Low-grade endotoxemia is associated with cardiovascular events in community-acquired pneumonia.

OBJECTIVES: Community-acquired pneumonia (CAP) is associated with low-grade endotoxemia but its relationship with cardiovascular events (CVE) has not been investigated. METHODS: We evaluated the incidence of CVE including myocardial infarction, stroke, and cardiovascular death in 523 adult patients hospitalized for CAP. Serum lipopolysaccharide (LPS) and zonulin, a marker of gut permeability, were analyzed in the cohort, that was followed-up during hospitalization and up to 43 months thereafter. RESULTS: During the hospital-stay, 55 patients experienced CVE with a progressive increase from the lowest (0.6%) to highest LPS tertile (23.6%, p < 0.001). Logistic regression analyses showed that higher LPS tertile was independently associated with CVE; LPS significantly correlated with age, hs-CRP and zonulin. In a sub-group of 23 CAP patients, blood E. coli DNA was higher in patients compared to 24 controls and correlated with LPS. During the long-term follow-up, 102 new CVE were registered; the highest tertile of LPS levels was associated with incident CVE; Cox regression analysis showed that LPS tertiles, age, history of CHD, and diabetes independently predicted CVE. CONCLUSIONS: In CAP low-grade endotoxemia is associated to short- and long-term risk of CVE. Further study is necessary to assess if lowering LPS by non-absorbable antibiotics may result in improved outcomes.

Endotoxemia is associated with an adverse metabolic profile.

Our aim was to analyze whether endotoxemia, i.e. translocation of LPS to circulation, is reflected in the serum metabolic profile in a general population and in participants with cardiometabolic disorders. We investigated three Finnish cohorts separately and in a meta-analysis (n = 7178), namely population-based FINRISK97, FinnTwin16 consisting of young adult twins, and Parogene, a random cohort of cardiac patients. Endotoxemia was determined as serum LPS activity and metabolome by an NMR platform. Potential effects of body mass index (BMI), smoking, metabolic syndrome (MetS), and coronary heart disease (CHD) status were considered. Endotoxemia was directly associated with concentrations of VLDL, IDL, LDL, and small HDL lipoproteins, VLDL particle diameter, total fatty acids (FA), glycoprotein acetyls (GlycA), aromatic and branched-chain amino acids, and Glc, and inversely associated with concentration of large HDL, diameters of LDL and HDL, as well as unsaturation degree of FAs. Some of these disadvantageous associations were significantly stronger in smokers and subjects with high BMI, but did not differ between participants with different CHD status. In participants with MetS, however, the associations of endotoxemia with FA parameters and GlycA were particularly strong. The metabolic profile in endotoxemia appears highly adverse, involving several inflammatory characters and risk factors for cardiometabolic disorders.

Improvement of Lipoprotein Profile and Metabolic Endotoxemia by a Lifestyle Intervention That Modifies the Gut Microbiota in Subjects With Metabolic Syndrome.

Background Metabolic syndrome (MetS) is a serious health problem over the world; thus, the aim of the present work was to develop a lifestyle intervention to decrease the dysbiosis of gut microbiota and reduce the biochemical abnormalities of MetS. Methods and Results The prevalence of MetS was evaluated in 1065 subjects of Mexico City, Mexico, and the gut microbiota in a subsample. Subjects with MetS were selected for a pragmatic study based on a lifestyle intervention with a low-saturated-fat diet, reduced-energy intake, with functional foods and physical activity, and a second group was selected for a randomized control-placebo study to assess the gut microbiota after the dietary intervention. Prevalence of MetS was 53%, and the higher the body mass index, the higher the gut microbiota dysbiosis. The higher the Homeostatic Model Assessment for Insulin Resistance, the lower the high-density lipoprotein cholesterol concentration. The pragmatic study revealed that after 15 days on a low-saturated-fat diet, there was a 24% reduction in serum triglycerides; and after a 75-day lifestyle intervention, MetS was reduced by 44.8%, with a reduction in low-density lipoprotein cholesterol, small low-density lipoprotein particles, glucose intolerance, lipopolysaccharide, and branched-chain amino acid. The randomized control-placebo study showed that after the lifestyle intervention, there was a decrease in the dysbiosis of the gut microbiota associated with a reduction in the Prevotella/ Bacteroides ratio and an increase in the abundance of Akkermansia muciniphila and Faecalibacterium prausnitzii. Conclusions A lifestyle intervention significantly decreased MetS components, small low-density lipoprotein particle concentration, gut microbiota dysbiosis, and metabolic endotoxemia, reducing the risk of atherosclerosis. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT03611140.

