Plasma Lipopolysaccharide Concentration Research Articles

Diffusion magnetic resonance spectroscopy captures microglial reactivity related to gut-derived systemic lipopolysaccharide: A preliminary study

Neuroinflammation is a key component underlying multiple neurological disorders, yet non-invasive and cost-effective assessment of in vivo neuroinflammatory processes in the central nervous system remains challenging. Diffusion weighted magnetic resonance spectroscopy (dMRS) has shown promise in addressing these challenges by measuring diffusivity properties of different neurometabolites, which can reflect cell-specific morphologies. Prior work has demonstrated dMRS utility in capturing microglial reactivity in the context of lipopolysaccharide (LPS) challenges and serious neurological disorders, detected as changes of microglial metabolite diffusivity properties. However, the extent to which such dMRS metrics are capable of detecting subtler and more nuanced levels of neuroinflammation in populations without overt neuropathology is unknown. Here we examined the relationship between intrinsic, gut-derived levels of systemic LPS and dMRS-based apparent diffusion coefficients (ADC) of choline, creatine, and N-acetylaspartate (NAA) in two brain regions: the thalamus and the corona radiata. Higher plasma LPS concentrations were significantly associated with increased ADC of choline and NAA in the thalamic region, with no such relationships observed in the corona radiata for any of the metabolites examined. As such, dMRS may have the sensitivity to measure microglial reactivity across populations with highly variable levels of neuroinflammation, and holds promising potential for widespread applications in both research and clinical settings.

Anti-steatotic effects of PPAR-alpha and gamma involve gut-liver axis modulation in high-fat diet-fed mice

AimTo evaluate the effects of PPARα and PPARγ activation (alone or in combination) on the gut-liver axis, emphasizing the integrity of the intestinal barrier and hepatic steatosis in mice fed a high saturated fat diet. MethodsMale C57BL/6J were fed a control diet (C) or a high-fat diet (HF) for ten weeks. Then, a four-week treatment started: HF-α (WY14643), HF-γ (low-dose pioglitazone), and HF-αγ (combination). ResultsThe HF caused overweight, insulin resistance, impaired gut-liver axis, and marked hepatic steatosis. Treatments reduced body mass, improved glucose homeostasis, and restored the gut microbiota diversity and intestinal barrier gene expression. Treatments also lowered the plasma lipopolysaccharide concentrations and favored beta-oxidation genes, reducing macrophage infiltration and steatosis in the liver. ConclusionTreatment with PPAR agonists modulated the gut microbiota and rescued the integrity of the intestinal barrier, alleviating hepatic steatosis. These results show that these agonists can contribute to metabolic-associated fatty liver disease treatment.

Relationship between Plasma Lipopolysaccharide Concentration and Health Status in Healthy Subjects and Patients with Abnormal Glucose Metabolism in Japan: A Preliminary Cross-Sectional Study

Lipopolysaccharides are components of Gram-negative bacteria. The relationship between blood lipopolysaccharide levels and health status has mainly been investigated in Europe, and there is a lack of information about Asia, particularly Japan. This study aimed to investigate the relationship between blood lipopolysaccharide levels and health status in the Japanese. We conducted two cross-sectional studies in 36 healthy subjects (Study 1) and 36 patients with abnormal glucose metabolism (AGM; Study 2). The plasma lipopolysaccharide concentration in healthy subjects was positively correlated with body mass index. The plasma lipopolysaccharide concentration in AGM patients was obviously higher than that in healthy subjects. Furthermore, in AGM patients, the plasma lipopolysaccharide concentration was positively correlated with C-peptide, fasting plasma glucose levels, triglycerides, and stage of diabetic nephropathy. The plasma lipopolysaccharide concentration was also negatively correlated with 20/(C-peptide × fasting plasma glucose), an indicator of insulin resistance, and high-density lipoprotein cholesterol. In particular, the correlation between plasma lipopolysaccharide concentration and triglycerides in AGM patients was maintained in multiple regression analyses adjusted for age, sex, or body mass index. These results suggest a possible role of lipopolysaccharides in obesity in healthy subjects and in the deterioration of triglyceride metabolism in AGM patients in the Japanese population.

Metformin, Cognitive Function, and Changes in the Gut Microbiome.

