Lipopolysaccharide-binding Protein Research Articles

Concomitant gut dysbiosis and defective gut barrier serve as the bridges between hypercortisolism and chronic systemic inflammation in Cushing disease.

The aim of this study was to investigate the gut microbial signatures and related pathophysiological implications in patients with Cushing's disease (CD). 27 patients with CD and 45 healthy controls were enrolled. Based on obtained metagenomics data, we performed correlation, network study and genome interaction group (GIG) analysis. Fecal metabolomics and serum ELISA analysis were conducted in dichotomized CD patients. Caco-2 cells were incubated with gradient concentrations of cortisol for subsequent transepithelial electrical resistance (TEER) measurement, FITC-dextran transwell permeability assay, qPCR and western blot analysis. Gut microbial composition in patients with CD was notably different from that in healthy controls. Network analysis revealed that Eubacterium siraeum might serve as the core specie in the gut microbial system of CD patients. Subsequent GIG analysis identified the positive correlations between GIG9 and UFC. Further serum ELISA and fecal metabolomics uncovered that CD patients with elevated UFC levels were characterized with increased lipopolysaccharide binding protein (LBP). Moreover, remarkable positive association was found between LBP level and relative abundance of Eubacterium siraeum. TEER and FITC-Dextran transwell assays demonstrated that hypercortisolism induced increased gut permeability. Further qPCR and western blot analysis suggested that dysregulated AhR/Claudin 2 axis might be involved in the development of hypercortisolism-induced defective gut barrier function. Disease activity associated dysbiosis and defective gut barrier might jointly facilitate the development of systemic inflammation in patients with CD.

Effect of the Mediterranean diet on the fecal long-chain fatty acid composition and intestinal barrier integrity: An exploratory analysis of the randomized controlled LIBRE trial.

We recently showed that adherence to the Mediterranean diet increased the proportion of plasma omega-3 polyunsaturated fatty acids (n-3 PUFAs), which was associated with an improved intestinal barrier integrity. In the present exploratory analysis, we assessed fecal fatty acids in the same cohort, aiming to investigate possible associations with intestinal barrier integrity. Women from the LIBRE randomized controlled trial, characterized by an impaired intestinal barrier integrity, followed either a Mediterranean diet (intervention group, IG, n=33) or a standard diet (control group, CG, n=35). At baseline (BL), month 3 (V1), and month 12 (V2), plasma lipopolysaccharide binding protein (LBP), fecal zonulin, and fecal fatty acids were measured. In the IG, fecal proportions of palmitoleic acid (16:1, n-7) and arachidonic acid (20:4, n-6) decreased, while the proportion of linoleic acid (18:2, n-6) and alpha linoleic acid (18:3, n-3) increased (BL-V1 and BL-V2, all P<0.08). In the CG, fecal proportions of palmitic acid and arachidic acid increased while the proportion of linoleic acid decreased (BL-V1, all P<0.05). The decrease in the proportion of palmitoleic acid correlated with the decrease in plasma LBP (∆V1-BL r=0.72, P<0.001; ∆V2-BL r=0.39, P<0.05) and correlated inversely with adherence to the Mediterranean diet (Mediterranean diet score; ∆V1-BL r=-0.42, P=0.03; ∆V2-BL r=-0.53, P=0.005) in the IG. Our data show that adherence to the Mediterranean diet induces distinct changes in the fecal fatty acid composition. Furthermore, our data indicate that the fecal proportion of palmitoleic acid, but not fecal n-3 PUFAs, are associated with intestinal barrier integrity in the IG.

Factors Promoting Lipopolysaccharide Uptake by Synthetic Lipid Droplets.

Lipoproteins are essential in removing lipopolysaccharide (LPS) from blood during bacterial inflammation. The physicochemical properties of lipoproteins and environmental factors can impact LPS uptake. In this work, synthetic lipid droplets containing triglycerides, cholesterols, and phospholipids, were prepared to mimic lipoproteins. The physicochemical properties of these lipid droplets, such as charges, sizes, and lipid compositions, were altered to understand the underlying factors affecting LPS uptake. The amphiphilic LPS could spontaneously adsorb on the surface of lipid droplets without lipopolysaccharide binding protein (LBP); however, the presence of LBP can increase LPS uptake. The positively charged lipid droplets also enhance the uptake of negatively charged LPS. Most interestingly, the LPS uptake highly depends on the concentrations of Ca 2+ near the physiological conditions, but the impact of Mg 2+ ions was not significant. The increase of Ca 2+ ions can improve LPS uptake by lipid droplets; this result suggested that Ca 2+ may play an essential role in LPS clearance. Since septic shock patients typically suffer from hypocalcemia and low levels of lipoproteins, the supplementation of Ca 2+ ions along with synthetic lipoproteins may be a potential treatment for severe sepsis.

