Serum Levels Of Lipopolysaccharide-binding Protein Research Articles

Lipopolysaccharide-binding protein in Crohn's disease patients: a promising noninvasive biomarker monitoring disease activity.

Following STRIDE-II recommendations, the discovery of novel noninvasive biomarkers, beyond the use of C-reactive protein (CRP) and fecal calprotectin, remains a medical need to further improve the monitoring of patients with inflammatory bowel disease (IBD). This study aims to evaluate the potential of serum lipopolysaccharide-binding protein (LBP) in monitoring IBD activity. This retrospective cross-sectional study included 69 IBD patients (43 Crohn's disease and 26 ulcerative colitis) and 82 controls. Serum LBP levels were measured by ELISA. Clinical, biological and endoscopic parameters were analyzed for IBD patients with no reports of missing data. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. IBD patients displayed a significantly higher LBP median [29.6 μg/ml (19.8-38.8) in Crohn's disease and 22.8 (13.7-38.8) in ulcerative colitis] than controls [5.8 (4.7-7.3), P < 0.001] with little overlapping distributions. In Crohn's disease patients, LBP levels gradually increased with endoscopic activity scores demonstrating a 1.7-fold rise in active patients compared to remitter patients ( P = 0.02). LBP level exhibited a positive correlation with CRP ( ρ = 0.75, P < 0.001) as well as fecal calprotectin ( ρ = 0.42, P < 0.01), both of which further increased when excluding cases that did not match endoscopic activity. LBP might be a promising noninvasive biomarker for monitoring disease activity, especially in Crohn's disease patients. In clinical situations where current biomarkers lack sensitivity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.

Bacterial DNA Translocation Is Associated With Overt Hepatic Encephalopathy and Mortality in Patients With Cirrhosis.

Data on the relationship between bacterial translocation, hepatic encephalopathy (HE), and mortality are scarce. This study aimed to assess the association between bacterial DNA (bactDNA) translocation, inflammatory response, ammonia levels, and severity of HE in patients with cirrhosis, as well as the role of bactDNA translocation in predicting mortality. Cirrhotic patients without bacterial infection were prospectively enrolled between June 2022 and January 2023. Grading of HE was classified by the West Haven Criteria and Psychometric Hepatic Encephalopathy Score ≤ -5. Overall, 294 cirrhotic patients were enrolled, with 92 (31.3%) and 58 (19.7%) having covert and overt HE, respectively. BactDNA translocation was detected in 36.1% of patients (n = 106). Patients with overt HE had more bactDNA translocation and higher serum lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, interleukin-6 (IL-6), and ammonia levels than those without HE. Patients with detectable bactDNA had higher white cell counts and serum LBP and IL-6 levels than those without. By contrast, bactDNA, serum LBP, and soluble CD14 levels were comparable between patients with covert HE and those without HE. The multivariate Cox regression analysis revealed that bactDNA translocation (hazard ratio [HR] = 2.49, 95% confidence interval [CI]: 1.22-5.11), Model for End-Stage Liver Disease score (HR = 1.12, 95% CI: 1.09-1.16), age (HR = 1.05, 95% CI: 1.000-1.002), and baseline IL-6 (HR = 1.001, 95% CI: 1.000-1.002) were independent factors associated with 6-month mortality. Apart from hyperammonemia, bactDNA translocation is a possible factor associated with overt HE in cirrhotic patients. BactDNA translocation and IL-6 are independent factors associated with 6-month mortality.

P418 Lipopolysaccharide-Binding Protein (LBP) in Crohn's Disease (CD) Patients: A Promising Non-Invasive Biomarker Monitoring Disease Activity

