Serum Lipopolysaccharide-binding Protein Research Articles

Serum LBP Is Associated with Insulin Resistance in Women with PCOS.

IntroductionLipopolysaccharide-binding protein (LBP) is closely associated with many metabolic disorders. However, no study has been done to explore the relationship between LBP and polycystic ovary syndrome (PCOS). The objective of this study was to investigate whether the serum LBP level is elevated and associated with insulin resistance (IR) in PCOS.Participants and DesignIn this cross-sectional study, 117 PCOS patients and 121 age-matched controls were recruited. Hyperinsulinemic-euglycemic clamp was performed with an expression of M value for insulin sensitivity. Fasting serum samples were collected to detect LBP, lipids, insulin, sex hormones and high sensitive C reactive protein (hs-CRP). Pearson’s correlation and multiple linear regression was used to analyze the associations between M value and LBP level.SettingsThe study was performed in a clinical research center.ResultsCompared with controls, PCOS subjects had a significantly higher LBP concentration (33.03±14.59 vs. 24.35±10.31 μg/ml, p<0.001), and lower M value (8.21±3.06 vs. 12.31±1.72 mg/min/kg, p<0.001). Both in lean and overweight/obese individuals, serum LBP level was higher in PCOS subjects than that in controls. M value was negatively correlated with body mass index (BMI), fasting serum insulin, triglycerides, low-density lipoprotein cholesterol (LDL-c), free testosterone, high sensitive C reactive protein (hs-CRP) and LBP, whereas positively correlated with high-density lipoprotein cholesterol (HDL-c) and sex hormone binding globulin (SHBG). Serum LBP level was associated with M value after adjusting for BMI, fasting serum insulin, SHBG, as well as hs-CRP.ConclusionSerum LBP level significantly is elevated in PCOS, and is independently associated with IR in PCOS.

Putative consequences of exposure to Helicobacter pylori infection in patients with coronary heart disease in terms of humoral immune response and inflammation.

IntroductionPathogens, including Helicobacter pylori (Hp), have been suggested to contribute to the development of coronary heart disease (CHD), although the evidence still remains insufficient. The study was focused on the exposure of CHD patients to Hp and resulting anti-Hp heat shock protein B HspB antibody production in relation to the level of serum lipopolysaccharide binding protein (LBP) as a marker of inflammation.Material and methodsOne hundred seventy CHD patients and 58 non-CHD individuals participated in this study. Coronary angiography confirmed the atheromatic background of CHD. The panel of classical risk factors included: arterial hypertension, diabetes, total cholesterol, low-density lipoprotein (LDL)/high-density lipoprotein (HDL) cholesterol, triglycerides, obesity and nicotinism. The Hp status was estimated by 13C urea breath test and serology. Immunoblot and ELISA were used for screening the sera samples for anti-Hp HspB immunoglobulins (Igs) and LBP.ResultsCoronary heart disease patients were exposed to Hp more frequently than non-CHD individuals. This was associated with increased levels of specific anti-Hp IgG2 and IgA as well as total IgA. Hp infected CHD and non-CHD donors produced anti-Hp HspB IgG cross-reacting with human Hsp 60. In CHD patients the LBP level was significantly higher in comparison to non-CHD donors. This was related to the severity of the disease. Type I Hp strains stimulated higher LBP levels than less pathogenic type II isolates.ConclusionsLipopolysaccharide binding protein secreted in excess together with anti-Hp HspB, cross-reacting with human Hsp60, may increase the risk of vascular pathologies in Hp-exposed CHD patients.

Association of Lipopolysaccharide-Binding Protein With Aging-Related Adiposity Change and Prediabetes Among African Ancestry Men.

Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ~6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02-2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.

Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in PD

Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in PD

Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease

BackgroundThe intestine is one of the first affected organs in Parkinson’s disease (PD). PD subjects show abnormal staining for Escherichia coli and α-synuclein in the colon.MethodsWe recruited 52 PD patients and 36 healthy cohabitants. We measured serum markers and quantified the numbers of 19 fecal bacterial groups/genera/species by quantitative RT-PCR of 16S or 23S rRNA. Although the six most predominant bacterial groups/genera/species covered on average 71.3% of total intestinal bacteria, our analysis was not comprehensive compared to metagenome analysis or 16S rRNA amplicon sequencing.ResultsIn PD, the number of Lactobacillus was higher, while the sum of analyzed bacteria, Clostridium coccoides group, and Bacteroides fragilis group were lower than controls. Additionally, the sum of putative hydrogen-producing bacteria was lower in PD. A linear regression model to predict disease durations demonstrated that C. coccoides group and Lactobacillus gasseri subgroup had the largest negative and positive coefficients, respectively. As a linear regression model to predict stool frequencies showed that these bacteria were not associated with constipation, changes in these bacteria were unlikely to represent worsening of constipation in the course of progression of PD. In PD, the serum lipopolysaccharide (LPS)-binding protein levels were lower than controls, while the levels of serum diamine oxidase, a marker for intestinal mucosal integrity, remained unchanged in PD.ConclusionsThe permeability to LPS is likely to be increased without compromising the integrity of intestinal mucosa in PD. The increased intestinal permeability in PD may make the patients susceptible to intestinal dysbiosis. Conversely, intestinal dysbiosis may lead to the increased intestinal permeability. One or both of the two mechanisms may be operational in development and progression of PD.

Acute phase proteins as local biomarkers of respiratory infection in calves.

BackgroundCumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci.ResultsIntra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response.Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection.ConclusionIn conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.

Comparison of ALT Levels and BMI in Patients with Chronic Hepatitis B and Non Alcoholic Steatohepatitis

(NAFLD) is a common chronic liver disease that occurs due to accumulation of fat in liver. The disease is commonly associated with obesity, but prevalence of NAFLD is increasing in non-obese Indian population nowadays. It is postulated that insulin resistance, small bowel bacterial overgrowth, increased intestinal permeability and low-grade endotoxemia may be responsible for steatosis and pathogenesis of NAFLD. The present study was undertaken to evaluate SIBO, endotoxemia and insulin resistance in lean and obese NAFLD patients. Methodology: The prevalence of SIBO was determined using the glucose hydrogen breath test (GHBT). The SIBO was diagnosed positive if the fasting breath hydrogen (H2) concentration was >20 ppm or there was increase of H2 levels >12 ppm over the baseline following ingestion of glucose. The lipopolysaccharide (LPS)-binding protein (LBP) was determined by ELISA. HOMA-IR that measures insulin resistance was assessed by taking fasting serum insulin and fasting blood glucose into consideration. Results: The prevalence of SIBO was determined by GHBT done in171 consecutive NAFLD patients and percentage prevalence was 20.5%. The NAFLD patients were further stratified to groups BMI 25 and percentage prevalence was 4% ( 25 BMI, n = 29), respectively and 0% in disease control (CHB, n = 25) and healthy control (n = 16) group, respectively. The LBP is synthesized by hepatocytes and intestinal epithelial cells. Normal LBP serum concentrations are 5–10 mg/ml and may rise up to 200 mg/ml immediately during induction of an acute-phase response. We have observed LBP level within normal range and among the groups, the mean concentrations in the serum are as follows: 7.91 0.73 mg/ml ( 25 BMI, n = 8), 4.0 1.88 mg/ml (CHB, n = 6), 2.96 1.24 mg/ml (healthy, n = 5). As per IDF guidelines for metabolic syndrome, increased risks of insulin resistance (HOMA IR >1.6–2.5) are 32% ( 25 BMI, n = 29), 13% (CHB, n = 25) and 0% (Healthy, n = 16). The insulin resistant (HOMA IR >2.5) prevalence among groups are 24% ( 25 BMI, n = 29), 9% (CHB, n = 25) and 0% (Healthy, n = 16). Conclusion: We have observed higher prevalence of SIBO in >25 BMI NAFLD group than that of the <25 BMI group. There is also prevalence (3.5%) of methanogenic bacteria in NAFLD population. The LBPmay be considered as surrogate marker for SIBO in GHBT negative cases. Increased risk of insulin resistance was also observed in lean NAFLD patients when compared to obese NAFLD patients. Corresponding author: Baibaswata Nayak. E-mail: baibaswata@yahoo.com

Lipopolysaccharide‐binding protein cannot independently predict type 2 diabetes mellitus: A nested case‐control study