The decline in cognitive function and the prevalence of neurodegenerative disorders are among the most serious threats to health in old age. The prevalence of dementia has reached 50 million people worldwide and has become a major public health problem. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced risk of cognitive impairment and dementia. Human studies have shown that patients with T2D exhibit dysbiosis of the gut microbiota. This dysbiosis may contribute to the development of insulin resistance and increased plasma lipopolysaccharide concentrations. Metformin medication mimics some of the benefits of calorie restriction and physical activity, such as greater insulin sensitivity and decreased cholesterol levels, and hence may also have a positive impact on aging in humans. According to recent human investigations, metformin might partially restore gut dysbiosis related to T2D. Likewise, some studies showed that metformin reduced the risk of dementia and improved cognition, although not all studies are concordant. Therefore, this review focused on those human studies describing the effects of metformin on the gut microbiome (specifically the changes in taxonomy, function, and circulating metabolomics), the changes in cognitive function, and their possible bidirectional implications.

Microbial lipopolysaccharide-induced inflammation contributes to cognitive impairment and white matter lesion progression in diet-induced obese mice with chronic cerebral hypoperfusion.

White matter lesions (WMLs) are involved in the pathological processes leading to cognitive decline and dementia. We examined the mechanisms underlying the exacerbation of ischemia-induced cognitive impairment and WMLs by diet-induced obesity, including lipopolysaccharide (LPS)-triggered neuroinflammation via toll-like receptor (TLR) 4. Wild-type (WT) and TLR4-knockout (KO) C57BL/6 mice were fed a high-fat diet (HFD) or low-fat diet (LFD), and subjected to bilateral carotid artery stenosis (BCAS). Diet groups were compared for changes in gut microbiota, intestinal permeability, systemic inflammation, neuroinflammation, WML severity, and cognitive dysfunction. In WT mice, HFD induced obesity and increased cognitive impairment and WML severity compared with LFD-fed mice following BCAS. HFD caused gut dysbiosis and increased intestinal permeability, and plasma LPS and pro-inflammatory cytokine concentrations. Furthermore, HFD-fed mice had higher LPS levels and higher neuroinflammatory status, including increased TLR4 expression, in WMLs. In TLR4-KO mice, HFD also caused obesity and gut dysbiosis but did not increase cognitive impairment or WML severity after BCAS. No difference was found between HFD- and LFD-fed KO mice for LPS levels or inflammatory status in either plasma or WMLs. Inflammation triggered by LPS-TLR4 signaling may mediate obesity-associated exacerbation of cognitive impairment and WMLs from brain ischemia.

Inter-Day Variation in the Fasting Plasma Lipopolysaccharide Concentration in the Morning Is Associated with Inter-Day Variation in Appetite in Japanese Males: A Short-Term Cohort Study

Injection of lipopolysaccharide (LPS), a product of gut bacteria, into the blood increases blood triglycerides and cortisol, an appetite-stimulating hormone. Meanwhile, small amounts of LPS derived from gut bacteria are thought to enter the bloodstream from the gut in daily basis. This study aimed to investigate the effect of LPS influx on appetite or lipid metabolism in humans in everyday life. We measured the fasting plasma LPS concentration before breakfast and the corresponding days' appetite and fat-burning markers for 10 days in four Japanese males (28-31 years) and analyzed the correlation of their inter-day variation. The LPS concentration was negatively correlated with fullness, and positively correlated with the carbohydrate intake. Against our hypothesis, the LPS concentration was positively correlated with the fasting breath acetone concentration, a fat-burning marker. There was a positive correlation between the LPS concentration and fasting body mass index (BMI), but the inter-day variation in BMI was slight. The results suggest that the LPS influx in everyday life is at least associated with appetite in the day.

Intrauterine LPS inhibited arcuate Kiss1 expression, LH pulses, and ovarian function in rats.