Abstract Background Current biomarkers of inflammatory bowel disease (IBD) monitoring (serum C-reactive protein (CRP) and faecal calprotectin (FC)) have limitations in terms of specificity (SP) and sensitivity (SE), especially for Crohn’s disease (CD) patients. Lipopolysaccharide-binding protein (LBP) is a soluble acute-phase protein and is thought to partly reflect intestinal permeability by binding to bacterial lipopolysaccharides. The search for new biomarkers to monitor disease activity would improve the management of IBD patients. Methods This is a retrospective study including 69 IBD patients (43 CD and 26 ulcerative colitis (UC)) and 21 healthy controls (HC). Serum LBP levels were measured by enzyme-linked immunosorbent assay. Clinical, biological and endoscopic parameters were analysed for IBD patients. Statistical tests, including nonparametric tests and receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic accuracy of LBP. Results Demographics and baseline data of the overall cohort is presented in Table 1. IBD patients displayed a significantly higher LBP median (29.6 µg/mL [19.8-38.8] in CD and 22.8 [13.7-38.8] in UC) than HC (5.5 [4.4-6.5], P &amp;lt; 0.001) with no overlapping distributions, a finding supported by an AUC of 0.997 and 0.989, respectively for CD and UC patients (Figures 1A). In CD patients, LBP levels gradually increased with endoscopic severity, demonstrating a 1.7-fold rise in active patients compared to remitter patients (P=0.02) (Figure 1B). LBP levels were higher in Montreal B1 compared to B2 and B3 CD patients (P &amp;lt; 0.001) (Figure 1C). Overall, a robust correlation was observed between LBP and CRP (ρ=0.75, P &amp;lt; 0.001). The correlation increased upon the exclusion of cases with normal CRP levels but active endoscopic disease (ρ=0.79, P &amp;lt; 0.001). In those endoscopically active patients with normal CRP, LBP level was higher than in remitter patients (34.3 [29.4-37.6] vs 19.1 [10-24.7], P=0.01) with a discriminative cut-off of 25 µg/mL (SE of 100%, SP of 89%). Likewise, LBP level exhibited a positive correlation with FC (ρ=0.42, P &amp;lt; 0.01) which was further strengthened after excluding cases where FC measurements did not align with endoscopic activity (ρ=0.53, P &amp;lt; 0.01). The median LBP for those patients was 25.6 [18.5-31.5], reflecting again the interest of LBP measurement to evaluate CD activity when FC lacks sensibility. Conclusion Our study suggests that LBP might be a promising non-invasive biomarker for monitoring disease activity, especially in CD patients. Furthermore, in clinical situations where current biomarkers (CRP and FC) lack sensitivity for assessing disease activity, LBP could be discriminative and help filling the gap for reliable therapeutic decisions.

Serum Lipopolysaccharide-binding Protein Levels and the Incidence of Metabolic Syndrome in a General Japanese Population: the Hisayama Study.

The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population. 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1-4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model. At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59-5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07). In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Impact of small intestinal bacterial overgrowth on systemic inflammation, circulatory and renal function, and liver fibrosis in patients with cirrhosis and ascites.

Small intestinal bacterial overgrowth (SIBO) occurs frequently in patients with cirrhosis, particularly in those with ascites, and promotes the translocation of gut-derived bacterial products into the portal and systemic circulation. We investigated the effects of SIBO on systemic inflammatory activity, circulatory and renal function, and the degree of liver fibrosis in patients with cirrhosis and ascites. Eighty patients with cirrhosis and ascites were prospectively enrolled. SIBO was determined by lactulose breath test. Serum levels of lipopolysaccharide-binding protein (LBP), tumor necrosis factor-α, and interleukin-6, mean arterial pressure (MAP), cardiac output (CO) by echocardiography, systemic vascular resistance (SVR) as MAP/CO ratio, plasma renin activity (PRA), plasma aldosterone, radioisotope-assessed glomerular filtration rate (GFR), and liver stiffness by shear wave elastography were evaluated. SIBO was detected in 58 patients (72.5%). Compared to patients without SIBO, those diagnosed with SIBO had significantly higher LBP levels (P<0.001), significantly lower MAP (P<0.001) and SVR (P<0.001), and significantly higher CO (P=0.002) and PRA (P<0.001). Patients with SIBO had significantly lower GFR (P=0.02) and higher liver stiffness (P=0.04) compared to those without SIBO. The presence of SIBO was independently associated with LBP (P=0.007) and PRA (P=0.01). Among patients with SIBO, peak breath hydrogen concentration was significantly correlated with serum LBP (P<0.001), MAP (P<0.001), CO (P=0.008), SVR (P=0.001), PRA (P=0.005), plasma aldosterone (P<0.001), GFR (P<0.001), and liver stiffness (P=0.004). SIBO in patients with cirrhosis and ascites may predispose to greater systemic inflammation, circulatory and renal dysfunction, and more advanced liver fibrosis.

Leaky gut and inflammatory biomarkers in a medication overuse headache model in male rats.

