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Probiotic Supplementation Has a Limited Effect on Circulating Immune and Inflammatory Markers in Healthy Adults: A Systematic Review of Randomized Controlled Trials.
Mohr, AE, Basile, AJ, Crawford, MS, Sweazea, KL, Carpenter, KC
Journal of the Academy of Nutrition and Dietetics. 2020;(4):548-564
Abstract
BACKGROUND A main mechanism of action proposed for oral probiotic supplementation is immunomodulation, which is expected to impart health benefits in the host by influencing circulating immune and inflammatory factors. To date, the effectiveness of probiotic supplementation for immunomodulation in healthy adults without disease has not been evaluated in a systematic review. OBJECTIVE The objective of this systematic review was to evaluate the effect of probiotic supplementation on circulating immune and inflammatory markers of healthy adults compared to placebo. METHODS PubMed, SCOPUS, ISI Web of Science, ProQuest, and Cochrane databases were searched for English articles up to May 15, 2019. Additional papers were identified by checking references of relevant papers. Only randomized controlled trials studying the administration of probiotic supplements compared to placebo on immune and inflammatory markers in healthy adults (aged 18 to 65 years), without acute or chronic disease, and in generally good health were examined. Independent extraction of articles was conducted by two authors using predefined search terms and restrictions/filters. The methodologic quality of each study was appraised using the Academy of Nutrition and Dietetics Evidence Analysis Library Quality Rating Worksheet and the body of evidence was assessed using the Academy of Nutrition and Dietetics Grade Definitions and Conclusion Grading Table. RESULTS Eighteen articles, including 819 subjects, met eligibility criteria and were included in the present systematic review. Five articles were rated neutral in quality and 13 were rated high in quality. Eight articles reported a significant effect on immune and/or inflammatory parameters including increases in natural killer cells, lymphocytes, and monocytes, and decreases in proinflammatory cytokine concentrations. CONCLUSIONS Based on the 18 articles extracted in this systemic review, probiotic supplementation was concluded to have a limited effect on immune and inflammatory markers in healthy adults. Overall, the evidence was heterogenous, precluding a meta-analysis, and difficult to aggregate and conclude on effect size. SYSTEMATIC REVIEW REGISTRATION NUMBER PROSPERO ref CRD42018110856.
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Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.
Ter Horst, R, van den Munckhof, ICL, Schraa, K, Aguirre-Gamboa, R, Jaeger, M, Smeekens, SP, Brand, T, Lemmers, H, Dijkstra, H, Galesloot, TE, et al
Arteriosclerosis, thrombosis, and vascular biology. 2020;(7):1787-1800
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Abstract
OBJECTIVE Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.
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Vegetarian-Based Dietary Patterns and their Relation with Inflammatory and Immune Biomarkers: A Systematic Review and Meta-Analysis.
Craddock, JC, Neale, EP, Peoples, GE, Probst, YC
Advances in nutrition (Bethesda, Md.). 2019;(3):433-451
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Abstract
Dietary patterns with substantial proportions of energy from plant sources have been associated with favorable biomarkers of low-grade inflammation. Less is known of the relation between vegetarian-based dietary patterns and markers of inflammation and immune status. This systematic review and meta-analysis aimed to determine the relation between vegetarian-based dietary patterns and inflammatory and immune markers (C-reactive protein, tumour necrosis factor α, fibrinogen, natural killer cells, leukocytes, lymphocytes, thrombocytes, interleukins, and immunoglobulins). PubMed, Medline, and Cochrane scientific databases were searched to identify relevant studies. Random effects meta-analyses were conducted to assess the weighted mean differences (WMDs) for each outcome variable between vegetarian and non-vegetarian groups. Thirty observational and 10 intervention studies were included in the review. Pooled effects of vegetarian-based dietary patterns were associated with significantly lower concentrations of CRP (WMD: -0.61 mg/L; 95% CI: -0.91, -0.32 mg/L; P = 0.0001), fibrinogen (WMD: -0.22 g/L; 95% CI: -0.41, -0.04 mg/L; P = 0.02), and total leukocyte (WMD: -0.62 × 10(3)/μL; 95% CI -1.13 × 10(3), -0.10 × 10(3)/μL; P = 0.02) compared with those following non-vegetarian dietary patterns in observational studies. Insufficient data were identified for a meta-analysis of intervention studies. This study provides evidence that vegetarian-based dietary patterns are associated with lowered serum C-reactive protein, fibrinogen, and total leukocyte concentrations. Future research should focus on large-scale intervention trials, contrasting differences in inflammation and immune status and function between vegetarian and non-vegetarian-based populations.