Alkaline Phosphatase Activity and Endotoxemia After Infant Cardiothoracic Surgery.

OBJECTIVE: Infant cardiopulmonary bypass (CPB) increases intestinal permeability leading to endotoxemia. Alkaline phosphatase (AP) reduces endotoxin toxicity in vitro but its effects on endotoxemia in human disease are poorly understood. We assessed the association between serum AP activity and endotoxemia in infants undergoing CPB and determined the effect of ex vivo addition of AP on endotoxemia. METHODS: Prospective cohort study of 62 infants ≤120 days of age undergoing CPB. AP activity and Endotoxin Activity Assay (EAA) were measured pre-operatively, during rewarming, and 24 h after cardiac intensive care unit admission. In 22 subjects, EAA was measured in pre-operative and rewarming whole blood samples with/without addition of 1,600 U/L of human liver AP. RESULTS: AP activity decreased during CPB (mean decrease 94.8U/L; P < 0.0001). Median EAA was 0.41 pre-operation, rose to 0.52 (P < 0.05) during rewarming, and remained stably elevated at 24 h. Subjects with low pre-operative AP activity had significantly higher pre-operative (0.47 vs. 0.36; P < 0.05) and rewarming (0.59 vs. 0.43; P < 0.01) EAA with a trend toward higher EAA at 24 h (0.52 vs. 0.45; P = 0.12). Subjects with low rewarming AP activity showed similar differences that did not reach statistical significance. Ex vivo addition of human liver AP decreased pre-operative EAA by 29% (P < 0.001) and rewarming EAA by 51% (P < 0.0001). CONCLUSION: Endotoxemia is common in infants undergoing CPB. Native AP activity and endotoxemia are inversely related and ex vivo addition of exogenous AP reduces whole blood EAA. Future research should evaluate AP as a therapy to reduce the harmful effects of endotoxemia following infant CPB.

Obesity and Metabolic Syndrome in Kidney Transplantation: The Role of Dietary Fructose and Systemic Endotoxemia.

BACKGROUND: The concepts that obesity is merely a consequence of overeating, and that metabolic health then reflects obesity, may be insufficient and potentially flawed. The role of fructose intake and metabolic endotoxemia has gained attention recently, but data in kidney transplantation are lacking. This study evaluated the risk factors for metabolic syndrome (MS), its components, and other associated markers in kidney transplant recipients (KTRs), focusing particularly on fructose intake and systemic endotoxemia. METHODS: This cross-sectional observational study enrolled 128 KTRs longer than 1 year posttransplantation. Clinical, biochemical, anthropometric, and questionnaire assessments were undertaken. RESULTS: Obesity (body mass index, ≥30 kg/m) and MS (International Diabetes Federation Definition) were found in 36.7% and 50% of KTRs, respectively. Both increased fructose intake (P = 0.01) and endotoxin level (P = 0.02) were independently associated with MS; and higher fructose intake was independently associated with obesity (P < 0.001). Specifically, increased fructose intake was associated with the central obesity (P = 0.01) and hyperglycemia (P < 0.001) criteria of MS, whereas higher endotoxin level was associated with the hypertriglyceridemia (P = 0.003) and low HDL cholesterol concentration (P = 0.002) criteria of MS. Neither saturated fat nor total caloric intakes were independently associated with obesity and MS; and neither obesity nor central obesity were independently associated with the dyslipidemia and hyperglycemia criteria of MS. Principal component analysis demonstrated relationships between higher levels of endotoxin, soluble endothelial selectin, triglycerides, and insulin resistance (r > 0.6), as well as relationships between increased fructose intake, inflammation, and blood glucose (r > 0.6). CONCLUSIONS: Dietary modifications through decreasing fructose intake and addressing systemic endotoxemia are plausible targets for improving metabolic health of KTRs.

Systemic Endotoxin in Peritoneal Dialysis Patients.

