Immunomodulatory effects of fucoidan in recreationally active adult males undertaking 3-weeks of intensified training.

The aim of the current study was to determine whether daily fucoidan supplementation (Undaria pinnatifida extract containing >85% fucoidan, 1 g/day) for three-weeks in a double blind-placebo controlled cross-over trial (ACTRN12621000872831) could modulate alterations in faecal (calprotectin, lysozyme and IgA) and salivary (lactoferrin, lysozyme and IgA) markers of mucosal immune competence typically observed in response to both acute physical activity, and a period of intensified exercise training, in healthy recreationally active men (n = 12). Participants responded positively to the intensified training with 16-19% improvement in mean power that was not different between supplement groups. Faecal biomarkers and concentrations of lactoferrin, lysozyme and IgA from resting saliva samples were largely stable over the supplementation period. Concentrations of salivary biomarkers varied significantly over time in response to acute exercise, however differences between supplementation groups were modest. For salivary lysozyme, there was a trend for a lower magnitude of increase post-exercise (p = 0.08) and limited return towards pre-exercise in response to fucoidan. For salivary IgA, a greater acute exercise response was noted for IgA in response to fucoidan (~2.7-fold higher; p = 0.02). Different dosage and supplementation protocols and inclusion of additional immune markers should be considered in subsequent assessments of any potential benefits of fucoidan supplementation in healthy active adults.

Blood oxidative stress biomarkers in women: influence of oral contraception, exercise, and N-acetylcysteine.

PURPOSE: To compare physiological responses to submaximal cycling and sprint cycling performance in women using oral contraceptives (WomenOC) and naturally cycling women (WomenNC) and to determine whether N-acetylcysteine (NAC) supplementation mediates these responses. METHODS: Twenty recreationally trained women completed five exercise trials (i.e., an incremental cycling test, a familiarisation trial, a baseline performance trial and two double-blind crossover intervention trials). During the intervention trials participants supplemented with NAC or a placebo 1 h before exercise. Cardiopulmonary parameters and blood biochemistry were assessed during 40 min of fixed-intensity cycling at 105% of gas-exchange threshold and after 1-km cycling time-trial. RESULTS: WomenOC had higher ventilation (ß [95% CI] = 0.07 L·min-1 [0.01, 0.14]), malondialdehydes (ß = 12.00 mmol·L-1 [6.82, 17.17]) and C-reactive protein (1.53 mg·L-1 [0.76, 2.30]), whereas glutathione peroxidase was lower (ß =  22.62 mU·mL-1 [- 41.32, - 3.91]) compared to WomenNC during fixed-intensity cycling. Plasma thiols were higher at all timepoints after NAC ingestion compared to placebo, irrespective of group (all p < 0.001; d = 1.45 to 2.34). For WomenNC but not WomenOC, the exercise-induced increase in malondialdehyde observed in the placebo trial was blunted after NAC ingestion, with lower values at 40 min (p = 0.018; d = 0.73). NAC did not affect cycling time-trial performance. CONCLUSIONS: Blood biomarkers relating to oxidative stress and inflammation are elevated in WomenOC during exercise. There may be an increased strain on the endogenous antioxidant system during exercise, since NAC supplementation in WomenOC did not dampen the exercise-induced increase in malondialdehyde. Future investigations should explore the impact of elevated oxidative stress on exercise adaptations or recovery from exercise in WomenOC.

The Gut Microbiome of Adults with Allergic Rhinitis Is Characterised by Reduced Diversity and an Altered Abundance of Key Microbial Taxa Compared to Controls.