Cross-sectional studies have reported a close association between serum lipopolysaccharide-binding protein (LBP) and many metabolic disorders. However, no longitudinal study has explored the relationship between LBP and type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association between serum LBP levels and the risk of developing T2DM. A 5-year nested case-control study of 3510 individuals was performed as part of the Environment, Inflammation and Metabolic Diseases Study (EIMDS). Clinical data were collected at baseline. Serum levels of LBP and other biochemical factors, such as insulin and high-sensitivity C-reactive protein, were detected 5 years later. Subjects were diagnosed as having T2DM on the basis of results of an oral glucose tolerance test (OGTT) and 1998 World Health Organization criteria. Controls were randomly selected to match cases according to age, gender, and body mass index (BMI) in a 1:1 ratio. Odds ratios (OR) for T2DM were calculated using conditional logistic regression analysis. Over a 5-year follow-up period, 255 subjects developed T2DM. There was no significant difference in serum LBP levels between the T2DM and control groups at baseline (19.78 ± 6.40 versus 20.53 ± 6.99 μg/mL; P = 0.207). Subjects were divided into three groups based on tertiles of LBP concentrations (n = 170 in each group; T1 = 1.31-17.16 μg/mL LBP; T2 = 17.21-22.37 μg/mL LBP; T3 = 22.49-40.08 μg/mL LBP). There was no significant association between the risk of developing T2DM and any of the LBP tertiles in either a simple model or after adjusting for general status and biochemical factors. After matching for gender, age, and BMI, LBP does not improve prediction of the development of T2DM independently.

Markers of systemic exposures to products of intestinal bacteria in a dietary intervention study.

Systemic exposures to intestinal bacteria may play a role in the etiology of the chronic, low-grade inflammation that is associated with western diets. Production of lipopolysaccharide-binding protein (LBP) is one biomarker of increased exposures to intestinal bacteria. This study evaluated whether changes in diet quality could affect serum LBP. This was a randomized, controlled trial of Mediterranean and Healthy Eating diets over 6 months in 120 healthy subjects at increased risk of colon cancer. Blood samples obtained before and after intervention were analyzed for LBP, branched-chain fatty acids characteristic of intestinal bacteria, micronutrients and cytokines. Data were analyzed for changes in LBP over time and for predictors of LBP. Serum concentrations of branched-chain bacterial fatty acids declined significantly in both diet groups. However, there was no significant change in mean serum LBP concentrations with either diet intervention. In serum, LBP was positively associated with CRP and negatively associated with carotenoids both before and after intervention. After intervention, LBP was predicted positively by both CRP and bacterial fatty acid concentrations in serum, and negatively by serum carotenoids and the ω3/ω6 fatty acid ratio. This model accounted for 30 % of the inter-individual variation in serum LBP after intervention. These results indicate that dietary intervention over 6 months was insufficient to alter serum LBP. The relationships with inflammation-related markers, however, indicate that anti-inflammatory strategies other than changes in diet quality, such as weight loss or improved fitness, may have more potential for reducing systemic markers of LPS exposures in well-nourished populations.

Value of Different Diagnostic Markers in Spontaneous Bacterial Peritonitis in HCV Egyptian Cirrhotic Patients

Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening infection occurring in 8% - 30% of ascitic cirrhotic patients; different laboratory diagnostics play a pivotal role for rapid and effective management of SBP patients. Polymorphonuclear leucocytic (PMNLs) count in Ascitic fluid (AF) is the mainstay for the diagnosis, whereas the diagnostic role of alternative biomarkers is rather controversial. In many studies, serum lipopolysaccharide binding protein (LBP) was elevated and Complement 3 (C3) level was significantly consumed in AF of SBP patients. Objectives: To evaluate the diagnostic value of serum LBP and AF C3 in HCV-cirrhotics with SBP in relation to other well-established serum and AF markers. Patients and Methods: One hundred and twenty patients with HCV-cirrhosis and ascites were enrolled and consented: 50 patients with non-SBP ascites in group A and 70 ascitic patients diagnosed with SBP according to clinical suspicion and PMLs count in AF ≥ 250 cells/mm3 in group B in addition to 15 healthy individuals considered as a control group. Serum LBP, CBC, kidney and liver function tests, CRP, fasting and 2 h PP blood glucose and HCV antibodies were measured. AF samples were sent for C3 level, culture, PMNLs count, LDH, CRP, total proteins and albumin. Results: In patients with SBP, the level of serum LBP was not significantly high (p > 0.05) with best cut off value at 0.4500 and poor AUC (<0.6) with low sensitivity and specificity (53.3% & 57.7%, respectively). AF C3 was significantly reduced in AF (p < 0.001) with best cut off value at 144.2 and almost excellent AUC (0.889) with good sensitivity and specificity (82% & 84%, respectively). AF culture showed significant difference between both patients groups (p < 0.05) but with low sensitivity (33.3%). Serum and AF CRP and AF PMNLs count were of high significance in SBP diagnosis (p < 0.001). Conclusion: Serum LBP level showed low significance while AF C3 was significantly reduced in patients with SBP. AF culture showed significant difference between both groups but with low sensitivity while serum, AF levels of CRP and AF PMNLs count were highly significant, and the latter is still considered the gold standard for SBP diagnosis.