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Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Ladva, CN, Golan, R, Liang, D, Greenwald, R, Walker, DI, Uppal, K, Raysoni, AU, Tran, V, Yu, T, Flanders, WD, et al
PloS one. 2018;(9):e0203468
Abstract
INTRODUCTION Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
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Isolated vitamin D supplementation improves the immune-inflammatory biomarkers in younger postmenopausal women: a randomized, double-blind, placebo-controlled trial.
Bueloni-Dias, FN, Orsatti, CL, Cangussu, LM, Poloni, PF, Spadoto-Dias, D, Nahas-Neto, J, Nahas, EAP
Menopause (New York, N.Y.). 2018;(8):897-903
Abstract
OBJECTIVE The aim of this study was to evaluate the effect of vitamin D (VitD) supplementation on immune-inflammatory biomarkers in younger postmenopausal women. METHODS In this double-blind, placebo-controlled trial, 160 postmenopausal women aged 50 to 65 years with amenorrhea ≥12 months were randomized into two groups: VitD group, oral supplementation with 1000 IU VitD3/day (n = 80) or placebo group (n = 80). The intervention time was 9 months, and the women were assessed at baseline and endpoint. Serum levels of interleukins (ILs)-1β, IL-5, IL-6, IL-10, IL-12ρ70, IL-17α, tumor necrosis factor-alpha, and interferon-gamma were determined by immunoassay. Plasma concentrations of 25-hydroxyvitamin D [25(OH)D] were measured by high-performance liquid chromatography. Per-protocol analysis was adopted as the statistical method using a gamma distribution and repeated measures design, followed by Wald's multiple comparisons test. RESULTS The two groups were similar at baseline in terms of clinical and laboratory parameters. After 9 months, there was a significant increase of 25(OH)D levels in the VitD group (+45.4%, P < 0.001) and a decrease (-18.5%, P = 0.049) in the placebo group. A significant decrease in IL-5, IL-12p70, IL-17α, tumor necrosis factor-alpha, and interferon-gamma levels was observed in the VitD group (P < 0.05). IL-5 and IL-6 levels were significantly lower in the VitD group compared to the placebo group (P < 0.05). There were no significant intervention effects on serum IL-1β or IL-10 levels in either group (P > 0.05). CONCLUSIONS In younger postmenopausal women, isolated supplementation with 1000 IU of VitD3 for 9 months was associated with a reduction in proinflammatory biomarkers.
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25-hydroxyvitamin D correlates with inflammatory markers in cord blood of healthy newborns.
Rosendahl, J, Holmlund-Suila, E, Helve, O, Viljakainen, H, Hauta-Alus, H, Valkama, S, Enlund-Cerullo, M, Hytinantti, T, Tervahartiala, T, Sorsa, T, et al
Pediatric research. 2017;(5):731-735
Abstract
BACKGROUND Vitamin D is a potent immunomodulator and may play a role in the development of the fetal innate immune functions. The aim of our study was to evaluate inflammatory markers in cord blood of healthy newborns in relation to vitamin D status at birth. METHODS We studied the concentrations of inflammatory markers, matrix metalloproteinase 8 (MMP-8) and high sensitivity CRP (hs-CRP), and 25-hydroxyvitamin D (25(OH)D) in cord blood of 939 healthy term infants born to mothers of Caucasian origin. We evaluated perinatal factors that affect the concentrations of MMP-8 and hs-CRP, and further explored associations between cord blood 25(OH)D and these inflammatory biomarkers. RESULTS Majority (99%) of the cohort was vitamin D sufficient (>50 nmol/l or 20 ng/ml). We observed a positive correlation between cord blood 25(OH)D and MMP-8 concentrations, and between 25(OH)D and hs-CRP concentrations. After adjustment for potential confounders (parity, antenatal antibiotic treatment, gestational age, mode of delivery, and maternal prepregnancy BMI), the association of 25(OH)D with MMP-8 and hs-CRP remained significant. CONCLUSION Cord blood 25(OH)D correlates with inflammatory markers MMP-8 and hs-CRP. The findings may reflect the diverse immunomodulatory functions of vitamin D in the innate immune response of the newborn.
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Inflammatory gene expression in whole blood cells after EPA vs. DHA supplementation: Results from the ComparED study.