INTRODUCTION: Unique gut microbial colonisation patterns are associated with the onset of allergic disease in infants; however, there is insufficient evidence to determine if aberrant microbial composition patterns persist in adult allergic rhinitis (AR) sufferers. OBJECTIVE: To compare the gut microbiome composition between adult AR sufferers and controls. METHODS: Gut microbial composition in stool samples was compared between 57 adult AR sufferers (39.06 ± 13.29 years) and 23 controls (CG; 36.55 ± 10.51 years) via next-generation sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Taxonomic classification and identity assignment was performed using a reference-based approach with the NCBI database of 16S rRNA gene sequences. RESULTS: Species richness determined via the Shannon index was significantly reduced in the AR cohort compared to the CG (4.35 ± 0.59 in AR vs. 4.65 ± 0.55 in CG, p = 0.037); trends for reductions in operational taxonomic unit (OTU) counts, inverse Simpson, and CHAO1 diversity indices were also noted. Bacteroidetes (p = 0.014) was significantly more abundant in the AR group than in the CG. In contrast, the Firmicutes phylum was significantly less abundant in the AR group than in the CG (p = 0.006). An increased abundance of Parabacteroides (p = 0.008) and a reduced abundance of Oxalobacter (p = 0.001) and Clostridiales (p = 0.005) were also observed in the AR cohort compared to the CG. CONCLUSION: Adult AR sufferers have a distinct gut microbiome profile, marked by a reduced microbial diversity and altered abundance of certain microbes compared to controls. The results of this study provide evidence that unique gut microbial patterns occur in AR sufferers in adulthood and warrant further examination in the form of mechanistic studies.

Trimethylamine N-oxide: heart of the microbiota-CVD nexus?

We critically review potential involvement of trimethylamine N-oxide (TMAO) as a link between diet, the gut microbiota and CVD. Generated primarily from dietary choline and carnitine by gut bacteria and hepatic flavin-containing mono-oxygenase (FMO) activity, TMAO could promote cardiometabolic disease when chronically elevated. However, control of circulating TMAO is poorly understood, and diet, age, body mass, sex hormones, renal clearance, FMO3 expression and genetic background may explain as little as 25 % of TMAO variance. The basis of elevations with obesity, diabetes, atherosclerosis or CHD is similarly ill-defined, although gut microbiota profiles/remodelling appear critical. Elevated TMAO could promote CVD via inflammation, oxidative stress, scavenger receptor up-regulation, reverse cholesterol transport (RCT) inhibition, and cardiovascular dysfunction. However, concentrations influencing inflammation, scavenger receptors and RCT (≥100 µm) are only achieved in advanced heart failure or chronic kidney disease (CKD), and greatly exceed pathogenicity of <1-5 µm levels implied in some TMAO-CVD associations. There is also evidence that CVD risk is insensitive to TMAO variance beyond these levels in omnivores and vegetarians, and that major TMAO sources are cardioprotective. Assessing available evidence suggests that modest elevations in TMAO (≤10 µm) are a non-pathogenic consequence of diverse risk factors (ageing, obesity, dyslipidaemia, insulin resistance/diabetes, renal dysfunction), indirectly reflecting CVD risk without participating mechanistically. Nonetheless, TMAO may surpass a pathogenic threshold as a consequence of CVD/CKD, secondarily promoting disease progression. TMAO might thus reflect early CVD risk while providing a prognostic biomarker or secondary target in established disease, although mechanistic contributions to CVD await confirmation.

Temporal changes in blood oxidative stress biomarkers across the menstrual cycle and with oral contraceptive use in active women.

PURPOSE: To examine the temporal changes in blood oxidative stress biomarkers in recreationally-trained women that were naturally-cycling (WomenNC) or using oral contraceptives (WomenOC) across one month. METHODS: Blood samples were acquired at three timepoints of the menstrual cycle (1: early-follicular, 2: late-follicular and 3: mid-luteal) and oral contraceptive packet (1: InactiveOC, 2: Mid-activeOC and 3: Late-activeOC) for determination of estradiol, progesterone, oxidative stress, C-reactive protein (CRP) and other cardiometabolic biomarkers in plasma and serum. RESULTS: There was a Group by Time effect on estradiol (p < 0.001, partial η2 = 0.64) and progesterone (p < 0.001, partial η2 = 0.77). Malondialdehyde, lipid hydroperoxides and CRP concentrations were higher in WomenOC during Late-activeOC compared to InactiveOC (+ 96%, + 23% and + 104%, respectively, p < 0.05). However, there were no changes in these biomarkers across the menstrual cycle in WomenNC (p > 0.05). At all timepoints (i.e., 1, 2 and 3), WomenOC had elevated lipid hydroperoxides (+ 28, + 48% and + 50%) and CRP (+ 71%, + 117% and + 130%) compared to WomenNC (p < 0.05, partial η2 > 0.25). There was no Group by Time effect on non-enzymatic antioxidants or glutathione peroxidase; however, glutathione peroxidase was lower in WomenOC, i.e., main effect of group (p < 0.05, partial η2 > 0.20). CONCLUSION: These findings demonstrate that WomenOC not only have higher oxidative stress and CRP than WomenNC, but also a transient increase across one month of habitual oral contraceptive use. Since changes in oxidative stress and CRP often relate to training stress and recovery, these outcomes may have implications to workload monitoring practices in female athletes.