A 12 week longitudinal study of microbial translocation and systemic inflammation in undernourished HIV-infected Zambians initiating antiretroviral therapy.

BackgroundUndernourished, HIV-infected adults in sub-Saharan Africa have high levels of systemic inflammation, which is a risk factor for mortality and other adverse health outcomes. We hypothesized that microbial translocation, due to the deleterious effects of HIV and poor nutrition on intestinal defenses and mucosal integrity, contributes to heightened systemic inflammation in this population, and reductions in inflammation on antiretroviral therapy (ART) accompany reductions in translocation.MethodsHIV-infected, Zambian adults with a body mass index <18.5 kg/m2 were recruited for a pilot study to assess the relationships between microbial translocation and systemic inflammation over the first 12 weeks of ART. To assess microbial translocation we measured serum lipopolysaccharide binding protein (LBP), endotoxin core IgG and IgM, and soluble CD14, and to assess intestinal permeability we measured the urinary excretion of an oral lactulose dose normalized to urinary creatinine (Lac/Cr ratio). Linear mixed models were used to assess within-patient changes in these markers relative to serum C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 over 12 weeks, in addition to relationships between variables independent of time point and adjusted for age, sex, and CD4+ count.ResultsThirty-three participants had data from recruitment and at 12 weeks: 55% were male, median age was 36 years, and median baseline CD4+ count was 224 cells/μl. Over the first 12 weeks of ART, there were significant decreases in serum levels of LBP (median change -8.7 μg/ml, p = 0.01), TNF-α receptor 1 (-0.31 ng/ml, p < 0.01), and CRP (-3.5 mg/l, p = 0.02). The change in soluble CD14 level over 12 weeks was positively associated with the change in CRP (p < 0.01) and soluble CD163 (p < 0.01). Pooling data at baseline and 12 weeks, serum LBP was positively associated with CRP (p = 0.01), while endotoxin core IgM was inversely associated with CRP (p = 0.01) and TNF-α receptor 1 (p = 0.04). The Lac/Cr ratio was not associated with any serum biomarkers.ConclusionsIn undernourished HIV-infected adults in Zambia, biomarkers of increased microbial translocation are associated with high levels of systemic inflammation before and after initiation of ART, suggesting that impaired gut immune defenses contribute to innate immune activation in this population.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-521) contains supplementary material, which is available to authorized users.

The value of lipopolysaccharide binding protein for diagnosis of late-onset neonatal sepsis in very low birth weight infants.

To assess the accuracy of lipopolysaccharide binding protein (LBP) for diagnosing late-onset neonatal sepsis (LONS) in very low birth weight (VLBW) infants. Observational, prospective study. We assessed the diagnostic performance of LBP in 26 suspected LONS episodes among 54 patients. Proven and probable LONS episodes were recorded according to established criteria. Receiver operating characteristic curve analysis was performed to evaluate LBP's ability to predict LONS. LONS was diagnosed in 17 of 26 episodes. LBP levels were significantly higher in confirmed LONS episodes (P<0.001). The area under the curve of LBP was 0.89. A cut-off of 17.5 μg/mL had a sensitivity of 94.1%, a specificity of 77.8%, a positive predictive value of 88.9% and a negative predictive value of 87.5%. Serum LBP measurement may be useful as an additional tool in the evaluation of suspected LONS in VLBW infants.

Lipopolysaccharide-binding protein: a valuable biomarker in the differentiation between periprosthetic joint infection and aseptic loosening?