Vors, C, Allaire, J, Marin, J, Lépine, MC, Charest, A, Tchernof, A, Couture, P, Lamarche, B
Atherosclerosis. 2017;:116-122
Abstract
BACKGROUND AND AIMS Whether EPA and DHA exert similar anti-inflammatory effects through modulation of gene expression in immune cells remains unclear. The aim of the study was to compare the impact of EPA and DHA supplementation on inflammatory gene expression in subjects at risk for cardiometabolic diseases. METHODS In this randomized double-blind crossover trial, 154 men and women with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1) EPA (2.7 g/d); 2) DHA (2.7 g/d); 3) corn oil (3 g/d), separated by a 9-wk washout. Pro- and anti-inflammatory gene expression was assessed in whole blood cells by RT-qPCR after each treatment in a representative sample of 44 participants. RESULTS No significant difference was observed between EPA and DHA in the expression of any of the genes investigated. Compared with control, EPA enhanced TRAF3 and PPARA expression and lowered CD14 expression (p < 0.01) whereas DHA increased expression of PPARA and TNFA and decreased CD14 expression (p < 0.05). Variations in gene expression after EPA and after DHA were strongly correlated for PPARA (r = 0.73, p < 0.0001) and TRAF3 (r = 0.66, p < 0.0001) and less for TNFA (r = 0.46, p < 0.005) and CD14 (r = 0.16, p = 0.30). CONCLUSIONS High-dose supplementation with either EPA or DHA has similar effects on the expression of many inflammation-related genes in immune cells of men and women at risk for cardiometabolic diseases. The effects of EPA and of DHA on anti-inflammatory gene expression may be more consistent than their effects on expression of pro-inflammatory genes in whole blood cells.
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Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.
Fonseca, FAH, Izar, MC, Maugeri, IML, Berwanger, O, Damiani, LP, Pinto, IM, Szarf, G, França, CN, Bianco, HT, Moreira, FT, et al
Trials. 2017;(1):601
Abstract
BACKGROUND Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. METHODS/DESIGN BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events. DISCUSSION BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation. TRIAL REGISTRATION ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.
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Impact of Bariatric Surgery on White Adipose Tissue Inflammation.
Labrecque, J, Laforest, S, Michaud, A, Biertho, L, Tchernof, A
Canadian journal of diabetes. 2017;(4):407-417
Abstract
Excess fat mass accumulation can lead to a wide range of metabolic and cardiovascular complications resulting from dysfunctional adipose tissue (AT). The latter includes immune cell infiltration and altered secretion of anti- and proinflammatory mediators, which contribute to systemic, low-grade inflammation. In this article, we review available literature documenting the impact of surgery-induced weight loss on macrophage infiltration and tissue expression or circulating levels of a broad spectrum of inflammatory mediators. Reports generally show that bariatric surgery may reverse both macrophage infiltration and the altered secretory profile observed in the AT of patients with severe obesity. However, further studies are needed to confirm or elucidate the effects of specific bariatric surgery procedures on white AT inflammation and to shed light on the mechanisms involved in these effects.
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Modulation of inflammatory response arising from high-intensity intermittent and concurrent strength training in physically active males.
Monteiro, PA, Campos, EZ, de Oliveira, FP, Peres, FP, Rosa-Neto, JC, Pimentel, GD, Lira, FS
Cytokine. 2017;:104-109
Abstract
The purposes of this study were to determine: (i) the extent of an acute session of high-intensity intermittent exercise (HIIE) followed by a concurrent strength session (Conc) on the increase of systemic inflammatory cytokines and chemokines, and (ii) whether eight weeks of high intensity interval training plus concurrent strength training alters the acute inflammatory response and immune status. Ten recreationally active males (aged 26.9±4.3years) performed two experimental exercise sessions interspersed by eight weeks of HIIT plus concurrent strength training. The experimental exercise session was composed of a 5-km run on a treadmill (1:1 at 100% of maximal aerobic speed (MAS)), and after 10min of passive recovery, back squat exercises were performed (80% 1RM, four sets until exhaustion). Serum samples were collected after fasting, pre-HIIE, post-HIIE, Pre-Conc, Post-Conc, and 30 and 60min post-exercise session. The comparison between both concurrent exercise sessions was performed using repeated measure ANOVA, with the Bonferroni Post-hoc when necessary. Interleukin-6 (IL-6) presented a moment effect (F=6.72; p<0.05), with Post-Conc significantly higher than pre-HIIE, Post-HIIE, and 60min, only a tendency was found between pre-HIIE and post-HIIE (difference=-5.99; p=0.09). MCP-1 and IL-1ra did not present effects for condition, moment, or interaction. Interleukin-10 (IL-10) presented both moment and interaction effects (F=5.31 and 2.50; p=0.005 and 0.036). Pre-Conc and Post-Conc were significantly higher than Pre-HIIE. The interaction between before and after eight weeks of concurrent training probably occurred at Post-Conc (11.42±3.09pgmL-1 and 8.88±1.29pgmL-1). In addition, maintenance of immune function was observed. Therefore, HIIE and concurrent strength exercise lead to an increase in cytokines response, but eight weeks of training program promoted anti-inflammatory response after an acute session of concurrent exercise.