Reliability of a point-of-care device to determine oxidative stress in whole blood before and after acute exercise: A practical approach for the applied sports sciences.

Measuring alterations in redox homoeostasis in athletes can provide insights into their responses to training such as adaptations or fatigued states. However, redox monitoring is impractical in athletes given the time burden of venepuncture and subsequent laboratory assays. The ability of point-of-care tests (POC): 1) Free Oxygen Radical Test (FORT) and 2) Free Oxygen Radical Defence (FORD), to reliably measure whole blood oxidative stress between days and after exercise is unknown as well as their relationship with laboratory measures (F2-isoprostanes, total antioxidant capacity; TAC). Participants completed two trials performed on separate days comprising blood sampling at rest (n=22) and after treadmill-running (n=14). Between-day CVs for FORT (4.6%) and FORD (4.8%) were acceptable at rest. There was no difference in the between-day magnitude of change in any biomarker from pre- to post-exercise (p>0.05), yet the within-trial change in FORD was variable (trial one: +4.5%, p=0.15; trial two: +6.3%, p<0.05). TAC and FORD were significantly correlated pre- and post-exercise (r=~0.53, p<0.05), whereas F2-isoprostanes and FORT had a significant correlation pre-exercise only (r=0.45, p=0.03). Overall, the POC tests are reliable and could be used for baseline longitudinal redox monitoring. More data is required on POC tests for assessing redox perturbations induced by exercise.

Key viral immune genes and pathways identify elite athletes with URS.

PURPOSE: Habitual intense exercise may increase the incidence of upper respiratory symptoms (URS) in elite athletes. This study investigated whether immune gene expression could identify gene markers that discriminate athletes with a higher prevalence of URS. METHODS: This cross-sectional analysis of elite Australian athletes from various sports investigated whether athletes retrospectively reporting URS for two days or more in a month (n=38), had an altered immune gene expression profile compared with asymptomatic athletes (n=33). Peripheral blood samples were collected during Olympic selection events with corresponding URS data collected for the one-month period before sampling. Digital immune gene expression analysis was undertaken using the NanoString PanCancer Immune Profiling panel. RESULTS: Fifty immune genes were differentially expressed between the groups (p<0.05) and approximately 78% of these genes were more highly expressed in athletes reporting URS. Many of these genes were interferon-stimulated genes or genes involved in the Jak/Stat signalling pathway. Only interferon alpha inducible protein 27 (IFI27), an interferon stimulated gene involved in viral response, remained significantly higher in athletes reporting URS (log2 fold-difference=2.49, odds ratio 1.02 per unit increase; p<0.01) post-adjustment and discriminated athletes reporting URS from asymptomatic athletes with 78% accuracy. CONCLUSIONS: Expression of IFI27 could differentiate athletes reporting URS from asymptomatic athletes, a gene that is upregulated in the immune response to viral infection. Upregulation of viral signalling pathways provides novel information on the potential aetiology of URS in elite Olympic athletes.

Fucoidan Supplementation Restores Fecal Lysozyme Concentrations in High-Performance Athletes: A Pilot Study.

Nutritional strategies to help promote immune competence are of particular interest for a range of population groups. This study aimed to assess the potential impacts of fucoidan, a seaweed-derived bioactive polysaccharide, on gut markers of immunity and inflammation. A group of professional team-sport athletes were selected for inclusion in the study given the recognized potential for intense physical activity to induce alterations in immune function. A retrospective analysis was performed on stored fecal samples which had been collected from professional team-sport athletes (n = 22) and healthy adults (n = 11) before and after seven days of supplementation with fucoidan (Fucus vesiculosus/Undaria pinnatifida extract, 1 g/d). Fecal concentrations of calprotectin, secretory immunoglobulin A (sIgA) and lysozyme were determined using enzyme-linked immunosorbent assays. The supplement was well tolerated by participants with no adverse events reported. At baseline, fecal lysozyme concentrations were ~73% higher in the healthy adults compared to the professional athletes (p = 0.001). For the professional athletes, a significant (~45%) increase in fecal lysozyme was observed following the supplementation period (p = 0.001). These data suggest that fucoidan supplementation may have the potential to promote the secretion of antimicrobial peptides in specific population groups and contribute to the regulation of mucosal immune health.