Sportomics Analyses of the Exercise-Induced Impact on Amino Acid Metabolism and Acute-Phase Protein Kinetics in Female Olympic Athletes

Background: Exercise can be used as a model to understand immunometabolism. Biological data on elite athletes are limited, especially for female athletes, including relevant data on acute-phase proteins and amino acid metabolism. Methods: We analyzed acute-phase proteins and amino acids collected at South American, Pan-American, and Olympic Games for 16 Olympic sports. We compared female and male elite athletes (447 vs. 990 samples) across four states (fasting, pre-exercise, post-exercise, and resting) to understand sex-specific immunometabolic responses in elite athletes. Results: Considering all states and sports, we found that elite female athletes exhibited higher concentrations of C-reactive protein, lipopolysaccharide-binding protein, myeloperoxidase, haptoglobin, and IGF1, with ratios ranging from 1.2 to 2.0 (p &lt; 0.001). Women exhibited lower concentrations of most amino acids, except for glutamate and alanine. Although almost 30% lower in women, branched-chain amino acids (BCAAs) showed a similar pattern in all states (ρ ≥ 0.9; p &lt; 0.001), while aromatic amino acids (AAAs) showed higher consumption during exercise in women. Conclusion: We established sex dimorphism in elite athletes’ metabolic and inflammatory responses during training and competition. Our data suggest that female athletes present a lower amino acid response towards central fatigue development than male athletes. Understanding these differences can lead to insights into sex-related immuno-metabolic responses in sports or other inflammatory conditions.

Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults.

We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32±3 years) and nine older (72±3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11±0.11), but the excretion of sucrose was increased only in older adults (Δ1.7±1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65±0.89µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08±0.07mg/dL), cystatin C (group-wide: Δ0.16±0.18mg/L) and urinary IGFBP7×TIMP-2 [group-wide: Δ0.64±0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age.

The impact of exogenous vasoactive intestinal polypeptide (VIP) on inflammatory responses and mRNA expression of tight junction genes in lambs fed a high-grain diet.

This study assessed the impact of administering vasoactive intestinal polypeptide (VIP) on inflammation and intestinal VIP and tight junction mRNA expression in lambs fed grain-based finishing diets. Sixteen wether lambs (69.6 ± 1.9kg) were individually housed, adapted to a corn-based diet containing no forage, and randomly assigned to 2 treatment groups. Lambs were intraperitoneally injected every other day for 28 d with either saline (0.9% NaCl) with no VIP (n = 8; control) or saline with VIP (n = 8; 1.3 nmol/kg BW). Blood samples were collected weekly for analysis of cytokine concentrations, and on day 0 and 28 for lipopolysaccharide (LPS), and LPS binding protein (LBP) concentrations. Upon completion of the treatment period, lambs were euthanized and gastrointestinal tissues, including rumen, jejunum, cecum, and colon samples, collected for analysis of the expression of tight junction mRNA (claudin-1, claudin-4, occludin, and ZO-1), endogenous VIP, and VIP receptor (VPAC-1). No treatment effects (P ≥ 0.38) were observed for VIP and VPAC-1 mRNA expression in colon. Supplementation with VIP did not influence (P ≥ 0.28) the expression of claudin-1, claudin-4, occludin, and ZO-1 tight junction mRNA in the rumen, jejunum, cecum, and colon. Lambs treated with VIP had greater (P ≤ 0.01) plasma concentrations of the anti-inflammatory cytokines, IL-10 and IL-36RA. There were treatment by day interactions observed (P ≤ 0.02) for concentrations of the proinflammatory cytokines, MIP-1α and MIP-1β. Lambs that did not receive VIP had greater serum concentrations of LPS (P = 0.05) than the lambs receiving VIP. These data suggest that VIP administration may not influence tight junction mRNA expression but may decrease LPS concentrations and thus inflammation in lambs fed a grain-based diet.