Medication overuse is common among chronic migraine patients and nonsteroidal antiinflammatory drugs (NSAIDs) are the most frequently overused drugs. The pathophysiological mechanisms underlying medication overuse headache (MOH) are not completely understood. Intestinal hyperpermeability and leaky gut are reported in patients using NSAIDs. The aim of the study is to investigate the role of leaky gut and inflammation in an MOH model MOH model in male rats. The study was conducted in male Sprague Dawley rats. There were two experimental groups. The first group was the chronic NSAID group in which the rats received mefenamic acid (n = 8) for four weeks intraperitoneally (ip) and the second group was the vehicle group (n = 8) that received 5% dimethyl sulfoxide+sesame oil (ip) for 4 weeks. We assessed spontaneous pain-like behavior, periorbital mechanical withdrawal thresholds, and anxiety-like behavior using an elevated plus maze test. After behavioral testing, serum levels of occludin and lipopolysaccharide-binding protein (LBP) and brain levels of IL-17, IL-6, and high mobility group box 1 protein (HMGB1) were evaluated with ELISA.Results: Serum LBP and occludin levels and brain IL-17 and HMGB1 levels were significantly elevated in the chronic NSAID group compared to its vehicle (p = 0.006, p = 0.016, p = 0.016 and p = 0.016 respectively) while brain IL-6 levels were comparable (p = 0.67) between the groups. The chronic NSAID group showed pain-like and anxiety-like behavior in behavioral tests. Brain IL-17 level was positively correlated with number of head shakes (r = 0.64, p = 0.045), brain IL-6 level was negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.71, p = 0.049), and serum occludin level was positively correlated with grooming duration (r = 0.73, p = 0.032) in chronic NSAID group. Elevated serum occludin and LBP levels and brain IL-17 and HMGB1 levels indicate a possible role of leaky gut and inflammation in an MOH model in male rats. Additionally, a significant correlation between pain behavior and markers of inflammation and intestinal hyperpermeability, supports the role of inflammation and leaky gut in MOH pathophysiology.

Intestinal permeability is associated with aggravated inflammation and myofibroblast accumulation in Graves' orbitopathy: the MicroGO study.

Graves' disease (GD) and Graves' orbitopathy (GO) result from ongoing stimulation of the TSH receptor due to autoantibodies acting as persistent agonists. Orbital pre-adipocytes and fibroblasts also express the TSH receptor, resulting in expanded retro-orbital tissue and causing exophthalmos and limited eye movement. Recent studies have shown that GD/GO patients have a disturbed gut microbiome composition, which has been associated with increased intestinal permeability. This study hypothesizes that enhanced intestinal permeability may aggravate orbital inflammation and, thus, increase myofibroblast differentiation and the degree of fibrosis. Two distinct cohorts of GO patients were studied, one of which was a unique cohort consisting of blood, fecal, and retro-orbital tissue samples. Intestinal permeability was assessed by measuring serum lipopolysaccharide-binding protein (LBP), zonulin, TLR5, and TLR9 ligands. The influx of macrophages and accumulation of T-cells and myofibroblast were quantified in orbital connective tissue. The NanoString immune-oncology RNA targets panel was used to determine the transcriptional profile of active fibrotic areas within orbital sections. GO patients displayed significantly higher LBP serum concentrations than healthy controls. Within the MicroGO cohort, patients with high serum LBP levels also showed higher levels of zonulin and TLR5 and TLR9 ligands in their circulation. The increased intestinal permeability was accompanied by augmented expression of genes marking immune cell infiltration and encoding key proteins for immune cell adhesion, antigen presentation, and cytokine signaling in the orbital tissue. Macrophage influx was positively linked to the extent of T cell influx and fibroblast activation within GO-affected orbital tissues. Moreover, serum LBP levels significantly correlated with the abundance of specific Gram-negative gut bacteria, linking the gut to local orbital inflammation. These results indicate that GO patients have enhanced intestinal permeability. The subsequent translocation of bacterial compounds to the systemic circulation may aggravate inflammatory processes within the orbital tissue and, as a consequence, augment the proportion of activated myofibroblasts, which actively secrete extracellular matrix leading to retro-orbital tissue expansion. These findings warrant further exploration to assess the correlation between specific inflammatory pathways in the orbital tissue and the gut microbiota composition and may pave the way for new microbiota-targeting therapies.