The pre-operative differentiation between periprosthetic joint infection (PJI) and aseptic loosening after total hip (THA) or knee (TKA) arthroplasty is essential for successful therapy and relies in part on the use of molecular markers. The objective of this study was to assess serum levels of lipopolysaccharide-binding protein (LBP) as a diagnostic tool for PJI and to compare its accuracy with standard tests. One hundred and twenty patients presenting with a painful TKA or TKA with indication for surgical revision were included in this prospective, controlled, clinical trial at a single centre. Pre-operative blood and serum samples were collected and analysed for white blood cell (WBC) count, C-reactive protein (CRP) and LBP. The definite diagnosis of periprosthetic joint infection was determined on the basis of clinical, microbiological and histopathological examination. LBP showed significantly higher values in PJI compared with aseptic loosening (p < 0.001) and control (p < 0.001), with a specificity of 66% and a sensitivity of 71% at a cutoff value of >7 ng/ml. In combination with CRP, the positive predictive value for PJI was at 0.67; negative predictive value with both negative was at 0.77. Patients with PJI have elevated serum levels of LBP when compared with patients with aseptic loosening. The use of LBP in serum appears not to be a more accurate marker than CRP level in serum for detecting PJI. On the basis of these results, we cannot recommend the sole use of LBP for differentiating PJI and aseptic loosening following THA and TKA.

Hepatic toll‐like receptor 4 expression is associated with portal inflammation and fibrosis in patients with NAFLD

Notwithstanding evidences implicating the lipopolysaccharides (LPS)/toll-like receptor-4 (TLR4) axis in the pathogenesis of NAFLD, there are no studies aimed to characterize hepatic TLR4 expression in NAFLD patients. We aimed to analyse hepatic TLR4 expression and to verify its relationship with disease activity/evolution in NAFLD patients. Liver tissue from 74 patients with NAFLD and 12 controls was analysed by immunohistochemistry (IHC) for TLR4, α-smooth muscle actin (α-SMA) and cytokeratin-7. IHC for α-SMA was used to evaluate activation of fibrogenic cells (hepatic stellate cells and portal/septal myofibroblasts), that for cytokeratin-7 to count hepatic progenitor cells and bile ducts/ductules, and that for CD68, in a subgroup of 27 patients, for detecting macrophages. Serum LPS-binding protein (LBP), a sensitive marker of LPS activity, was determined in 36 patients and 32 controls. As confirmed by double-labelling experiments, the highest level of TLR4 expression was observed in hepatic progenitor cells, biliary cells and portal/septal macrophages. TLR4-positive hepatic progenitor cells and bile ducts/ductules correlated with portal/interface inflammation, activity of fibrogenic cells and fibrosis (P<0.001). Also the score of TLR4 positivity of porto-septal inflammatory infiltrate correlated with number of hepatic progenitor cells and bile ducts/ductules, activity of fibrogenic cells and fibrosis (P<0.01). Serum LBP was increased in patients compared to controls (P<0.001), and correlated with portal/interface inflammation, activity of portal/septal myofibroblasts and fibrosis (all P<0.05). TLR4 expression by regenerating and inflammatory cells at the porto-septal and interface level, favoured by increased LPS activity, is associated with activation of fibrogenic cells and the degree of fibrosis.

P507 DIFFERENCES IN MINIMAL HEPATIC ENCEPHALOPATHY BETWEEN ALCOHOLIC COMPENSATED LIVER CIRRHOSIS AND VIRAL COMPENSATED LIVER CIRRHOSIS

Background and Aims: Intestinal bacterial overgrowth (IBO) and bacterial translocation (BT) induce a marked proinflammatory activity in cirrhotic patients. The aim was to determine the correlation of serum lipopolysaccharide-binding protein (LBP) with severity of cirrhosis, presence of IBO, bacterial DNA in ascitic fluid (AF) and value of LBP in prediction of mortality. Methods: 42 cirrhotic patients were included in the prospective study. IBO was determined by hydrogen breath test (GASTROLYZER, Bedfont, UK). Bacterial DNA in AF were measured using polymerase chain reaction. LBP was measured by immunometric assay (ELISA Human LBP, Netherlands). The survival rate was evaluated during next forty-eight weeks. Statistical analyses were performed using SPSS 13.0. Results: LBP level increased with severity of cirrhosis according to Child–Pugh (p =0.001), it was higher in ascitic patients than in patients without ascites (p < 0.001). Patients with IBO showed greater (p = 0.001) LBP concentration than patients without IBO (15.74±12.56 versus 4.21±2.59mg/mL). Mean serum LBP level was higher in patients with BT (30.13±10.16mg/mL) in comparison with patients without BT (13.56±9.30mg/mL) (p = 0.005). Positive correlation was found between heart rate and LBP level and negative correlation between blood pressure and LBP level (p < 0.001). Using Cox-regression analysis LBP was found to be one of the risk factors of increased mortality during 48 weeks follow-up (p =0.009). Conclusions: Serum LBP elevation shows a significant correlation with severity of cirrhosis, ascites, presence of IBO and hemodynamic disorders. High LBP level is a reliable marker of BT and independent predictor of increased long-term mortality in cirrhotic patients.