Marine macroalgae Chaetomorpha aerea as a dietary supplement: Optimizing immunity and resistance to Edwardsiella tarda in tilapia (Oreochromis mossambicus)

The intensification of aquaculture has led to a rise in fish infections, necessitating the search for alternative antibiotics. In this context, our study investigated the effects of dietary supplementation with Chaetomorpha aerea, a filamentous green algae, on the immune health and resistance to infections in tilapia (Oreochromis mossambicus). Diets containing varying concentrations of C. aerea (0, 1, 2, 5, and 10 g/kg) were prepared and administered to the fish for 30 days, followed by a challenge with Edwardsiella tarda to evaluate survival rates. The results were significant. The diet containing 5 g/kg of C. aerea (group T3) brought about substantial improvements in hematological parameters, including increases in red blood cell count (RBC), hematocrit (Hct), and hemoglobin (Hb). The T3 group exhibited a robust immune response, with higher lysozyme and ceruloplasmin activity in immunological assays. LBP gene expression was significantly elevated in the spleen and thymus of fish in the T3 group, which correlated with higher survival after bacterial challenge compared to the control group. Principal Component Analysis (PCA) and cluster analysis confirmed that the 5 g/kg concentration stood out for maximizing immunological benefits without compromising the overall health of the fish. These findings highlight the robust immune response in the T3 group, a key finding of our study. We conclude that supplementation with C. aerea represents a promising and sustainable alternative in the formulation of diets for tilapia, contributing to improved health and resistance to diseases. Future studies are recommended to explore its application in other species and development stages, in addition to evaluating other health biomarkers.

Dietary thiamine supplementation modulates ruminal microbiota and partly restores lactation performance in lactating Hu ewes under heat-stress conditions

This study aimed to investigate the impact of dietary thiamine supplementation on milk production, rumen microbiota profile and inflammatory response of Hu ewes under heat-stress conditions. Twenty-seven multiparous pregnant and lactating Hu ewes of 71.6 ± 1.4 kg body weight, 11 ± 0.5 months gestation age, 31 ± 1 days in milk, 1.68 ± 0.15 L/d milk yield, and 2.14 ± 0.12 kg of daily dry matter intake (DMI), were used in the study. Following an acclimation period of 7 days, ewes were divided into 3 blocks of 9 each (one Hu ewe per pen), in a complete randomized design and assigned to one of three environmental temperature conditions for 15 days: thermoneutrality without supplementation (CON), heat-stressed without supplementation (HS) or heat-stressed with dietary thiamine supplementation (200 mg/kg of DMI; HST). The results indicated that the HS group experienced notable declines in milk protein, fat, and lactose content from day 10–15 (P < 0.05) compared to the CON group. In contrast, thiamine supplementation significantly elevated milk protein content from day 13–15 and raised milk fat and lactose content on days 14 and 15 (P < 0.05) compared to the HS group, thereby enhancing milk quality to a certain extent. Additionally, thiamine supplementation (HST group) significantly increased the circulating thiamine and Immunoglobulin A (IgA) concentrations accompanied by a significant decline in LPS-binding protein, interleukin-1 (IL-1), and serum amyloid A protein (SAA) levels compared to the HS group (P < 0.05). Rumen microbial composition analysis revealed that thiamine supplementation increased the abundance of Pyramidobacter, Butyrivibrio, Bacteroides, and Saccharofermentans. In conclusion, heat exposure during lactation in Hu ewes lowered milk production and quality, affecting rumen microbes. Dietary thiamine supplementation could improve rumen fermentation, mitigate heat stress-induced inflammation, and restore milk production in Hu ewes under heat stress conditions.

Visceral adiposity in postmenopausal women is associated with a pro-inflammatory gut microbiome and immunogenic metabolic endotoxemia