Medication overuse headache is associated with elevated lipopolysaccharide binding protein and pro-inflammatory molecules in the bloodstream

ObjectiveMedication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used analgesics worldwide and they are known to induce leaky gut. In this study, we aimed to investigate whether NSAID induced MOH is associated with altered circulating lipopolysaccharide binding protein (LBP) levels and inflammatory molecules.Materials and methodsPiroxicam (10 mg/kg/day, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain behavior was evaluated by periorbital withdrawal thresholds, head-face grooming, freezing, and head shake behavior. Serum samples and brain tissues were collected to measure circulating LBP, tight junction protein occludin, adherens junction protein vascular endothelial (VE)-cadherin, calcitonin gene-related peptide (CGRP), IL-6 levels and brain high mobility group box-1 (HMGB1) and IL-17 levels.ResultsChronic piroxicam exposure resulted in decreased periorbital mechanical withdrawal thresholds, increased head-face grooming, freezing, and head shake behavior compared to vehicle administration. Serum LBP, CGRP, IL-6, IL-17, occludin, VE-cadherin levels and brain IL-17 and HMGB1 levels were significantly higher in piroxicam group compared to controls. Serum LBP was positively correlated with occludin (r = 0.611), VE-cadherin (r = 0.588), CGRP (r = 0.706), HMGB1 (r = 0.618) and head shakes (r = 0.921), and negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.740).ConclusionElevated serum LBP, VE-cadherin and occludin levels indicating disrupted intestinal barrier function and leakage of LPS into the systemic circulation were shown in female rats with MOH. LPS induced low-grade inflammation and elevated nociceptive and/or pro-inflammatory molecules such as HMGB1, IL-6, IL-17 and CGRP may play a role in the development and maintenance of MOH. Interference with leaky gut and pro-inflammatory nociceptive molecules could also be a target for sustained management of MOH.

Serum trimethylamine N-oxide and lipopolysaccharide binding protein levels among children diagnosed with autism spectrum disorder.

In the literature, there have been several studies available investigating the relationship between autism spectrum disorder and intestinal permeability. In this study, it is aimed to examine the relationship between the levels of trimethylamine N-oxide (TMAO), which is a parameter associated with intestinal permeability, and lipopolysaccharide binding protein (LBP), which is a marker associated with bacterial translocation from the intestine, in patients with autism spectrum disorder (ASD) and healthy controls. Fifty-three children with ASD as the patient group and 30 healthy children as the control group have been included in the study. The diagnostic evaluation has been made according to DSM-5 criteria. According to the obtained results, there has been no significant difference between groups in terms of serum TMAO and LBP levels. Considering the existence of various studies that found different results on ASD and intestinal permeability, it is thought that the studies conducted in this field that did not find statistically different results will also make a contribution to the literature.

Bacterial translocation markers and toll-like receptors in biliary atresia following successful portoenterostomy.

The gut-liver axis may contribute to pathophysiology of cholestatic liver disorders like biliary atresia (BA) by bacterial translocation (BT). Toll-like receptors (TLR) are pattern recognition receptors known to activate innate immunity and secretion of inflammatory cytokines. Herein, we examined BT-associated biomarkers and TLRs in relation to liver injury after successful portoenterostomy (SPE) in BA. Serum levels of lipopolysaccharide-binding protein (LBP), CD14, LAL, TNF-α, IL-6 and FABP2 along with liver expression of TLRs (TLR1, TLR4, TLR7 and TLR9), LBP and CD14 were measured during median 4.9 (1.7-10.6) years follow-up after SPE in 45 BA patients. Serum LBP, CD14, TNF-α and IL-6 all increased after SPE whereas LAL and FABP-2 remained unchanged. Serum LBP correlated positively with CD14 and markers of hepatocyte injury and cholestasis, but not with Metavir fibrosis stage, transcriptional markers for fibrosis (ACTA2) or ductular reaction. Serum CD14 concentration was significantly higher in patients with portal hypertension than without. While liver expression of TLR4 and LBP remained low, TLR7 and TLR1 showed marked BA-specific increases, and TLR7 correlated with Metavir fibrosis stage and ACTA2. BT does not seem to play a significant role in liver injury after SPE in our series of BA patients.