Previous reports linked systemic endotoxemia in dialysis patients to increased markers of inflammation, cardiovascular disease, and mortality. Many peritoneal dialysis (PD) patients use acidic, hypertonic dialysates, which could potentially increase gut permeability, resulting in systemic endotoxemia. However, the results from studies measuring endotoxin in PD patients are discordant. We therefore measured systemic endotoxin in 55 PD outpatients attending for routine assessment of peritoneal membrane function; mean age 58.7 ± 16.4 years, 32 (58.2%) male, 21 (38.2%) diabetic, median duration of PD treatment 19.5 (13 - 31) months, 32 (58.2%) using 22.7 g/L dextrose dialysates, and 47 (85.5%) icodextrin. The median systemic endotoxin concentration was 0.0485 (0.0043 - 0.103) Eu/mL. We found no association between endotoxin levels and patient demographics, markers of inflammation, serum albumin, N-terminal pro-brain natriuretic peptide, extracellular volume measured by bioimpedance, blood pressure, PD prescriptions or peritoneal membrane transporter status, or medications. The measurement of endotoxin can be lowered by failure to effectively release protein-bound endotoxin prior to analysis and increased by contamination when taking blood samples and processing and storing the samples. Additionally, contamination with ß-glucan from fungal cell walls and the use of different assays to analyze endotoxin can also give differing results. These factors may help to explain the disparate results reported in different studies. Our study would suggest that exposure to standard peritoneal dialysates does not substantially increase systemic endotoxin. However, until endotoxin assays can measure free and bound endotoxin separately, the role of endotoxin causing inflammation in PD patients remains to be determined.

Endotoxinemia contributes to steatosis, insulin resistance and atherosclerosis in chronic hepatitis C: the role of pro-inflammatory cytokines and oxidative stress.

PURPOSE: Endotoxin is a component of the outer membrane of gram-negative bacteria that live in the intestine. Endotoxinemia is reported in non-alcoholic fatty liver disease and in cirrhotic patients, causing various biological and clinical effects in the host. It is not known whether endotoxinemia occurs in chronic hepatitis C patients (CHC), therefore we evaluated the occurrence of endotoxinemia and its effect on inflammation, liver damage, insulin resistance (IR) and atherosclerosis. METHODS: Consecutive CHC patients assessed by liver biopsy were enrolled. Endotoxinemia was evaluated by LAL test. IR was estimated by HOMA-IR. Serum TNF-α, IL-8, adiponectin and MCP-1 were measured with ELISA tests. Oxidative stress was estimated by circulating IgG against malondialdehyde adducts with human serum albumin (MDA-HAS). Carotid atherosclerosis was assessed by ultrasonography. RESULTS: Endotoxinemia was found in 60% of the 126 patients enrolled. A serum level-dependent association between endotoxinemia, steatosis (p < 0.001) and HOMA-IR (p < 0.006) was observed. Patients with endotoxinemia showed significant increase in TNF-α and IL8 levels. TNF-α correlated with steatosis (p <  0.001) and HOMA-IR (p < 0.03), whereas IL8 correlated with steatosis (p =  <0.001), TNF-α (p < 0.04) and atherosclerosis (p < 0.01). The highest levels of endotoxinemia were associated with oxidative stress and a higher prevalence of carotid atherosclerosis. Multivariate logistic regression analysis showed that the independent factors associated with endotoxinemia were hepatic steatosis, HOMA-IR, IL8 and MDA-HAS. CONCLUSIONS: Endotoxinemia occurs with high frequency in CHC patients and contributes to the development of hepatic steatosis, IR and atherosclerosis through increased pro-inflammatory cytokines and oxidative stress. Anti-endotoxin treatment could be of clinical relevance.

Endotoxemia is associated with acute coronary syndrome in patients with end stage kidney disease.