BackgroundObesity, and in particular abdominal obesity, is associated with an increased risk of developing a variety of chronic diseases. Obesity, aging, and menopause are each associated with differential shifts in the gut microbiome. Obesity causes chronic low-grade inflammation due to increased lipopolysaccharide (LPS) levels which is termed “metabolic endotoxemia.” We examined the association of visceral adiposity tissue (VAT) area, circulating endotoxemia markers, and the gut bacterial microbiome in a cohort of aged postmenopausal women.MethodsFifty postmenopausal women (mean age 78.8 ± 5.3 years) who had existing adipose measurements via dual x-ray absorptiometry (DXA) were selected from the extremes of VAT: n = 25 with low VAT area (45.6 ± 12.5 cm2) and n = 25 with high VAT area (177.5 ± 31.3 cm2). Dietary intake used to estimate the Healthy Eating Index (HEI) score was assessed with a food frequency questionnaire. Plasma LPS, LPS-binding protein (LBP), anti-LPS antibodies, anti-flagellin antibodies, and anti-lipoteichoic acid (LTA) antibodies were measured by ELISA. Metagenomic sequencing was performed on fecal DNA. Female C57BL/6 mice consuming a high-fat or low-fat diet were treated with 0.4 mg/kg diet-derived fecal isolated LPS modeling metabolic endotoxemia, and metabolic outcomes were measured after 6 weeks.ResultsWomen in the high VAT group showed increased Proteobacteria abundance and a lower Firmicutes/Bacteroidetes ratio. Plasma LBP concentration was positively associated with VAT area. Plasma anti-LPS, anti-LTA, and anti-flagellin IgA antibodies were significantly correlated with adiposity measurements. Women with high VAT showed significantly elevated LPS-expressing bacteria compared to low VAT women. Gut bacterial species that showed significant associations with both adiposity and inflammation (anti-LPS IgA and LBP) were Proteobacteria (Escherichia coli, Shigella spp., and Klebsiella spp.) and Veillonella atypica. Healthy eating index (HEI) scores negatively correlated with % body fat and anti-LPS IgA antibodies levels. Preclinical murine model showed that high-fat diet-fed mice administered a low-fat diet fecal-derived LPS displayed reduced body weight, decreased % body fat, and improved glucose tolerance test parameters when compared with saline-injected or high-fat diet fecal-derived LPS-treated groups consuming a high-fat diet.ConclusionsIncreased VAT in postmenopausal women is associated with elevated gut Proteobacteria abundance and immunogenic metabolic endotoxemia markers. Low-fat diet-derived fecal-isolated LPS improved metabolic parameters in high-fat diet-fed mice giving mechanistic insights into potential pro-health signaling mediated by under-acylated LPS isoforms.7yVbQmTTfsF9b4Af3tznWNVideo

Low-grade systemic inflammation in patients with long COVID: The role of imbalance of endotoxin-releasing systems and vasoconstrictor markers

Background. Currently, the pathophysiological mechanisms of acute damage to organs and systems caused by coronavirus infection have been studied quite fully, but the mechanisms underlying the clinical manifestations of long COVID have not yet been accurately described. The mechanisms of persistence of a number of symptoms in patients who have had COVID-19 and the role of systemic inflammation and endotoxemia markers in it remain a understudied aspect and a promising direction for further studying.The aim of the study. To assess the markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability and endothelial dysfunction in patients with long COVID at the stage of health resort treatment.Methods. The study included 32 patients who had recovered from coronavirus infection and were undergoing health resort treatment in the pulmonology department of the I.M. Sechenov Academic Research Institute for Physical Therapy, Medical Climatology and Rehabilitation. We also selected a control group (n = 20). All patients underwent peripheral blood analysis to detect the levels of markers of systemic inflammation, endotoxin-releasing systems, intestinal permeability, endothelial dysfunction and vasoconstrictor agents: C-reactive protein (CRP), lipopolysaccharide-binding protein (LPB), tissue-type plasminogen activator (tPA), zonulin, bactericidal/ permeability-increasing protein (BPI), vasopressors of angiotensin 2 and endothelin (EDN1).Results. Patients who had recovered from coronavirus infection had a statistically significant increase in the levels of CRP (3.4 [2.56; 4.0] mg/l), LBP (18.46 [14.0; 25.5] ng/ml), tPA (0.07 [0.02; 0.32] ng/ml), angiotensin 2 (133.3 [63.0; 503.7] pg/ml) and a decrease in the level of BPI (1576 [276; 3588] pg/ml) (p &lt; 0.05).Conclusion. A statistically significant increase in markers of systemic inflammation, endotoxinemia, and vasoconstrictor agents in patients with long COVID indicates an imbalance in endotoxin-binding and endotoxin-releasing systems in patients who have had coronavirus infection. Further study of the described markers is necessary to improve approaches to long-term personalized therapy for this category of patients.

Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.