Intestinal microbiome characterization of adult Brazilian men with psoriasis compared to omnivore and vegetarian controls

BackgroundPsoriasis is a chronic inflammatory disease associated with systemic inflammation and comorbidities. Changes in the composition of the intestinal microbiome are involved in the pathogenesis of inflammatory diseases and metabolic syndrome. Characterizing the intestinal microbiome of patients with psoriasis may be relevant for the understanding of its clinical course and comorbidity prevention. ObjectiveTo characterize the intestinal microbiome of men with psoriasis compared to omnivore and vegetarian controls (without psoriasis). MethodCross-sectional study of 42 adult males: 21 omnivores with psoriasis; and controls: 14 omnivores and 7 vegetarian individuals. The characterization of the intestinal microbiome was performed by metagenomic analysis. Serum levels of lipopolysaccharide-binding protein (LPB) and C-reactive protein (CRP) were evaluated. ResultsThe groups differed from each other regarding nutritional aspects and microbiome; individuals with psoriasis had a higher consumption of protein and lower consumption of fibers. Levels of LPB, CRP, and the Firmicutes/Bacteroidetes ratio were higher in the group with psoriasis than in the vegetarian group (p<0.05). The genera Prevotella, Mogibacterium, Dorea, Bifidobacterium and Coprococcus, differed in the group with psoriasis compared to vegetarians; the genera Mogibacterium, Collinsella and Desulfovibrio differed from omnivores. A microbiome pattern linked to psoriasis (plsPSO) was identified, which was associated with higher LPB levels (rho=0.39; p=0.02), and lower dietary fiber intake (rho=−0.71; p<0.01). Study limitationsOnly adult men were evaluated. ConclusionA difference was identified in the intestinal microbiome of adult men with psoriasis when compared to healthy omnivores and vegetarian controls. The identified microbiome pattern was correlated with dietary fiber intake and serum levels of LPB.

Nifuroxazide Has Better Efficacy Than Probiotic Treatment in Adult Patients with Acute Diarrheal Syndrome.

Zonulin is a physiological protein that regulates the tight connections and permeability of the intestine, serving as a biomarker for impaired intestinal permeability. The aim of this study was to examine zonulin levels in preeclampsia, to investigate its associations with the cellular immune response marker soluble interleukin-2 receptor (sIL-2R) and exogenous antigen load marker lipopolysaccharide binding protein (LBP) and to evaluate the implications of these findings in the etiopathogenesis of preeclampsia. We designed a cross-sectional case-control study and enrolled 22 pregnant women with preeclampsia and 22 healthy pregnant controls. Plasma zonulin levels were determined by ELISA. Serum sIL-2R and LBP levels were assessed by chemiluminescent immunometric methods. Women with preeclampsia had lower levels of plasma zonulin and serum LBP than normotensive healthy controls (p<0,05). The difference in serum sIL-2R levels was not significant (p: 0,751). There was a negative correlation between plasma zonulin and serum urea (r: -0.319, p: 0.035) and a positive correlation between serum sIL-2R and ALT (r: 0,335, p: 0,026) and AST (r: 0,319, p: 0,035). We found that zonulin and LBP, but not sIL-2R, levels were significantly lower in pregnant women with preeclampsia as compared with healthy pregnant controls. Reduced intestinal permeability in preeclampsia might be associated with impaired immune system functions or a lower fat mass and malnutrition. Further studies are needed to elucidate the exact pathogenetic role of intestinal permeability in preeclampsia.

The influence of bacterial translocation and systemic inflammation on the nutrition, skeletal muscles, and survival of patients with liver cirrhosis

Annotation. Malnutrition and sarcopenia are common prognosis-modifying complications of liver cirrhosis (LC). Bacterial translocation and systemic inflammation may be involved in the development of nutritional and muscle insufficiency in LC. The aim of the study was to assess the relationship between serum markers of bacterial translocation and systemic inflammation with nutrition, skeletal muscle, and survival in patients with decompensated LC. 74 patients (age 55.3±11.4 years) were included in the study. Nutritional status was assessed using the Patient-Generated Subjective Global Assessment (PG-SGA). Skeletal muscle mass was assessed using the Skeletal Muscle Index (SMI), and muscle strength was assessed by handgrip strength. The level of lipopolysaccharide-binding protein (LBP), interleukin-6 (Interleukin-6, IL-6), and C-reactive protein (C Reactive Protein, CRP) in blood serum was determined by enzyme immunoassay (ELISA). Statistical data processing was performed in SPSS22. It was found that serum LBP, IL-6, and CRP levels moderately correlated with PG-SGA (r= 0.549, 0.434, and 0.453, respectively, p˂0.005), SMI (r= -0.517, -0.518, and -0.468, respectively, p˂0.005), and handgrip strength (r= -0.338, -0.427, and -0.423, respectively, p˂0.005), and predicted severe malnutrition (AUC (LBP) = 0.746; AUC (IL-6) = 0.672; AUC (CRP) = 0.745, p˂0.05) and sarcopenia (AUC (LBP) = 0.861; AUC (IL-6) = 0.789; AUC (CRP) = 0.744, p˂0.01). 42 patients died from LC complications during the follow-up (Me 367 (82-569) days). In the Kaplan-Meier analysis, the mortality of patients with high levels of LBP (more than 33.4 pg/ml), IL-6 (more than 7.68 pg/ml), and CRP (more than 5.52 mg/l) were significantly higher than that of patients with conditionally low levels. Further studies are needed to determine whether correction of bacterial translocation and systemic inflammation can improve nutritional, skeletal muscle status, and survival in patients with decompensated LC.