BACKGROUND: Cardiovascular disease is the major cause of death in patients with end-staged kidney disease (ESRD). Most ESRD patients have systemic inflammation, and increasing the risk of cardiovascular event. Endotoxin derived from lipopolysaccharide of Gram negative bacteria accounts for 70% of intestinal bacteria, leading to release of proinflammatory cytokines and negative cardiovascular effect. Impaired intestinal barriers have been found in some ESRD patients, and may lead to bacteria translocation from gastrointestinal tract. We aim to investigate the association of endotoxemia in ESRD patients and acute coronary syndrome (ACS). METHODS: We collected serum from adult ESRD patients who presented to emergency department (ED) with ACS (30 patients) or without ACS (30 patients) as control from 11/01/2013 to 10/31/2014 in Chi Mei Medical Center in southern Taiwan. Clinical information and lab data were collected. We measured the endotoxin level of the serum of ESRD patients with or without ACS. We used real-time 16S rDNA PCR to detect possible bacteria in the blood of the patients. RESULTS: The endotoxin level of ESRD patients with ACS (0.49 (±0.12) EU/mL) was significantly higher than that of ESRD patients without ACS (0.1 ± 0.08) (p < 0.01). However, the endotoxin level was not correlated with the troponin-I level (r = -0.12). Although endotoxin level was higher in ESRD patients with ACS, bacteria were not detected in the serum by using the real-time 16S rDNA PCR. CONCLUSION: Endotoxin in ESRD patients with ACS was significantly higher than that without ACS. The result suggested that endotoxemia may have a contributory role to cardiovascular disease in ESRD patients.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth. AIM: To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia. METHODS: The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity. RESULTS: A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 µg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 µg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level. CONCLUSIONS: Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

Prevalence and clinical significance of early high Endotoxin Activity in septic shock: An observational study.

PURPOSE: To measure the prevalence of elevated Endotoxin Activity (EA) in a large cohort of patients with Septic Shock (SS), and to assess its value as an early indicator of Gram-Negative (GN) infection, disease severity, and patient risk. MATERIALS AND METHODS: Adult patients were enrolled in this observational study if an EA determination was obtained within 24-h from SS onset. Demographic, clinical, and microbiological data were collected. In-hospital follow-up was also conducted. RESULTS: A high prevalence of endotoxemia was observed in the 107 subjects included, with 82% of patients showing either intermediate (≥0.4 units), or high (≥0.6) EA. Patients with positive cultures for GNs showed a higher mean EA (0.63±0.18 vs. 0.53±0.22; p<0.05). However, the test showed poor accuracy in the identification of GN bacteria as SS causative agents. Significantly higher lactate concentration (p=0.006), SOFA (p=0.04) and inotropic score (p=0.006) were observed in patients with endotoxemia. However, higher EA levels neither influenced mortality, nor length of stay. CONCLUSIONS: Early after SS onset, patients showed a high prevalence of endotoxemia, particularly those infected with GN bacteria. The EA assay might be a useful marker of disease severity. The complexity of such patients, however, limits EA accuracy in identifying GN sepsis and predicting outcome.

The importance of early detection of endotoxemia.

Endotoxin is considered a key signaling molecule in the pathogenesis of sepsis and septic shock. Anti-endotoxin therapies may result in the improvement of a patient's clinical condition and lower mortality. The pressing clinical challenge is to identify patients for whom endotoxin elimination would be the most beneficial. An endotoxin activity assay (EAA) has been available for detection of endotoxins, allowing selection of patients at high risk of endotoxemia in intensive care units (ICUs). We studied a cohort of 172 consecutive patients who had septic shock on admission to the ICU. Endotoxin activity (EA) was measured with a rapid chemiluminescent EAA, regarded as point-of-care testing. Endotoxemia with a mean EA of 0.59 ± 0.14 EAU was present in 104 patients (60%) and absent in 68 patients (EA = 0.25 ± 0.11 EAU). The risk of endotoxemia increased with the presence of a Gram-negative infection [odds ratio (OR) 3.1, 95% confidence interval (CI) 1.6-5.9; P = 0.001] and bacteremia (OR 3.8, 95% CI 1.6-8.9; P = 0.02) but did not change with a diagnosis of peritonitis (OR 1.03, 95% CI 0.54-1.97; P = 0.90). These findings indicate that anti-endotoxin interventions should be tailored to individual patients based on both clinical conditions and measured endotoxin levels.

Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. AIMS: To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia. METHODS: Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. RESULTS: Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers. CONCLUSIONS: Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.

Endotoxemia as a diagnostic tool for patients with suspected bacteremia caused by gram-negative organisms: a meta-analysis of 4 decades of studies.