A correlation-based network for biomarker discovery in obesity with metabolic syndrome.

BACKGROUND: Obesity is associated with chronic activation of the immune system and an altered gut microbiome, leading to increased risk of chronic disease development. As yet, no biomarker profile has been found to distinguish individuals at greater risk of obesity-related disease. The aim of this study was to explore a correlation-based network approach to identify existing patterns of immune-microbiome interactions in obesity. RESULTS: The current study performed correlation-based network analysis on five different datasets obtained from 11 obese with metabolic syndrome (MetS) and 12 healthy weight men. These datasets included: anthropometric measures, metabolic measures, immune cell abundance, serum cytokine concentration, and gut microbial composition. The obese with MetS group had a denser network (total number of edges, n = 369) compared to the healthy network (n = 299). Within the obese with MetS network, biomarkers from the immune cell abundance group was found to be correlated to biomarkers from all four other datasets. Conversely in the healthy network, immune cell abundance was only correlated with serum cytokine concentration and gut microbial composition. These observations suggest high involvement of immune cells in obese with MetS individuals. There were also three key hubs found among immune cells in the obese with MetS networks involving regulatory T cells, neutrophil and cytotoxic cell abundance. No hubs were present in the healthy network. CONCLUSION: These results suggest a more complex interaction of inflammatory markers in obesity, with high connectivity of immune cells in the obese with MetS network compared to the healthy network. Three key hubs were identified in the obese with MetS network, involving Treg, neutrophils and cytotoxic cell abundance. Compared to a t-test, the network approach offered more meaningful results when comparing obese with MetS and healthy weight individuals, demonstrating its superiority in exploratory analysis.

Selection of microbial biomarkers with genetic algorithm and principal component analysis.

BACKGROUND: Principal components analysis (PCA) is often used to find characteristic patterns associated with certain diseases by reducing variable numbers before a predictive model is built, particularly when some variables are correlated. Usually, the first two or three components from PCA are used to determine whether individuals can be clustered into two classification groups based on pre-determined criteria: control and disease group. However, a combination of other components may exist which better distinguish diseased individuals from healthy controls. Genetic algorithms (GAs) can be useful and efficient for searching the best combination of variables to build a prediction model. This study aimed to develop a prediction model that combines PCA and a genetic algorithm (GA) for identifying sets of bacterial species associated with obesity and metabolic syndrome (Mets). RESULTS: The prediction models built using the combination of principal components (PCs) selected by GA were compared to the models built using the top PCs that explained the most variance in the sample and to models built with selected original variables. The advantages of combining PCA with GA were demonstrated. CONCLUSIONS: The proposed algorithm overcomes the limitation of PCA for data analysis. It offers a new way to build prediction models that may improve the prediction accuracy. The variables included in the PCs that were selected by GA can be combined with flexibility for potential clinical applications. The algorithm can be useful for many biological studies where high dimensional data are collected with highly correlated variables.

Recovery of Lactobacillus casei strain Shirota (LcS) from faeces with 14 days of fermented milk supplementation in healthy Australian adults.

BACKGROUND AND OBJECTIVES: A key measure for classifying bacteria as a probiotic is the ability to survive gastric transport and be recoverable in faeces. The aim of this study was to determine whether Lactobacillus casei strain Shirota (LcS) could be recovered in the faeces of healthy young Australian adults following ingestion of a fermented milk drink. METHODS AND STUDY DESIGN: A cohort of 25 healthy individuals (male/female: 14/11; age: 29.3±6.6 years; BMI: 25.3±2.7 kg/m2, mean±SD) ingested one 65 ml bottle of fermented milk containing 6.5×109 LcS live cells daily for 14 days. Participants provided a faecal sample at day 0, day 7 (mid-supplementation), day 14 (end of supplementation) and 14 days after cessation of the supplement (day 28) for assessment of the number of viable LcS via microbial culture on selective media with confirmation using a colony-direct polymerase chain reaction and species-specific primers. RESULTS: The supplement was well tolerated by participants. No LcS colonies were recovered from participants prior to ingestion of the fermented milk drink. All participants had recoverable LcS colonies at day 7 and day 14, with a mean recovery of 6.5±1.1 and 6.4±1.1 log10 CFU/g of faeces (mean±SD) at each time point respectively. LcS was detectable in only one sample at 14 days following the cessation of supplementation. CONCLUSIONS: Live LcS is recoverable in faeces from healthy Australian adults following daily ingestion of a fermented milk drink.