Serum lipopolysaccharide-binding protein levels and cardiovascular events in hemodialysis patients: A prospective cohort study.

Patients with end-stage kidney disease (ESKD) exhibit an elevated cardiovascular risk. Chronic inflammation is one of the main mechanisms of cardiovascular disease (CVD). Lipopolysaccharide has been proposed as a link between systemic inflammation and CVD. Herein, we evaluated whether lipopolysaccharide-binding protein (LBP), a surrogate marker of lipopolysaccharide and consequent inflammation, is associated with cardiovascular events in ESKD. We performed a prospective cohort study of maintenance haemodialysis patients. Baseline serum LBP levels were categorized into tertiles and also modelled continuously for analyses. Cox regression methods were used to evaluate the association of serum LBP levels with cardiovascular events. A total of 360 haemodialysis patients were included in this analysis. During a median follow-up of 3.1 years, 90 (25.0%) patients had cardiovascular events. Patients in the upper tertile of serum LBP levels had a significantly greater risk of cardiovascular events [hazard ratio (HR) 4.87; 95% confidence intervals (CI), 2.12-11.15] than those in the lower tertile, independent of age, sex, hypertension, diabetes, CVD, dialysis vintage, body mass index, non-high-density lipoprotein cholesterol, albumin, phosphorus, high-sensitivity C-reactive protein, and interleukin-6. The association was consistent regardless of whether competing risk of death was accounted for (subdistribution HR 4.87; 95% CI, 1.96-12.11 for upper versus lower tertiles) or serum LBP was analysed as a continuous variable (HR 1.30; 95% CI, 1.02-1.66 per 1 SD increment). Serum LBP levels were independently associated with cardiovascular events in heomodialysis patients. LBP might serve as a novel biomarker for CVD in ESKD.

The diversity and abundance of gut microbiota are associated with the pain sensation threshold in the Japanese population

Small fibre neuropathy (SFN) is an initial pathology of diabetic polyneuropathy (DPN). Serum lipopolysaccharide binding protein levels are positively correlated with the pain threshold in the foot, suggesting that the abundance of gut Gram-negative bacilli, which are a source of lipopolysaccharides, may be involved in the development of DPN. Furthermore, the abundance of the gut and oral microbiota is assumed to be involved in the pathogenesis of diabetes. Nevertheless, the association between SFN and the microbiota has not been clarified. A total of 1056 individuals were recruited in the 2018 Iwaki Health Promotion Project. Pain sensation was evaluated based on the pain threshold from intraepidermal electrical stimulation (PINT). Patients with PINT scores <0.15 mA were categorized into the low-PINT group (n = 718); otherwise, they were categorized into the high-PINT group (n = 283). Furthermore, each group was divided into the subjects with or without glucose tolerance based on HbA1c levels, fasting blood glucose levels and diabetic history. Principal coordinate analysis and α- and β-diversity of the microbiota were evaluated. The correlation between clinical and microbiota data was examined. Oral microbiota diversity showed no structural differences according to PINT scores, whereas principal coordinate analysis and α- and β-diversity revealed significant structural differences in gut microbiota (p < 0.01, p < 0.05 and p < 0.05, respectively), even after the participants with glucose intolerance were excluded (p < 0.01, p < 0.05 and p < 0.05, respectively). The relative abundance of the genus Bacteroides was significantly lower in high-PINT participants compared with low-PINT participants (10 ± 6.7% vs. 11.3 ± 7.0%, p < 0.01), even after the exclusion of subjects with diabetes and impaired fasting glucose (10.0 ± 6.5% vs. 11.2 ± 6.9%, p < 0.05). In univariate linear regression analyses, PINT was significantly correlated with metabolic syndrome parameters, eGFR, uric acid level and the abundance of Bacteroides. The correlation between Bacteroides and PINT scores remained significant after adjustment for multiple factors (β = −0.07181, p < 0.05). Changes of bacterial diversity and a low abundance of gut Bacteroides were correlated with elevated PINT scores in the Japanese population. This correlation may represent a new therapeutic option for SFN.