Independent effects of BMI, CRP and carotenoids, but not diet change, on LPS binding protein concentrations (825.2)

Mediterranean diets are known to have anti‐inflammatory effects as compared with Western diets, but the etiology of this association is not known. One factor that could contribute to the chronic, low‐grade pro‐inflammatory state that is associated with Western diets is exposure to intestinal bacteria. Bacterial lipopolysaccharide exposures elicit an immune response that is mediated by lipopolysaccharide binding protein (LBP). LBP helps concentrate lipopolysaccharide at membrane toll‐like receptors. In this study, blood samples were obtained from 120 subjects at high risk for colon cancer before and after randomization to either a Mediterranean or Healthy Eating diet for 6 months. There was no significant change in serum LBP concentrations in either diet arm. In evaluating influential factors at baseline, there was a significant inverse correlation between LBP and serum carotenoids (r = ‐0.299, p&lt;0.001), and positive correlations with C‐reactive protein (r =0.323, p&lt;0.001) and BMI (r =0.322, p=0.004). These three factors had independent effects and accounted for 14% of the variability in serum LBP concentrations at baseline. Since the study was designed to maintain baseline weight, it was not possible to evaluate the effects of weight change on LBP levels. Both interventions did increase serum carotenoids, but the study was only 6 months long which could limit any diet intervention effects. Further research should be designed to delineate the relative effects of diet quality and body weight on serum LBP concentrations. Research on methods to quantify bacterial exposures more directly is also needed to enable studies of the links between intestinal microflora, systemic pro‐inflammatory states and cancer.Grant Funding Source: Supported by NIH grants RO1 CA120381 and P50 CA130810

Bariatric surgery decreased the serum level of an endotoxin-associated marker: lipopolysaccharide-binding protein

BackgroundRecent studies have shown serum lipopolysaccharide binding protein (LBP) is associated with obesity and related metabolic disorder. Bariatric surgery can significantly reduce weight, but reports about the change of LBP after bariatric surgery are limited. We investigated LBP concentration and its associations with clinical variables. MethodsWe enrolled 178 obese patients receiving different bariatric surgeries and 38 normal weight individuals. Fasting blood samples were collected at baseline in all and 1 year after surgery in obese individuals. The serum LBP concentration was measured. ResultsThe percentage of excess weight loss of mini-gastric bypass, Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band were 72.0±20.0%, 65.5±23.0%, 67.2±18.4%, and 16.1±14.3%, respectively. Serum LBP levels were higher in the obese participants than in the normal weight participants (49.9±15.7 versus 25.2±7.5 μg/mL; P<.001) at baseline and significantly decreased to 35.1±22.6 μg/mL after bariatric surgery (P<.001) in the obese group. In the bariatric participants, after multivariate analyses, preoperative LBP and the change of LBP with surgery were independently associated only with high sensitive C-reactive protein (hs-CRP) (P<.001) and the change of hs-CRP (P = .012), respectively, while none of the postoperative variables was independently associated with LBP. ConclusionLBP is associated with body mass index and hs-CRP. Bariatric surgery significantly decreased the serum level of LBP. The relationship between LBP and hs-CRP disappeared after bariatric surgery. (Surg Obes Relat Dis 2014;0:000–000.) © 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Liver transplantation and inflammation: Is lipopolysaccharide binding protein the link?