This study aimed to assess plasma galectin-9 (Gal-9) and artemin (ARTN) concentrations as potential biomarkers to differentiate individuals with Long COVID (LC) patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) from SARS-CoV-2 recovered (R) and healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis determined a cut-off value of plasma Gal-9 and ARTN to differentiate LC patients from the R group and HCs in two independent cohorts. Positive correlations were observed between elevated plasma Gal-9 levels and inflammatory markers (e.g. SAA and IP-10), as well as sCD14 and I-FABP in LC patients. Gal-9 also exhibited a positive correlation with cognitive failure scores, suggesting its potential role in cognitive impairment in LC patients with ME/CFS. This study highlights plasma Gal-9 and/or ARTN as sensitive screening biomarkers for discriminating LC patients from controls. Notably, the elevation of LPS-binding protein in LC patients, as has been observed in HIV infected individuals, suggests microbial translocation. However, despite elevated Gal-9, we found a significant decline in ARTN levels in the plasma of people living with HIV (PLWH). Our study provides a novel and important role for Gal-9/ARTN in LC pathogenesis.

Evaluation of circulating immune cells, analytes, and inflammatory markers in sows affected with postpartum dysgalactia syndrome.

Postpartum dysgalactia syndrome (PDS) is a condition affecting periparturient sows, characterized by a reduction in milk and colostrum synthesis shortly after farrowing. Insufficient milk production results in substantial economic losses due to increased piglet morbidity/mortality and premature sow culling. Since PDS develops within a few days following farrowing, the study objectives were to determine if periparturient immune cell profiles and circulating biomarkers differ in sows affected by PDS. We hypothesized differences in immune cells, circulating analytes, and inflammatory markers would exist at farrowing in sows that subsequently developed PDS compared to healthy herd-mates. Thirty-six sows with PDS symptoms were matched by parity and day of lactation with 36 healthy control (CON) sows. Diagnosis of PDS (timepoint 2) occurred on average 9.25 ± 2.67 d after farrowing. Blood samples and litter weights were collected at farrowing (timepoint 1) and at the onset of clinical PDS (timepoint 2). Piglets from PDS sows had lower average daily gain and higher mortality than piglets from CON (P < 0.01). Aspartate aminotransferase was increased (20%; P ≤ 0.06) in PDS sows compared to CON at both timepoints. Additionally, blood urea nitrogen was increased in PDS sows at timepoint 1 and timepoint 2 (13%; P = 0.08 and 16%; P = 0.01, respectively). At timepoint 2, total protein, globulin, magnesium, and cholesterol were increased (P ≤ 0.03) while γ-glutamyl transferase and albumin were decreased (P ≤ 0.02) in PDS sows. Lipopolysaccharide-binding protein, an inflammatory biomarker, was increased (48%; P = 0.07) at timepoint 2 in PDS compared to CON sows. Collectively, these data indicate PDS sows have altered metabolism and appear immune activated compared to healthy herd-mates, and further investigation is needed to determine if PDS can be predicted at farrowing.

Effects of Cashew Nuts (Anacardium occidentale L.) and Cashew Nut Oil on Intestinal Permeability and Inflammatory Markers during an Energy-Restricted 8-Week Intervention: A Randomized Controlled Trial (Brazilian Nuts Study).

Cashew nuts can contribute to improving intestinal permeability and inflammation as they contain essential nutrients and bioactive compounds, but no clinical trials have evaluated these potential effects. This randomized trial aimed to assess the effects of cashew nuts and their oil on intestinal permeability and inflammatory markers. Sixty-four adults with overweight or obesity were allocated into three groups receiving energy restriction (-500 kcal/day): control (CT, free nuts), cashew nuts (CN, 30 g/day), or cashew nut oil (OL, 30 mL/day). Urine lactulose and mannitol, plasma zonulin and the lipopolysaccharide-binding protein (LBP), plasma interleukins (IL-6, TNF-α, IL-10, IL-1β, IL-8, and IL-12p70), and C-reactive proteins were analyzed. Energy restriction reduced body fat and other indicators of adiposity without differences between the groups. Only the control group increased LBPs after an 8-week intervention. There were no statistically significant differences found between the groups in terms of intestinal permeability and inflammatory markers. In conclusion, incorporating cashew nuts or cashew nut oil into an energy-restricted 8-week dietary intervention did not change intestinal permeability and inflammatory markers. As studies evaluating cashew nuts on these markers remain scarce, further research is needed, perhaps with a longer study period and a higher concentration of cashew nuts and oil.