Effect of time restricted feeding on anthropometric measures, eating behavior, stress, and brain-derived neurotrophic factor (BDNF) and lipopolysaccharide-binding protein (LBP) levels in women with overweight/obesity and food addiction: a study protocol for a randomized clinical trial

BackgroundFood addiction is one of the behavioral factors that play an important role in the pathogenesis of obesity. Much evidence is available suggesting intestinal microbiomes can play a role in eating behavior, body composition, and BDNF levels, and they can be modified by time-restricted feeding (TRF). So, this study will aim to evaluate the effect of TRF on anthropometric measures, eating behavior, stress, and serum BDNF and LBP levels in women with overweight/obesity and food addiction.MethodsWe will carry out a randomized clinical trial for 8 weeks to evaluate the effect of a TRF on anthropometric measures, eating behavior, stress level, serum BDNF and LBP levels in women with overweight/obesity and food addiction.DiscussionGiven the effect of BDNF on regulating eating behavior and body weight and the effect of dietary restrictions on BDNF and the gut microbiome, the TRF diet could possibly be a new way to successfully manage weight through modifying BDNF in people with eating disorders, including food addiction.Trial registrationIranian Registry of Clinical Trials IRCT20131228015968N7. Registered on 25 October 2020.

Dietary Advanced Glycation End Products Shift the Gut Microbiota Composition and Induce Insulin Resistance in Mice.

ObjectiveThis study aimed to explore the associations between gut microbiota characteristics and glycometabolic profiles in mice fed diets high in advanced glycation end products (AGEs).MethodsC57BL/6 mice were exposed to a heat-treated diet or exogenous AGEs for 24 weeks, and glucose metabolism was assessed via the intraperitoneal glucose-tolerance test (IPGTT). Serum AGE and lipopolysaccharide-binding protein (LBP) levels were quantified using ELISA kits. 16S rDNA sequencing was performed to analyze the changes in gut microbiota according to α- and β-diversity. Key operational taxonomic units (OTUs) were evaluated, and co-abundance groups (CAGs) were delineated using weighted correlation network analysis. Associations between CAGs and clinical parameters were analyzed using Spearman correlation; predictive functional analysis of gut microbiota was performed using Kyoto Encyclopedia of Genes and Genomes data.ResultsWe identified significant increases in fasting blood glucose (FBG) and fasting insulin levels, as well as homeostatic model assessment insulin resistance (HOMA-IR) and glucose area under the receiver operating characteristic curve from IPGTT, in the high-AGE diet groups relative to controls at week 24. Serum AGE and LBP levels were elevated, and the α- and β-diversity of gut microbiota reduced in high-AGE diet groups. We identified 92 key OTUs that clustered into six CAGs, revealing positive correlations between CAG2/3/5 and insulin levels and mice weight and negative correlations between CAG1/3/4/5 and AGE, FBG, and LBP levels and HOMA-IR in mice fed high-AGE diets. We observed a reduced abundance of butyrate-producing bacteria, including Bacteroidales_S24-7, Ruminococcaceae, and Lachnospiraceae, in mice fed high-AGE diets, with pathway analysis of gut microbiota revealing significantly enriched fructose and mannose metabolism.ConclusionHigh-AGE diets altered the gut microbiota composition and structure, and induced insulin resistance in mice. In the pathogenesis of insulin resistance, the loss of butyrate-producing bacteria might impair the colonic epithelial barrier, thereby triggering chronic low-grade inflammation.

Relationship between serum lipopolysaccharide binding protein levels, disease activity, and clinical characteristics in Paraguayan patients with systemic lupus erythematosus.