The clinical significance of endotoxin detection in blood has been evaluated for a broad range of patient groups in over 40 studies published over 4 decades. The influences of Gram-negative (GN) bacteremia species type and patient inclusion criteria on endotoxemia detection rates in published studies remain unclear. Studies were identified after a literature search and manual reviews of article bibliographies, together with a direct approach to authors of potentially eligible studies for data clarifications. The concordance between GN bacteremia and endotoxemia expressed as the summary diagnostic odds ratios (DORs) was derived for three GN bacteremia categories across eligible studies by using a hierarchical summary receiver operating characteristic (HSROC) method. Forty-two studies met broad inclusion criteria, with between 2 and 173 GN bacteremias in each study. Among all 42 studies, the DORs (95% confidence interval) were 3.2 (1.7 to 6.0) and 5.8 (2.4 to 13.7) in association with GN bacteremias with Escherichia coli and those with Pseudomonas aeruginosa, respectively. Among 12 studies of patients with sepsis, the proportion of endotoxemia positivity (95% confidence interval) among patients with P. aeruginosa bacteremia (69% [57 to 79%]; P=0.004) or with Proteus bacteremia (76% [51 to 91%]; P=0.04) was significantly higher than that among patients without GN bacteremia (49% [33 to 64%]), but this was not so for patients bacteremic with E. coli (57% [40 to 73%]; P=0.55). Among studies of the sepsis patient group, the concordance of endotoxemia with GN bacteremia was surprisingly weak, especially for E. coli GN bacteremia.

Endotoxemia in end-stage kidney disease.

Chronic unexplained inflammation remains a prevalent and clinically significant problem for patients with end-stage kidney disease (ESKD), especially in the dialysis population. The causes of persistent inflammation are likely to be multifactorial, but the underlying mechanisms remain to be elucidated. Endotoxins are reported to play a significant role in the pathogenesis of inflammation in patients with ESKD. However, blood endotoxin measurement with the Limulus amoebocyte lysate (LAL) assay is difficult with current detection systems. The reported degree and prevalence of endotoxemia varies in the literature. There are questions as to whether endotoxemia is truly present; whether the varied findings are due to methodological issues with the LAL assay and whether any endotoxemia that might be present plays a role in chronic inflammation frequently observed in ESKD patients. This review will discuss the challenges of accurate blood endotoxin detection, the potential source of blood endotoxins, and the significance of endotoxemia to patient with ESKD.

Efficacy of early postoperative enteral nutrition in supporting patients after esophagectomy.

AIM: This study aims to investigate and evaluate the efficacy and safety of early enteral nutrition (EN) in maintaining and improving the postoperative nutritional status in patients undergoing esophagectomy. METHODS: A randomized, controlled clinical trial was conducted in 120 adult patients with esophageal cancer and undergoing esophagectomy. Patients were randomly divided into two groups receiving either EN (N.=64) or parenteral nutrition (PN) (N.=56) postoperatively. The nutritional intake was isonitrogenic and isocalorie for both groups. Nutritional status was evaluated preoperatively as well as on postoperative day I and day 8. Daily nitrogen balance was measured and 7-day cumulative nitrogen balance was calculated. The levels of serum markers including d-lactate, diamine oxidase (DAO), and endotoxin were determined on 1st, 4th and 8th postoperative day for analyzing intestinal barrier function. Postoperative infection rate and the incidence of nutrition support-related complications were examined. RESULTS: The concentrations of serum albumin and prealbumin in patients of EN group were significantly higher than those in PN group and the concentrations of blood glucose, γ-GT, AKP, TB, and DB were significantly lower compared to those in the PN group (P<0.05). Both daily nitrogen balance and cumulative nitrogen balance of EN group were better than those of PN group since postoperative day III. The serum levels of d-lactate, DAO, and endotoxin of EN group were significantly lower than those of PN group on postoperative day VIII (P<0.01). The incidence of postoperative infections in blood, lung, and intestinal tract in EN group was lower compared to PN group (P<0.05). No severe complications associated with nutritional support occurred in EN group. The time to flatus passage in EN group was significantly shorter, and the cost of nutritional support was significantly less compared to PN group (P<0.05). CONCLUSION: Postoperative early enteral nutrition was safe and feasible for patients undergoing esophagectomy. Compared to PN, EN more efficiently ameliorated postoperational nutritional status of the patients undergoing esophagectomy, played an important role in restoring intestinal barrier function postoperatively, reduced the incidence of postoperative infection, and decreased the cost of hospital stay.