Uterine inflammatory diseases are a major cause of infertility in humans and domestic animals. The current findings that intrauterine lipopolysaccharide is absorbed in systemic circulation and attenuates ovarian cyclic activities could provide a basis for developing novel treatments to improve fertility. Uterine inflammatory diseases are a major cause of infertility in humans and domestic animals. Circulating lipopolysaccharide (LPS), a bacterial endotoxin causing uterine inflammation, reportedly downregulates the hypothalamic-pituitary-gonadal axis to mediate ovarian dysfunction. In contrast, the mechanism whereby intrauterine LPS affects ovarian function has not been fully clarified. This study aimed to elucidate whether uterine exposure to LPS downregulates hypothalamic kisspeptin gene (Kiss1) expression, gonadotropin release, and ovarian function. Uterine inflammation was induced by intrauterine LPS administration to ovary-intact and ovariectomized female rats. As a result, plasma LPS concentrations were substantially higher in control rats until 48 h post injection, and the estrous cyclicity was disrupted with a prolonged diestrous phase. Three days post injection, the number of Graafian follicles and plasma estradiol concentration were reduced in LPS-treated rats, while numbers of Kiss1-expressing cells in the anteroventral periventricular nucleus and arcuate nucleus (ARC) were comparable in ovary-intact rats. Four days post injection, ovulation rate and plasma progesterone levels reduced significantly while gene expression of interleukin1β and tumor necrosis factor α was upregulated in the ovaries of LPS-treated rats that failed to ovulate. Furthermore, the number of Kiss1-expressing cells in the ARC and pulsatile luteinizing hormone (LH) release were significantly reduced in ovariectomized rats 24 h post injection. In conclusion, these results indicate that intrauterine LPS is absorbed in systemic circulation and attenuates ovarian function. This detrimental effect might be caused, at least partly, by the inhibition of ARC Kiss1 expression and LH pulses along with an induction of ovarian inflammatory response.

Effects of plasma lipopolysaccharide changes on platelet release of vascular endothelial growth factor and thromobospondin-1 in patients with cirrhotic portal hypertension after TIPS procedure

Objective: To investigate the effects of plasma lipopolysaccharide (LPS) concentration changes on platelet release of vascular endothelial growth factor (VEGF) and thrombospondin (TSP)-1 in patients with decompensated cirrhotic portal hypertension after transjugular intrahepatic portosystemic shunt (TIPS) procedure. Methods: 169 cases with cirrhotic portal hypertension were enrolled, of which 81 cases received TIPS treatment. LPS, VEGF, and TSP-1 concentrations with different Child-Pugh class in peripheral blood plasma of patients were measured. After pre-incubation of normal human platelets with different concentrations of LPS and stimulated by collagen in vitro, platelet PAC-1 expression rate, VEGF, and TSP-1 concentrations were detected. PAC-1 expression rate and the concentrations of LPS, VEGF and TSP-1 in peripheral blood plasma of patients before and after TIPS procedure were detected. The relationship between plasma LPS, VEGF and TSP-1 concentrations and Child-Pugh score changes in patients after TIPS procedure was analyzed. Statistical analysis was performed by t-test, one-way ANOVA or Pearson's rho according to different data. Results: Plasma LPS and TSP-1 concentrations were significantly higher in Child-Pugh class C patients than class A and B, but the concentration of plasma VEGF was significantly lower than class A and B (P < 0.01). In vitro experiments showed that concentration of LPS, TSP-1, and platelet PAC-1 expression rate was higher in the supernatant, but the difference in the concentration of VEGF in the supernatant was not statistically significant. Portal vein pressure and platelet activation were significantly decreased (P < 0.01) in patients after TIPS procedure. Portal venous pressure, platelet activation, plasma LPS, and TSP-1 levels were significantly decreased continuously, while VEGF levels were significantly increased continuously after TIPS procedure. Plasma LPS concentration was positively correlated with TSP-1 concentration (r = 0.506, P < 0.001), and negatively correlated with VEGF concentration (r = -0.167, P = 0.010). Child-Pugh score change range was negatively correlated with change range of plasma VEGF concentration (r = -0.297, P = 0.016), and positively correlated with change range of plasma TSP-1 concentration (r = 0.145, P = 0.031) after TIPS. Conclusion: Portal venous pressure gradient, plasma LPS concentration and corresponding platelet activation was decreased in cirrhotic portal hypertension after TIPS procedure, and with TSP-1 reduction and VEGF elevation it is possible to reduce the liver function injury caused by portal venous shunt.