Loss of Cardioprotective Effects at the ADAMTS7 Locus as a Result of Gene-Smoking Interactions.

BACKGROUND: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate interaction of smoking behavior, a potent lifestyle factor, with genotypes that have been shown to associate with CHD risk. METHODS: We analyzed data on 60 919 CHD cases and 80 243 controls from 29 studies for gene-smoking interactions for genetic variants at 45 loci previously reported to be associated with CHD risk. We also studied 5 loci associated with smoking behavior. Study-specific gene-smoking interaction effects were calculated and pooled using fixed-effects meta-analyses. Interaction analyses were declared to be significant at a P value of <1.0×10-3 (Bonferroni correction for 50 tests). RESULTS: We identified novel gene-smoking interaction for a variant upstream of the ADAMTS7 gene. Every T allele of rs7178051 was associated with lower CHD risk by 12% in never-smokers (P=1.3×10-16) in comparison with 5% in ever-smokers (P=2.5×10-4), translating to a 60% loss of CHD protection conferred by this allelic variation in people who smoked tobacco (interaction P value=8.7×10-5). The protective T allele at rs7178051 was also associated with reduced ADAMTS7 expression in human aortic endothelial cells and lymphoblastoid cell lines. Exposure of human coronary artery smooth muscle cells to cigarette smoke extract led to induction of ADAMTS7. CONCLUSIONS: Allelic variation at rs7178051 that associates with reduced ADAMTS7 expression confers stronger CHD protection in never-smokers than in ever-smokers. Increased vascular ADAMTS7 expression may contribute to the loss of CHD protection in smokers.

Nontypeable Haemophilus influenzae and chronic obstructive pulmonary disease: a review for clinicians.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. In the lower airways of COPD patients, bacterial infection is a common phenomenon and Haemophilus influenzae is the most commonly identified bacteria. Haemophilus influenzae is divided into typeable and nontypeable (NTHi) strains based on the presence or absence of a polysaccharide capsule. While NTHi is a common commensal in the human nasopharynx, it is associated with considerable inflammation when it is present in the lower airways of COPD patients, resulting in morbidity due to worsening symptoms and increased frequency of COPD exacerbations. Treatment of lower airway NTHi infection with antibiotics, though successful in the short term, does not offer long-term protection against reinfection, nor does it change the course of the disease. Hence, there has been much interest in the development of an effective NTHi vaccine. This review will summarize the current literature concerning the role of NTHi infections in COPD patients and the consequences of using prophylactic antibiotics in patients with COPD. There is particular focus on the rationale, findings of clinical studies and possible future directions of NTHi vaccines in patients with COPD.

Associations of coronary artery calcified plaque density with mortality in type 2 diabetes: the Diabetes Heart Study.

BACKGROUND: Coronary artery calcified plaque (CAC) is strongly predictive of cardiovascular disease (CVD) events and mortality, both in general populations and individuals with type 2 diabetes at high risk for CVD. CAC is typically reported as an Agatston score, which is weighted for increased plaque density. However, the role of CAC density in CVD risk prediction, independently and with CAC volume, remains unclear. METHODS: We examined the role of CAC density in individuals with type 2 diabetes from the family-based Diabetes Heart Study and the African American-Diabetes Heart Study. CAC density was calculated as mass divided by volume, and associations with incident all-cause and CVD mortality [median follow-up 10.2 years European Americans (n = 902, n = 286 deceased), 5.2 years African Americans (n = 552, n = 93 deceased)] were examined using Cox proportional hazards models, independently and in models adjusted for CAC volume. RESULTS: In European Americans, CAC density, like Agatston score and volume, was consistently associated with increased risk of all-cause and CVD mortality (p ≤ 0.002) in models adjusted for age, sex, statin use, total cholesterol, HDL, systolic blood pressure, high blood pressure medication use, and current smoking. However, these associations were no longer significant when models were additionally adjusted for CAC volume. CAC density was not significantly associated with mortality, either alone or adjusted for CAC volume, in African Americans. CONCLUSIONS: CAC density is not associated with mortality independent from CAC volume in European Americans and African Americans with type 2 diabetes.