Endotoxemia unrequired in the pathogenesis of pediatric nonalcoholic steatohepatitis.

BACKGROUND AND AIM: Nonalcoholic steatohepatitis (NASH), the severe form of nonalcoholic fatty liver disease, is a serious liver complication associated with obesity. Several studies suggest that endotoxemia is associated with nonalcoholic fatty liver disease and NASH. We aimed to study the correlation of gut microbiome composition and the incidence of endotoxemia in obese patients and NASH patients in comparison with normal controls. METHODS: The abundance of Gram-negative bacteria in the gut microbiomes of normal controls, obese patients with normal liver, and biopsy-proven NASH patients were assessed using 16S rRNA pyrosequencing data. Serum endotoxin was determined by endpoint limulus amebocyte lysate assay. RESULTS: Higher abundance of Gram-negative bacteria in gut microbiome was observed in obese and NASH patients in comparison with normal controls, but no difference was detected between obese and NASH patients. Serum endotoxin is higher in the NASH group than the normal controls. In addition, the obese and NASH patients had a higher incidence of endotoxemia compared with normal controls. However, Spearman's test found no correlation between the abundance of Gram-negative bacteria and serum endotoxin levels. The majority of the NASH patients and the obese patients had low serum endotoxin level. Among NASH patients, serum endotoxin is not correlated with disease severity. CONCLUSIONS: Our data suggest that the gut microbiome composition does not contribute to the incidence of endotoxemia in NASH, and endotoxemia is not required in the pathogenesis of NASH. Our observations highlight the current concept that multiple factors contribute to the development of NASH.

[The influence of the surgical access on the endotoxemia level].

The systemic inflammatory response, induced by the lipopolysaccharides of the normoflora of the operated patients was studied on the example of the plasma changes in 107 patients. All patients were divided in 4 groups, depending on the level of lipopolysaccharides in plasma. Thus, patients with the complicated course of the acute cholecystitis, demonstrated the increased lipopolysaccharides levels. The last correlates with the surgical access, the duration of the operation and early complications development. The results may be used for the diagnostics and decision making in emergency situations.

Endotoxaemia is common in children with Plasmodium falciparum malaria.

BACKGROUND: Children presenting to hospital with recent or current Plasmodium falciparum malaria are at increased the risk of invasive bacterial disease, largely enteric gram-negative organisms (ENGO), which is associated with increased mortality and recurrent morbidity. Although incompletely understood, the most likely source of EGNO is the bowel. We hypothesised that as a result of impaired gut-barrier function endotoxin (lipopolysaccharide), present in the cell-wall of EGNO and in substantial quantities in the gut, is translocated into the bloodstream, and contributes to the pathophysiology of children with severe malaria. METHODS: We conducted a prospective study in 257 children presenting with malaria to two hospitals in Kenya and Uganda. We analysed the clinical presentation, endotoxin and cytokine concentration. RESULTS: Endotoxaemia (endotoxin activity ≥0.4 EAA Units) was observed in 71 (27.6%) children but its presence was independent of both disease severity and outcome. Endotoxaemia was more frequent in children with severe anaemia but not specifically associated with other complications of malaria. Endotoxaemia was associated with a depressed inflammatory and anti-inflammatory cytokine response. Plasma endotoxin levels in severe malaria negatively correlated with IL6, IL10 and TGFß (Spearman rho: TNFα: r=-0.122, p=0.121; IL6: r=-0.330, p<0.0001; IL10: r=-0.461, p<0.0001; TGFß: r=-0.173, p<0.027). CONCLUSIONS: Endotoxaemia is common in malaria and results in temporary immune paralysis, similar to that observed in patients with sepsis and experimentally-induced endotoxaemia. Intense sequestration of P. falciparum-infected erythrocytes within the endothelial bed of the gut has been observed in pathological studies and may lead to gut-barrier dysfuction. The association of endotoxaemia with the anaemia phenotype implies that it may contribute to the dyserythropoesis accompanying malaria through inflammation. Both of these factors feasibly underpin the susceptibility to EGNO co-infection. Further research is required to investigate this initial finding, with a view to future treatment trials targeting mechanism and appropriate antimicrobial treatment.