Differential Impact of Urban vs. Rural Diets on Gut Microbiome Composition and Circulating Endotoxin in Mourning Doves

Human and rodent studies suggest a Western diet (high in refined carbohydrates, saturated fats, and salt) promotes gut dysbiosis that arises from changes in the resident gut microbiome (GM). This dietary pattern has also been associated with increased circulating concentrations of the endotoxin and immunostimulant, lipopolysaccharide (LPS), which is mediated, in part, through alterations in the GM. In relation, urbanization influences food quality and availability for many wild species which may promote a shift in the GM that could ultimately impact host physiology. As a heavily affected class it is currently unknown how the avian GM is affected following consumption of this dietary model. Therefore, we investigated the potential differential effects of an urban vs. rural dietary intervention on the GM and circulating LPS in Mourning doves (Zenaida macroura). Specifically, adult animals were brought into captivity from a wild population on the Arizona State University campus (Tempe, Arizona; 33° 25′ 11.5” N - 111° 55′ 55.6” W; altitude: 365 m.a.s.l.) and fed either a seed-based diet (rural; n = 6) or urbanized diet (urban; n = 7) over 4-weeks. The urban diet consisted of a mixture of seed and French fries (a food source readily available to birds in urban environments). We hypothesized that the urban diet would differently impact the GM community and increase plasma LPS compared to animals fed a rural diet. After the 4-week intervention, there were no differences in alpha diversity (Shannon index, Pielou's e, Faith's PD; P's ≥ 0.33) or beta diversity (Bray-Curtis, weighted and unweighted UniFrac; P's ≥ 0.35) between groups. However, linear discriminant analysis (LDA) of effect sizes revealed significant differences between the two diets, with rural-fed birds showing increased Chloroflexi (Chloroflexi and Anaerolineae) and Cyanobacteria (Phormidiaceae, Oscillatoriales, Oscillatoriophycideae, Phormidium) (LDA scores ~ 6.0). Moreover, and contrary to our hypothesis, plasma LPS concentrations were significantly higher in the rural group (51.01 ± 1.18 ng/L vs. 45.11 ± 1.02 ng/L, P = 0.003). Notably, birds are transporters of Cyanobacteria which often reside in bodies of water. The LPS molecules in Cyanobacteria also seem to provide protection from antimicrobial compounds which could be beneficial for these animals by promoting the proliferation of commensal microbes. Interesting to note that the lipid A portion of Cyanobacterial LPS is structurally similar to a well-known toll-like receptor 4 (TLR4) antagonist called lipid IVa and is less toxic than other gram-negative-derived LPS. It may be that higher LPS in the seed diet animals could be similarly protective against the TLR4 pathway as they had significantly higher abundance of Cyanobacteria. Future work should look at inflammatory markers downstream of LPS activation to confirm if these diets differ in relation to host health. In conclusion, the urban diet did not support the proliferation of several beneficial microbes that release protective endotoxins, which may have important physiological relevance for birds living in urban environments.

Disruption of intestinal barrier and endotoxemia after traumatic brain injury: Implications for post-traumatic epilepsy.

Traumatic brain injury (TBI) may lead to the disruption of the intestinal barrier (IB), and to the escape of products of commensal gut bacteria, including lipopolysaccharide (LPS), into the bloodstream. We examined whether lateral fluid percussion injury (LFPI) and post-traumatic epilepsy (PTE) are associated with the increased intestinal permeability and endotoxemia, and whether these events in turn are associated with PTE. LFPI was delivered to adult male Sprague-Dawley rats. Before, 1 week, and 7 months after LFPI, the IB permeability was examined by measuring plasma concentration of fluorescein isothiocyanate-labeled dextran (FD4) upon its enteral administration. Plasma LPS concentration was measured in the same animals, using enzyme-linked immunosorbent assay. PTE was examined 7 months after LFPI, with use of video-EEG (electroencephalography) monitoring. One week after LFPI, the IB disruption was detected in 14 of 17 and endotoxemia - in 10 of 17 rats, with a strong positive correlation between FD4 and LPS levels, and between plasma levels of each of the analytes and the severity of neuromotor deficit. Seven months after LFPI, IB disruption was detected in 13 of 15 and endotoxemia in 8 of 15 rats, with a strong positive correlation between plasma levels of the two analytes. Five of 15 LFPI rats developed PTE. Plasma levels of both FD4 and LPS were significantly higher in animals with PTE than among the animals without PTE. The analysis of seven rats, which were examined repeatedly at 1 week and at 7 months, confirmed that late IB disruption and endotoxemia were not due to lingering of impairments occurring shortly after LFPI. LFPI leads to early and remote disruption of IB and a secondary endotoxemia. Early and late perturbations may occur in different subjects. Early changes reflect the severity of acute post-traumatic motor dysfunction, whereas late changes are associated with PTE.