Systemic exposure to bacterial components like lipopolysaccharide (LPS) is among the non-genetic factors that could be involved in the onset or progression of systemic lupus erythematosus (SLE). Lipopolysaccharide-binding protein (LBP) participates in the recognition of LPS and in the inflammatory response. Here, we investigated LBP in SLE patients and its relationship with disease activity and SLE phenotypes. Eighty-one adult patients with SLE from IMID-PY biobank (Paraguay) were included in the study. The clinical and laboratory variables were used to determine SLE activity. LBP levels were determined by ELISA in SLE patients and age- and sex-matched population-based controls. Patients with SLE have lower levels of circulating LBP compared to healthy controls (p = 0.0007). No significant correlation was found between serum LBP levels and disease activity. A significant difference was observed in LBP levels with regard to the presence of arthritis (p = 0.026). No other relation was found with clinical parameters. We found low levels of LBP in SLE patients compared to the control group. No correlation was detected between LBP levels and disease activity. It would be interesting for future studies to evaluate the impact of low levels of LBP on lupus immunopathogenesis.

Clinical impact of antibodies to Sp100 on a bacterial infection in patients with primary biliary cholangitis.

BackgroundA specific antinuclear antibody for primary biliary cholangitis (PBC) is anti‐Sp100, which was recognized as a serological marker of concurrent urinary tract infection. We sought to determine the clinical characteristics of PBC patients who had anti‐Sp100.Patients and MethodsFifty‐one patients with PBC and 10 healthy controls (HCs) were enrolled. Anti‐Sp100 were determined with an ELISA method. Lipopolysaccharide‐binding protein (LBP) was measured as a serological hallmark for bacterial infection. The correlations of anti‐Sp100 with demographic, laboratory, and pathological parameters were investigated.ResultsSix of the 51 (11.8%) PBC patients had anti‐Sp100, whereas none of the HCs did. There was no significant difference in the frequency of antimitochondrial antibodies (AMAs) between PBC patients with and without anti‐Sp100 (67% vs. 82%, p = 0.5839). Biochemical and immunological parameters were not associated with the emergence of anti‐Sp100 in these patients. The clinical stage by Scheuer classification was not correlated with the existence of anti‐Sp100. No significant difference in the serum LBP levels was found between PBC patients with and without anti‐Sp‐100, although serum LBP levels were significantly higher in PBC patients with anti‐Sp100 than in HCs (8.30 ± 2.24 ng/ml, vs. 5.12 ± 2.48 ng/ml, p = 0.0022). The frequency of granuloma formation was higher in the liver specimens of PBC patients with anti‐Sp100 than in those without anti‐Sp100 (67% vs 29%, p = 0.0710).Conclusionanti‐Sp100 does not become a complementary serological marker for PBC in AMA‐negative patients. A bacterial infection may trigger the production of anti‐Sp100. Another factor is required to initiate the autoantibody production.

Roux-en-Y Gastric Bypass Improved Insulin Resistance via Alteration of the Human Gut Microbiome and Alleviation of Endotoxemia.

Background Obesity is a main contributing factor for the development of glucose intolerance and type 2 diabetes mellitus (T2D). Roux-en-Y gastric bypass (RYGB) is believed to be one of the most effective treatments to reduce body weight and improve glucose metabolism. In this study, we sought to explore the underlying mechanisms of weight reduction and insulin resistance improvement after RYGB. Methods This was a prospective observational study using consecutive samples of 14 obese subjects undergoing bariatric surgery. Main assessments were serum indexes (blood metabolites, glucose-lipid regulating hormones, trimethylamine-N-oxide (TMAO), and lipopolysaccharide-binding protein (LBP), fecal short-chain fatty acids (SCFAs), and gut microbiota. Correlation analysis of the factors changed by RYGB was used to indicate the potential mechanism by which surgery improves insulin resistance. Results The subjects showed significant improvement on indices of obesity and insulin resistance and a correlated change of gut microbiota components at 1 month, 3 months, and 6 months post-RYGB operation. In particular, the abundance of a counterobese strain, Akkemansia muciniphila, had gradually increased with the postoperative time. Moreover, these changes were negatively correlated to serum levels of LBP and positively correlated to serum TMAO and fecal SCFAs. Conclusions Our findings uncovered links between intestinal microbiota alterations, circulating endotoxemia, and insulin resistance. This suggests that the underlying mechanism of protection of the intestine by RYGB in obesity may be through changing the gut microbiota.