Intestinal fatty acid binding protein is associated with infarct size and cardiac function in acute heart failure following myocardial infarction

BackgroundIn acute heart failure (HF), reduced cardiac output, vasoconstriction and congestion may damage the intestinal mucosa and disrupt its barrier function. This could facilitate the leakage of bacterial products into...

Gut-related molecules as potential biomarkers in patients with decompensated cirrhosis

Introduction and ObjectivesMicrobial translocation contributes to cirrhosis progression and complications. This study aims to investigate whether molecules related to intestinal permeability or microbial translocation can serve as prognostic biomarkers in patients with decompensated cirrhosis. Materials and MethodsWe prospectively evaluated hospitalized patients with decompensated cirrhosis for liver function, complications during hospitalization, in-hospital mortality, composite outcomes of in-hospital mortality and complications, 12-month mortality, and survival rates. Blood samples were collected upon admission, and 1,3 beta-d-glucan, zonulin, calprotectin, and lipopolysaccharide-binding protein were measured using commercial kits. ResultsNinety-one patients with decompensated cirrhosis were enrolled. The mean age was 58 ± 12 years; 57% were male. The three main cirrhosis etiologies were hepatitis C (35%), alcohol (25%), and non-alcoholic steatohepatitis (17%). In terms of liver function, 52% were Child C, and 68% had model for end-stage liver disease ≥15. The in-hospital and one-year mortality rates were 31% and 57%, respectively. Child-Pugh, 1,3 beta-glucan, and model for end-stage liver disease were positively correlated; zonulin was associated with complications during hospitalization (acute kidney injury) and composite outcomes, and calprotectin was associated with all outcomes except 12-month mortality. ConclusionsSerum calprotectin and zonulin levels emerge as noninvasive prognostic biomarkers for potentially unfavorable outcomes in patients with decompensated cirrhosis.

The Potential of Eight Plasma Proteins as Biomarkers in Redefining Leptospirosis Diagnosis.

Leptospirosis, a notifiable endemic disease in Malaysia, has higher mortality rates than regional dengue fever. Diverse clinical symptoms and limited diagnostic methods complicate leptospirosis diagnosis. The demand for accurate biomarker-based diagnostics is increasing. This study investigated the plasma proteome of leptospirosis patients with leptospiraemia and seroconversion compared with dengue patients and healthy subjects using isobaric tags for relative and absolute quantitation (iTRAQ)-mass spectrometry (MS). The iTRAQ analysis identified a total of 450 proteins, which were refined to a list of 290 proteins through a series of exclusion criteria. Differential expression in the plasma proteome of leptospirosis patients compared to the control groups identified 11 proteins, which are apolipoprotein A-II (APOA2), C-reactive protein (CRP), fermitin family homolog 3 (FERMT3), leucine-rich alpha-2-glycoprotein 1 (LRG1), lipopolysaccharide-binding protein (LBP), myosin-9 (MYH9), platelet basic protein (PPBP), platelet factor 4 (PF4), profilin-1 (PFN1), serum amyloid A-1 protein (SAA1), and thrombospondin-1 (THBS1). Following a study on a verification cohort, a panel of eight plasma protein biomarkers was identified for potential leptospirosis diagnosis: CRP, LRG1, LBP, MYH9, PPBP, PF4, SAA1, and THBS1. In conclusion, a panel of eight protein biomarkers offers a promising approach for leptospirosis diagnosis, addressing the limitations of the "one disease, one biomarker" concept.

Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD.

Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD.

Biomarkers of Intestinal Permeability are Associated with Inflammation in Metabolically Healthy Obesity, but not Normal-Weight Obesity.

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota) - and their relationships with measured inflammation - in NWO and MHO, healthy controls (CON) and metabolically unhealthy obesity (MUO; N=80; n=20/group). Serum indicators of intestinal permeability and inflammation were assessed using ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n=9-10/group). For C-reactive protein (CRP), MUO > NWO > CON (p<0.0001). In MHO, CRP was intermediate - and similar to - both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO versus CON/NWO (p's<0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r=0.78;β = 0.57;p's<0.0001) and in MHO (r=0.74;p<0.01), but not NWO (r=0.37;p = 0.11). Shannon index was higher in CON compared to MUO (p<0.05) and inversely correlated with CRP in the full sample (r=-0.37;p<0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk.