Blueberry and cranberry anthocyanin extracts reduce bodyweight and modulate gut microbiota in C57BL/6J mice fed with a high-fat diet.

Blueberry and cranberry are rich in anthocyanins. The present study was to investigate the effects of anthocyanin extracts from blueberry and cranberry on body weight and gut microbiota. C57BL/6J Mice were divided into six groups (n = 9 each) fed one of six diets namely low-fat diet (LFD), high-fat diet (HFD), HFD with the addition of 1% blueberry extract (BL), 2% blueberry extract (BH), 1% cranberry extract (CL), and 2% cranberry extract (CH), respectively. Feeding BL and BH diets significantly decreased body weight gain by 20-23%, total adipose tissue weight by 18-20%, and total liver lipids by 16-18% compared with feeding HFD. Feeding CH diet but not CL diet reduced the body weight by 27%, accompanied by a significant reduction of total plasma cholesterol by 25% and tumor necrosis factor alpha(TNF-α) by 38%. The metagenomic analysis showed that the supplementation of blueberry and cranberry anthocyanin extracts reduced plasma lipopolysaccharide concentration, accompanied by a reduction in the relative abundance of Rikenella and Rikenellaceae. Dietary supplementation of berry anthocyanin extracts promoted the growth of Lachnoclostridium, Roseburia, and Clostridium_innocuum_group in genus level, leading to a greater production of fecal short-chain fatty acids (SCFA). It was concluded that both berry anthocyanins could manage the body weight and favorably modulate the gut microbiota at least in mice.

LDL apheresis as an alternate method for plasma LPS purification in healthy volunteers and dyslipidemic and septic patients

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. An extracorporeal removal method by polymyxin (PMX) B direct hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including LDLs. Lipoproteins are critical for physiological LPS clearance, as LPSs are carried by LDLs to the liver for elimination. We hypothesized that LDL apheresis could be an alternate method for LPS removal. First, we demonstrated in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in PBS. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL apheresis for familial hypercholesterolemia is also removed during their LDL apheresis sessions, with both electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.

Maintaining intestinal structural integrity is a potential protective mechanism against inflammation in goose fatty liver

Overfeeding causes severe steatosis but not inflammation in goose liver, suggesting existence of protective components. Previous studies have shown that some intestinal microbes and their metabolites damage intestinal structural integrity and function, thus causing inflammation in the development of human and mouse nonalcoholic fatty liver disease. Therefore, this study hypothesizes that intestinal structural integrity of goose is maintained during overfeeding, which may provide goose fatty liver a protective mechanism against inflammation. To test this hypothesis, 48 seventy-day-old healthy Landes male geese were overfed (as overfeeding group) or normally fed (as control group). Blood and intestine (jejunum, ileum, and cecum) samples were harvested on the 12th and 24th d of overfeeding. Data showed that goose fatty liver was successfully induced by 24 d of overfeeding. Hematoxylin-eosin staining analysis indicated that the arrangement of villi and crypts in the intestine was orderly, and the intestinal structure was intact with no pathological symptoms in the 2 groups. Enzyme-linked immunosorbent assay and quantitative PCR analysis indicated no significant differences in the expression of tight junction and inflammation-related genes as well as plasma lipopolysaccharide concentration between the groups. Ileal hypertrophy and cecal atrophy were observed in the overfed vs. control geese, probably because of change of sphingolipid metabolism. Activation of apoptotic pathway may help cecum avoid necrosis-induced inflammation. In conclusion, healthy and intact intestine provides a layer of protection for goose fatty liver against inflammation. Sphingolipid metabolism may be involved in the adaptation of ileum and cecum to overfeeding. The hypertrophy of ileum makes it an important contributor to the development of goose fatty liver. The atrophy and decline in the function of cecum may be caused by apoptosis induced by overfeeding.