Distinct Gene Expression Patterns between Nasal Mucosal Cells and Blood Collected from Allergic Rhinitis Sufferers.

BACKGROUND: Investigations of gene expression in allergic rhinitis (AR) typically rely on invasive nasal biopsies (site of inflammation) or blood samples (systemic immunity) to obtain sufficient genetic material for analysis. New methodologies to circumvent the need for invasive sample collection offer promise to further the understanding of local immune mechanisms relevant in AR. METHODS: A within-subject design was employed to compare immune gene expression profiles obtained from nasal washing/brushing and whole blood samples collected during peak pollen season. Twelve adults (age: 46.3 ± 12.3 years) with more than a 2-year history of AR and a confirmed grass pollen allergy participated in the study. Gene expression analysis was performed using a panel of 760 immune genes with the NanoString nCounter platform on nasal lavage/brushing cell lysates and compared to RNA extracted from blood. RESULTS: A total of 355 genes were significantly differentially expressed between sample types (9.87 to -9.71 log2 fold change). The top 3 genes significantly upregulated in nasal lysate samples were Mucin 1 (MUC1), Tight Junction Protein 1 (TJP1), and Lipocalin-2 (LCN2). The top 3 genes significantly upregulated in blood samples were cluster of differentiation 3e (CD3E), FYN Proto-Oncogene Src Family Tyrosine Kinase (FYN) and cluster of differentiation 3d (CD3D). CONCLUSIONS: Overall, the blood and nasal lavage samples showed vastly distinct gene expression profiles and functional gene pathways which reflect their anatomical and functional origins. Evaluating immune gene expression of the nasal mucosa in addition to blood samples may be beneficial in understanding AR pathophysiology and response to allergen challenge.

Effect of 8-weeks prebiotics/probiotics supplementation on alcohol metabolism and blood biomarkers of healthy adults: a pilot study.

PURPOSE: Modulating gut bacteria via regular prebiotics/probiotics consumption may improve the metabolism of acute alcohol ingestion. This study investigated the impact of 8-weeks prebiotics/probiotics supplementation on microbiome changes and responses to acute alcohol consumption. METHODS: 38 participants (21 females, 23.6 ± 3.4 kg m-2, mean ± SD) attended the laboratory on two occasions separated by an 8-week intervention period. On each of these visits, a dose of alcohol (0.40 ± 0.04 g kg-1, Vodka + Soda-Water) was consumed over 10 min. Breath alcohol concentration was sampled over 5 h and alcohol pharmacokinetics was analysed using WinNonlin non-compartmental modelling (C max, t max, AUClast). For the intervention, participants were randomised to receive Placebo + Placebo (PLA), Placebo + Prebiotics (PRE), Probiotics + Placebo (PRO), or Probiotics + Prebiotics (SYN) in a double-blinded manner. Probiotics were a commercially available source of Lactobacillus acidophilus (NCFM®) and Bifidobacterium lactis (Bi-07). Prebiotics were a commercially available source of Larch Gum (from Larix occidentalis). Placebo was microcrystalline cellulose. Each visit, participants provided a stool sample, which was analysed to determine the presence of L. acidophilus and B. lactis. Differences between trials were analysed using paired samples t tests. RESULTS: Increased counts for at least one bacterial strain (L. acidophilus or B. lactis) were observed for all participants on SYN (n = 10) and PRO (n = 10) trials. No difference in C max or t max was observed between trials when analysed by treatment condition or microbiome outcome. A significant decrease in AUClast was observed between trials for PLA (p = 0.039) and PRE (p = 0.030) treatments, and when increases in at least one bacterial strain (p = 0.003) and no microbiome changes (p = 0.016) were observed. CONCLUSION: Consumption of probiotics appears to alter faecal counts of supplemental bacterial strains in otherwise healthy individuals. However, translation to any possible beneficial impact on alcohol metabolism remains to be elucidated.

Enteroendocrine and adipokine associations with type 2 diabetes: Phenotypic risk scoring approaches.