BackgroundLipopolysaccharide (LPS) binding protein (LBP) is an acute phase protein, which upregulated in response to surgical interventions. LBP plays an important role in modulating LPS-induced inflammatory response. We investigated the expression of LBP and the translocation of LPS in rat models of hepatic ischemia reperfusion injury and liver transplantation (LTx). We also elucidated the effect of LBP on the inflammatory response. MethodsIn this study, cold ischemia (CI), warm ischemia/reperfusion (WI/R), and LTx models were used to model relevant physiologic situations during LTx. Serum and effluent protein levels as well as hepatic-mRNA and protein levels of LBP were examined. LBP released into the effluent during CI was used in a macrophage-LPS-stimulation assay to investigate the role of LBP in modulating the LPS-induced inflammatory response. Blocking experiments using an LBP-inhibitory peptide were performed to confirm the relevance of LPS/LBP for the induction of the inflammatory response. Impairment of the intestinal barrier and translocation of LPS into the liver was visualized by immunohistochemistry. Induction of tumor necrosis factor-alpha (TNF-α) mRNA expression in the liver was taken as indicator of the inflammatory response. ResultsUpregulation of LBP in serum and/or liver tissue was observed after WI/R, CI and LTx, respectively. The LBP released during CI enhanced the LPS induced inflammatory response in vitro as indicated by an induction of TNF-α. On the other hand, blocking LBP using LBP inhibitory peptide, suppressed the induction of TNF-α in vitro markedly. After LTx, elevated serum LBP levels were associated with post-operative LPS translocation and production of inflammatory cytokines. ConclusionsOur findings suggest that translocation of LPS occurs after LTx and that LBP is mediating the LPS-induced inflammatory response after LTx. Blocking LBP using LBP-inhibitory peptide might represent a novel strategy to reduce the I/R-induced inflammatory response.

Serum lipopolysaccharide-binding protein as a marker of atherosclerosis

BackgroundRecently, serum lipopolysaccharide-binding protein (LBP) has been closely associated with coronary artery disease. Here, we aimed to investigate the possible relationship between serum LBP and markers of atherosclerosis. MethodsSerum LBP and carotid intima media thickness (C-IMT) were measured in 332 subjects (101 men and 231 women) who were recruited from an ongoing multicenter project. ResultsSerum LBP was significantly associated with obesity [BMI, fat mass and waist circumference (r > 0.38, p < 0.0001)], HOMA (r = 0.36, p < 0.0001) and high sensitivity CRP (hsCRP) (r = 0.50, p < 0.0001). Circulating LBP was also positively associated with C-IMT (r = 0.27, p < 0.0001). Circulating LBP (β = 0.16; p = 0.001) contributed independently to C-IMT variance, after controlling for the effects of age, gender, BMI and hsCRP. Of note, circulating LBP was found to be increased in the population with carotid plaque (n = 50; 32.7 ± 12.5 vs 28.7 ± 10.7; p = 0.021). ConclusionThe consistent association between serum LBP and the carotid intima media thickness, a widely used atherosclerosis marker, reveals serum LBP as a putative factor related to atherosclerosis.

Effect of acute and chronic red wine consumption on lipopolysaccharide concentrations

Chronic red wine (RW) consumption has been associated with decreased cardiovascular disease risk, mainly attributed to an improvement in lipid profile. RW intake is also able to change the composition of gut microbiota. High fat intake has recently been reported to increase metabolic endotoxemia. The gut microbiota has been proposed as the main resource of plasma lipopolysaccharides (LPSs) in metabolic endotoxemia. We analyzed the effect on LPS concentrations of chronic RW consumption and acute RW intake in relation to high fat intake in middle-aged men. For the chronic study, 10 middle-aged male volunteers were randomly assigned in a crossover trial, and after a washout period, all subjects received RW, dealcoholized red wine (DRW), or gin for 20 d. Serum endotoxin and LPS-binding protein (LBP) concentrations were determined after the washout period and after each of the treatments, and changes in fecal microbiota were quantified. For the acute study, 5 adult men underwent a fat overload or a fat overload together with the consumption of RW, DRW, or gin. Baseline and postprandial serum LPS and LBP concentrations and postprandial chylomicron LPS concentrations were measured. There were no significant differences in the change in LPS or LBP concentrations between chronic RW, DRW, and gin consumption. Bifidobacterium and Prevotella amounts were significantly increased by RW and correlated negatively with LPS concentrations. There were no differences in postprandial serum LPS, LBP, or chylomicron LPS concentrations between acute RW, DRW, or gin intake together with a fatty meal. Chronic RW consumption increases Bifidobacterium and Prevotella amounts, which may have beneficial effects by leading to lower LPS concentrations. This trial was registered at controlled-trials.com as ISRCTN88720134.