Gut Microbiota Dysbiosis and Increased Plasma LPS and TMAO Levels in Patients With Preeclampsia.

Objective: To characterize the gut microbiota in patients with preeclampsia (PE) compared with healthy controls.Methods: We analyzed and compared the microbiota communities in the feces of 48 PE patients with 48 age-, gestational weeks-, and pre-pregnancy body mass index-matched healthy controls using 16S rRNA gene sequencing, and also we tested fecal and plasma lipopolysaccharide (LPS) and plasma trimethylamine-N-oxide (TMAO) concentration levels in the two groups.Results: Compared with the control group, microbial alpha diversity was lower in the PE group, but there was no statistically significant difference between the two groups. At the phylum level, Firmicutes (51.64% PE vs. 59.62% Control, P < 0.05), Bacteroidetes (40.51% PE vs. 34.81% Control, P< 0.05), Proteobacteria (4.51% PE vs. 2.56% Control, P < 0.05), and Actinobacteria (2.90% PE vs. 1.77% Control, P < 0.05), exhibited significant differences between the PE group and the control group. LEfSe analysis found 17 differentially abundant taxa between the two groups. PICRUSt analysis found that in the KEGG pathways, the microbial gene functions related to LPS biosynthesis were higher in the fecal microbiome of the PE group. The fecal and plasma LPS concentrations and plasma TMAO concentrations of PE patients were higher than those of the healthy controls.Conclusion: PE patients had gut microbiota dysbiosis and increased plasma LPS and TMAO levels, which will lead to a better understanding of the relationship between the gut microbiota and PE.

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients.

The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage. Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry. 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103ng/mL, P=0.005). Patients with severe acute alcoholic hepatitis (n=16; 113 vs 74ng/mL, P=0.012), diabetic patients (n=22; 99 vs 70ng/mL, P=0.028) and those not receiving beta blockers (n=44; 98 vs 72ng/mL, P=0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n=7; 144 vs 76ng/mL, P=0.45) or SIRS (n=10; 106 vs 75ng/mL, P=0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR=4.39; 95%CI=1.79-10.76) or MELD (OR=8.24; 95%CI=3.19-21.32) scores. Patients dying from liver insufficiency (n=6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75ng/mL, P=0.089). In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.

Oligofructose decreases serum lipopolysaccharide and plasminogen activator inhibitor‐1 in adults with overweight/obesity

To determine the effect of prebiotic supplementation on metabolic endotoxemia and systemic inflammation in adults with overweight and obesity. Samples from a previously conducted randomized, double-blind, placebo-controlled trial were used for analysis. Participants were randomized to 21 g of oligofructose (n = 20; BMI 30.4 kg/m2 ) or a maltodextrin placebo (n = 17; BMI 29.5 kg/m2 ) for 12 weeks. A total of 37 participants had samples available for the current analysis. Resistin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage chemoattractant protein-1 (MCP-1) were quantified using MILLIPLEX® assays. Lipopolysaccharide (LPS) was measured using PyroGene™ Recombinant Factor C Assay. Plasma LPS concentrations were reduced by 40% in the oligofructose group over 12 weeks compared to a 48% increase in the placebo group (P = 0.04). PAI-1, a risk factor for thrombosis, was reduced to a greater extent in the oligofructose group (-17.3 ± 2.6 ng/ml) compared to the placebo group (-9.7 ± 1.8 ng/ml; P = 0.03). Oligofructose did not affect IL-6, TNF-α, MCP-1, adiponectin, or resistin. Oligofructose reduces metabolic endotoxemia and PAI-1. Incorporating prebiotics into the diet through supplements or functional foods may help mitigate some markers of obesity-associated inflammation.

Impact of metritis on the generation of reactive oxygen species by circulating phagocytes and plasma lipopolysaccharide concentration in peripartum dairy cows.