BACKGROUND AND AIM: The contribution of gut-derived factors to the mechanisms linking obesity and metabolic disease remains under-investigated. The aim of the current study was to examine the associations between glucagon and enteroendocrine signaling and type 2 diabetes (T2D) using a derived risk score approach. To compare the relative importance of the enteroendocrine system, associations between adipokine measures and T2D were also investigated. METHODS: A total of 130 individuals with T2D and 161 individuals without T2D were included in the study. Circulating concentrations of enteroendocrine (glucagon, ghrelin, glucagon-like peptide-1, and gastric inhibitory peptide) and adipokine mediators (adiponectin, leptin, resistin, visfatin, and adipsin) were measured. Standard scores (Z-scores) were determined for each measure and enteroendocrine risk scores (ERS) and adipokine risk scores (ARS) calculated based on summation of the component measures. Associations between both the ERS and ARS and T2D status were assessed using logistic regression models. RESULTS: The ERS was significantly associated with T2D status in an adjusted model (odds ratio: 1.36; 95% confidence interval [CI]: 1.08-1.72; P = 0.009). Associations between the ARS and T2D status were not independent of age, sex, and body mass index (odds ratio: 1.21; 95%CI: 0.99-1.47; P = 0.06). Quantification of risk across ERS tertiles revealed that individuals with an ERS in the upper tertile were 10 times more likely (CI: 3.23-32.73; P < 0.001) to have T2D. CONCLUSIONS: These data support an association between enteroendocrine signaling and T2D. Use of the ERS as a potential tool for classifying individuals with metabolic syndrome as high or low risk for T2D development is being considered.

The Post-Exercise Inflammatory Response to Repeated-Sprint Running in Hypoxia.

This study investigated the acute inflammatory response to a repeat-sprint training session in hypoxia. Eleven amateur team-sport athletes completed a repeat-sprint training in hypoxia (RSH) protocol (4 sets of 4x4-s running sprints) in both normoxia and normobaric hypoxia (FiO2 0.145 to simulate an altitude of 3000 m) on separate days. Participants provided venous blood samples prior to (PRE), immediately after (POST), and 3 h after (3 h) completion of the protocol, and capillary blood lactate samples were taken upon arrival, at PRE, and at POST. Distance was recorded for each sprint. Venous blood samples were analysed to determine plasma concentrations of cytokines IL-1ß, IL-1ra, IL-6, IL-8, IL-10, and TNFα. There was no interaction or main effect of condition for any cytokine (p > 0.05). However, time effects indicated that IL-10 was decreased by an average of 19% across the two experimental trials at 3 h compared to POST (p = 0.04), IL-6 increased by 55% from PRE to POST (p = 0.03) then decreased by 43% from POST to 3 h (p = 0.02), and IL-8 decreased by 30% from PRE to POST (p = 0.04) and was further reduced at 3 h compared to POST (by an additional 23%; p = 0.02). A time × condition interaction (p = 0.03) indicated that lactate was higher in hypoxia. There was no interaction effect or effect of condition for sprint distance (p > 0.05). These results suggest that team-sport athletes can perform a RSH session without increasing inflammation when compared to the same training session performed in normoxia.

Immune Response in Women during Exercise in the Heat: A Spotlight on Oral Contraception.

This study compared the immune and stress response of oral contraceptive users (WomenOC; n = 9) to normally-menstruating women (WomenNM; n = 9) at rest and during exercise in temperate (TEMP; 22°C) and hot (HEAT; 35°C) conditions. Participants performed a 3-stage cycling trial in each condition at 90% (Stage 1; 30 min), 135% (Stage 2; 15 min), and 180% (Stage 3; 7.5 min) of lactate threshold 1. C-reactive protein (CRP) and immune cell counts were measured at rest, and serum cytokines (IL-1ß, IL-1RA, IL-6, IL-8, IL-10, and TNF-α) and salivary cortisol were evaluated before and after exercise in both the TEMP and HEAT conditions. There were no differences in resting immune cell counts between groups, nor any differences in cortisol or any of the pro- or anti-inflammatory cytokines measured at rest or after completion of the exercise trials (p > 0.05). However, a trend for a higher resting CRP concentration was observed in WomenOC relative to WomenNM (1.102 ± 1.182 and 0.326 ± 0.228, respectively, p = 0.07). The results obtained in the current study indicate similar immunoendocrine function in WomenOC and WomenNM both at rest and after exercise in temperate and hot environments.

A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease.

Obesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.