Thiamine deficiency underlies persistent gut dysbiosis and inflammation in people living with HIV on antiretroviral therapy

BackgroundAntiretroviral therapy (ART) has significantly improved the prognosis for people living with human immunodeficiency virus (PLWH). However, alterations in the gut microbiota of PLWH affect their metabolic environment and may contribute to chronic inflammation and premature aging, despite effective ART. Given that inflammation in the body have been shown to be risk factors for age-related diseases, elucidating changes in the gut microbiota and metabolic levels over time in individuals would be for understanding the dynamics in the body that lead to disease development.MethodsThe study assessed changes in blood markers, gut microbiota, and metabolic environment of PLWH on ART for four years, with participants divided into two groups based on median CD4 cell count (580/µL).ResultsThe high-CD4 group was more obese than the low-CD4 group, but there was no significant difference in comorbidities, such as diabetes, hypertension, and dyslipidemia. An investigation of the alterations in gut microbiota over a 4-year period revealed a reduction in specific groups of bacteria that produce short-chain fatty acids (SCFAs) and an increase in the occurrence of Enterobacteriaceae. In addition, a decline in bacterial thiamine synthesis was predicted, and a decreased abundance of the Ruminococcus gauvreauii group, which relies on supplementation with thiamine from symbiotic bacteria, was observed. The abundance of Collinsella and Catenibacterium at baseline was positively correlated with the predicted number of thiamine-synthesizing pathway. The presence of Catenibacterium at follow-up was inversely correlated with the rate of increase in plasma levels of lipopolysaccharide-binding protein, an indicator of a leaky gut. In terms of assessing the diversity of gut microbiota, a trend towards an increase in opportunistic bacteria with different genetic distances was observed in the high-CD4 group at follow-up.ConclusionThese observations suggested that, despite effective ART, the thiamine-deficient environment in the gut continues to reduce thiamine-requiring bacteria, such as certain SCFA-producing bacteria. As a result, secondary effects, such as proliferation of opportunistic bacteria and chronic inflammation associated with increased intestinal permeability, proceed in PLWH. Thus, certain essential nutrient deficiencies for gut metabolic environment may disrupt the symbiotic relationship between gut bacteria and increase the risk of developing inflammatory diseases.

Proatherogenic proteomic profile of LDL isolated from plasma of patients with diabetes mellitus: immunological aspects

Atherosclerosis is a vascular disease, which is based on a chronic inflammatory process, including complex interactions between blood components, as well as the cells that form the vessel wall, and lipid metabolism in general. Low-density lipoproteins (LDL) play a key role in pathogenesis of atherosclerosis. When the permeability of the endothelial layer of the vessel is impaired, LDL can penetrate into the intramural space and lead to excessive cholesterol accumulation by the cells from the intima subendothelial layer, leading to the onset of the inflammatory process and to the formation of foam cells, the main morphological component of the atherosclerotic plaque. However, the level of LDL in the patient’s blood plasma alone is not a key indicator of the development of atherosclerosis. Numerous studies point out the role of oxidized modifications of LDL (oxLDL) in the increased local accumulation of cholesterol in vascular wall cells, however, recent works have shown conflicting results regarding the role of oxLDL in the development of atherosclerosis. We hypothesize that other components of LDL may also influence the progression of atherosclerosis. It is a well-known fact that patients with diabetes mellitus (DM) suffer from cardiovascular diseases, in particular atherosclerosis, more often than patients without diagnosed DM and other autoimmune diseases, and the disease progresses faster. The purpose of this study was to identify risk biomarkers in LDL groups that indicate the relationship of the immune system with the development of atherosclerosis in such patients. LDL was isolated from patients and healthy donors using continuous ultracentrifugation with solutions of different densities, and LDL protein profile samples were measured using gas chromatography-mass spectrometry. We found 9 proteins that had a statistically significant difference between the samples (DM and control). In the diabetes group, the content of the antimicrobial peptide cathelicidin and lipopolysaccharide-binding protein was almost 2 times higher compared to the control. These proteins may be involved in the development of inflammation, leading to the progression of atherosclerosis. At the same time, a decrease in immunoglobulins and complement components (C9 and Complement C1s subcomponent) associated with LDL may contribute to the development of atherosclerosis.