This study examined the relationship between postpartum metritis, reactive oxygen species (ROS) generation, and plasma lipopolysaccharide (LPS) concentration in peripartum dairy cows. Blood was collected twice weekly from 2 weeks prepartum through 6 weeks postpartum. Whole blood chemiluminescence (WBCL) was measured using the luminol-enhanced zymosan-stimulated chemiluminescence assay. Cows were examined for uterine health disorders and classified into two groups, healthy (n = 11) and metritis (n = 5). Metritis had a significant effect on WBCL, with cows with metritis having a higher WBCL. Plasma LPS concentrations in cows with metritis were significantly higher than in healthy cows. To examine the effect of LPS on WBCL, blood was sampled in healthy peripartum cows (1 to 2 weeks prepartum, n = 8; 0 to 3 weeks postpartum, n = 11; and 4 to 8 weeks postpartum, n = 8) and incubated with LPS. At 1 endotoxin units/mL of LPS, similar to the plasma LPS concentration in cows with metritis, the WBCL increased in cows at 0 to 3 weeks postpartum. Results indicate that the increase in ROS generation and plasma LPS concentration are associated with metritis, and LPS may be responsible for enhanced ROS generation in early postpartum dairy cows.

Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa.

Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital. This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint. Of 99 patients (median CD4 count 72 cells/mm³), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002). Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute.

Endogenous LPS Alters Liver GH/IGF System Gene Expression and Plasma Lipoprotein Lipase in Goats

Endotoxin lipopolysaccharide (LPS) affects the ruminant health and animal performance. The main purposes of this study were to investigate the potential effects of GH/IGF system and lipoprotein lipase (LPL) concentration on resistance the circulating LPS concentration increased in liver with high concentrate diet treatment. Non-lactating goats were randomly allocated to two groups: a high-concentrate diet (HCD) or a low-concentrate diet (LCD) in cross over design and the blood collection at different time points after feeding at the end of the experiment. The average rumen pH was significantly reduced (P<0.05), but the duration with pH was not more than 120 min in the HCD group. The plasma LPL concentration was significantly raised (P<0.05). However, from 2 h onwards, LPS concentration was significantly reduced (P<0.01) in the HCD group compared with LCD group. In addition, the plasma IGF1 concentration and the hepatic insulin-like growth factor-1 receptor (IGF1R) mRNA expression were markedly reduced (P<0.05). However, growth hormone (GH) secretion at 15, 30, and 45 min after feeding and growth hormone receptor (GHR) mRNA expression in the liver was significantly increased (P<0.05) in HCD group. The correlation analysis showed that the plasma LPL concentration was positively correlated with hepatic GHR mRNA expression (P<0.05). Conversely, the plasma LPS concentration was negatively correlated with LPL concentration (P<0.05). These findings reveal that alterations in GH/IGF system function in response to a high-concentrate diet are accompanied by corresponding changes in systemic LPL in non-lactating goats' liver in presence of endogenous LPS stress.

Lipopolysaccharide and toll-like receptor 4 in dogs with congenital portosystemic shunts

Surgical attenuation of a congenital portosystemic shunt (CPSS) results in increased portal vein perfusion, liver growth and clinical improvement. Portal lipopolysaccharide (LPS) is implicated in liver regeneration via toll-like receptor (TLR) 4 mediated cytokine activation. The aim of this study was to investigate factors associated with LPS in dogs with CPSS. Plasma LPS concentrations were measured in the peripheral and portal blood using a limulus amoebocyte lysate (LAL) assay.LPS concentration was significantly greater in the portal blood compared to peripheral blood in dogs with CPSS (P = 0.046) and control dogs (P = 0.002). LPS concentrations in the peripheral (P = 0.012) and portal (P = 0.005) blood of dogs with CPSS were significantly greater than those of control dogs. The relative mRNA expression of cytokines and TLRs was measured in liver biopsies from dogs with CPSS using quantitative PCR. TLR4 expression significantly increased following partial CPSS attenuation (P = 0.020). TLR4 expression was significantly greater in dogs that tolerated complete CPSS attenuation (P = 0.011) and those with good portal blood flow on pre-attenuation (P = 0.004) and post-attenuation (P = 0.015) portovenography. Serum interleukin (IL)-6 concentration was measured using a canine specific ELISA and significantly increased 24 h following CPSS attenuation (P < 0.001). Portal LPS was increased in dogs with CPSS, consistent with decreased hepatic clearance. TLR4 mRNA expression was significantly associated with portal blood flow and increased following surgery. These findings support the concept that portal LPS delivery is important in the hepatic response to surgical attenuation. Serum IL-6 significantly increased following surgery, consistent with LPS stimulation via TLR4, although this increase might be non-specific.