standard for the diagnosis of MDRTF is bacterial isolation of the organism in blood cultures. Ciprofloxacin and ceftriaxone are the drugs most commonly used for treatment of MDRTF and produce good clinical results.
CONCLUSION
MDRTF remains a major public health problem, particularly in developing countries. Mass immunization in endemic areas with either the oral live attenuated Typhi 21a or the injectable unconjugated Vi typhoid vaccine, rational use of antibiotics, improvement in public sanitation facilities, availability of clean drinking water, promotion of safe food handling practices and public health education are vital in the prevention of MDRTF.
Topics: Ampicillin; Anti-Bacterial Agents; Chloramphenicol; Communicable Disease Control; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Humans; Salmonella typhi; Trimethoprim, Sulfamethoxazole Drug Combination; Typhoid Fever
PubMed: 21628808
DOI: 10.3855/jidc.1405 -
Biological Research Mar 2023Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as...
BACKGROUND
Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel-mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia.
RESULTS
The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores.
CONCLUSIONS
Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.
Topics: Animals; Rats; Intercellular Adhesion Molecule-1; P-Selectin; TRPM Cation Channels; Endothelial Cells; Endotoxemia; Calcium; Disseminated Intravascular Coagulation; von Willebrand Factor; Sepsis; Endotoxins
PubMed: 36869357
DOI: 10.1186/s40659-023-00419-4 -
Internal and Emergency Medicine Aug 2023Recently, compelling evidence points to dysbiosis and disruption of the epithelial intestinal barrier as major players in the pathophysiology of metabolic disorders,... (Review)
Review
Recently, compelling evidence points to dysbiosis and disruption of the epithelial intestinal barrier as major players in the pathophysiology of metabolic disorders, such as obesity. Upon the intestinal barrier disruption, components from bacterial metabolism and bacteria itself can reach peripheral tissues through circulation. This has been associated with the low-grade inflammation that characterizes obesity and other metabolic diseases. While circulating bacterial DNA has been postulated as a common feature of obesity and even type 2 diabetes, almost no focus has been given to the existence and effects of bacteria in peripheral tissues, namely the adipose tissue. As a symbiont population, it is expected that gut microbiota modulate the immunometabolism of the host, thus influencing energy balance mechanisms and inflammation. Gut inflammatory signals cause direct deleterious inflammatory responses in adipose tissue and may also affect key gut neuroendocrine mechanisms governing nutrient sensing and energy balance, like incretins and ghrelin, which play a role in the gut-brain-adipose tissue axis. Thus, it is of major importance to disclose how gut microbiota and derived signals modulate neuroendocrine and inflammatory pathways, which contribute to the dysfunction of adipose tissue and to the metabolic sequelae of obesity and related disorders. This review summarizes the current knowledge regarding these topics and identifies new perspectives in this field of research, highlighting new pathways toward the reduction of the inflammatory burden of metabolic diseases.
Topics: Humans; Endotoxemia; Diabetes Mellitus, Type 2; Dysbiosis; Inflammation; Metabolic Diseases; Obesity; Adipose Tissue
PubMed: 37014495
DOI: 10.1007/s11739-023-03262-3 -
Frontiers in Cellular and Infection... 2022Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood...
Despite a well-known association between gut barrier defect (leaky gut) and several diseases, data on translocation of pathogen molecules, including bacterial DNA (blood bacteriome), lipopolysaccharide (LPS), and serum (1→3)-β-D-glucan (BG), from the gut to the blood circulation (gut translocation) in dengue are still less studied. Perhaps, dengue infection might induce gut translocation of several pathogenic molecules that affect the disease severity. At the enrollment, there were 31 dengue cases in febrile and critical phases at 4.1 ± 0.3 days and 6.4 ± 1.1 days of illness, respectively, with the leaky gut as indicated by positive lactulose-to-mannitol excretion ratio. With blood bacteriome, the patients with critical phase (more severe dengue; n = 23) demonstrated more predominant abundance in Bacteroidetes and spp. with the lower Bifidobacteria when compared with the healthy control (n = 5). Meanwhile, most of the blood bacteriome results in dengue with febrile stage (n = 8) were comparable to the control, except for the lower Bifidobacteria in dengue cases. Additionally, endotoxemia at the enrollment was demonstrated in five (62.5%) and 19 (82.6%) patients with febrile and critical phases, respectively, while serum BG was detectable in two (25%) and 20 (87%) patients with febrile and critical phases, respectively. There were higher peripheral blood non-classical monocytes and natural killer cells (NK cells) at the enrollment in patients with febrile phage than in the cases with critical stage. Then, non-classical monocytes (CD14CD16) and NK cells (CD56CD16) increased at 4 and 7 days of illness in the cases with critical and febrile stages, respectively, the elevation of LPS and/or BG in serum on day 7 was also associated with the increase in monocytes, NK cells, and cytotoxic T cells. In summary, enhanced Proteobacteria (pathogenic bacteria from blood bacteriomes) along with increased endotoxemia and serum BG (leaky gut syndrome) might be collaborated with the impaired microbial control (lower non-classical monocytes and NK cells) in the critical cases and causing more severe disease of dengue infection.
Topics: Dengue; Dysbiosis; Endotoxemia; Humans; Lipopolysaccharides; Severe Dengue; beta-Glucans
PubMed: 35782108
DOI: 10.3389/fcimb.2022.890817 -
Frontiers in Microbiology 2015Anthrax, caused by Bacillus anthracis, a Gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. There are three types of human... (Review)
Review
Anthrax, caused by Bacillus anthracis, a Gram-positive spore-forming bacterium, is initiated by the entry of spores into the host body. There are three types of human infection: cutaneous, inhalational, and gastrointestinal. For each form, B. anthracis spores need to cross the cutaneous, respiratory or digestive epithelial barriers, respectively, as a first obligate step to establish infection. Anthrax is a toxi-infection: an association of toxemia and rapidly spreading infection progressing to septicemia. The pathogenicity of Bacillus anthracis mainly depends on two toxins and a capsule. The capsule protects bacilli from the immune system, thus promoting systemic dissemination. The toxins alter host cell signaling, thereby paralyzing the immune response of the host and perturbing the endocrine and endothelial systems. In this review, we will mainly focus on the events and mechanisms leading to crossing of the respiratory epithelial barrier, as the majority of studies have addressed inhalational infection. We will discuss the critical gaps of knowledge that need to be addressed to gain a comprehensive view of the initial steps of inhalational anthrax. We will then discuss the few data available on B. anthracis crossing the cutaneous and digestive epithelia.
PubMed: 26500645
DOI: 10.3389/fmicb.2015.01122 -
Nutrition in Clinical Practice :... Apr 2012The human intestinal tract comprises a rich and complex microbial ecosystem. This intestinal microbota provides a large reservoir of potentially toxic molecules,... (Review)
Review
The human intestinal tract comprises a rich and complex microbial ecosystem. This intestinal microbota provides a large reservoir of potentially toxic molecules, including bacterial endotoxin (ie, lipopolysaccharide [LPS]). This potent inflammatory molecule is detectable in the circulation of healthy individuals, and levels transiently increase following ingestion of energy-rich meals. Chronic exposure to circulating endotoxin has been associated with obesity, diabetes, and cardiovascular disease. Western-style meals augment LPS translocation and by this mechanism may contribute to the pathogenesis of these diseases. By contrast, the gut and other organs have evolved mechanisms to detoxify endotoxin and neutralize the potentially inflammatory qualities of circulating endotoxin. Of specific interest to clinicians is evidence that acute postprandial elevation of circulating endotoxin is dependent on meal composition. In this review, the authors present an overview of the biochemical and cellular mechanisms that lead to endotoxemia, with emphasis on the interplay between microbial and nutrition determinants of this condition. The link between endotoxemia, diet, and changes in the intestinal microbiota raise the possibility that dietary interventions can, at least in part, ameliorate the detrimental outcomes of endotoxemia.
Topics: Bacteria; Cardiovascular Diseases; Diabetes Mellitus; Diet; Endotoxemia; Health; Humans; Inflammation; Intestines; Lipopolysaccharides; Metagenome; Obesity
PubMed: 22378797
DOI: 10.1177/0884533611434934