Nicholas P. West

Obesity, inflammation, and the gut microbiota

As the prevalence of obesity and associated disease continues to rise and concerns for the spiralling economic and social costs also escalate, innovative management strategies beyond primary prevention and traditional lifestyle interventions are urgently needed. The biological basis of disease is one avenue for further exploration in this context. Several key inflammatory markers have been consistently associated with both obesity and risk of adverse outcomes in obesity-associated diseases, which suggests that a persistent, low-grade, inflammatory response is a potentially modifiable risk factor. In this Review, we provide evidence supporting perturbation of the intestinal microbiota and changes in intestinal permeability as potential triggers of inflammation in obesity. Further characterisation of the mechanisms underpinning the triggers of such inflammatory responses in overweight and obese individuals could offer unique opportunities for intervention strategies to help ameliorate the risk of obesity-associated disease.

Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes

BackgroundProbiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora. Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals. There is a paucity of data regarding the effectiveness of probiotics in this cohort. The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology, self-reported illness symptoms and immunity in healthy well trained individuals.MethodsCompetitive cyclists (64 males and 35 females; age 35 ± 9 and 36 ± 9 y, VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1, mean ± SD) were randomised to either probiotic (minimum 1 × 109Lactobacillus fermentum (PCC®) per day) or placebo treatment for 11 weeks in a double-blind, randomised, controlled trial. The outcome measures were faecal L. fermentum counts, self-reported symptoms of illness and serum cytokines.ResultsLactobacillus numbers increased 7.7-fold (90% confidence limits 2.1- to 28-fold) more in males on the probiotic, while there was an unclear 2.2-fold (0.2- to 18-fold) increase in females taking the probiotic. The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group. However, there was a substantial 0.7 (0.2 to 1.2) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males, which became more pronounced as training load increased. The load (duration×severity) of lower respiratory illness symptoms was less by a factor of 0.31 (99%CI; 0.07 to 0.96) in males taking the probiotic compared with placebo but increased by a factor of 2.2 (0.41 to 27) in females. Differences in use of cold and flu medication mirrored these symptoms. The observed effects on URTI had too much uncertainty for a decisive outcome. There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines.ConclusionL. fermentum may be a useful nutritional adjunct for healthy exercising males. However, uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved.Trial registrationThe trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12611000006943).

The effect of exercise on innate mucosal immunity

Methods The authors conducted a prospective observational study comparing salivary lactoferrin and lysozyme concentration over 5 months (chronic changes) in elite rowers (n=17, mean age 24.3±4.0 years) with sedentary individuals (controls) (n=18, mean age=27.2±7.1 years) and a graded exercise test to exhaustion (acute changes) with a cohort of elite rowers (n=11, mean age 24.7±4.1). Results Magnitudes of differences and changes were interpreted as a standardised (Cohens) effect size (ES). Lactoferrin concentration in the observational study was approximately 60% lower in rowers than control subjects at baseline (7.9±1.2 µg/ml mean±SEM, 19.4±5.6 µg/ml, p=0.05, ES=0.68, ‘moderate’) and at the midpoint of the season (6.4±1.4 µg/ml mean ± SEM, 21.5±4.2 µg/ml, p=0.001, ES=0.89, ‘moderate’). The concentration of lactoferrin at the end of the study was not statistically significant (p=0.1) between the groups. There was no significant difference between rowers and control subjects in lysozyme concentration during the study. There was a 50% increase in the concentration of lactoferrin (p=0.05, ES=1.04, ‘moderate’) and a 55% increase in lysozyme (p=0.01, ES=3.0, ‘very large’) from pre-exercise to exhaustion in the graded exercise session. Conclusion Lower concentrations of these proteins may be indicative of an impairment of innate protection of the upper respiratory tract. Increased salivary lactoferrin and lysozyme concentration following exhaustive exercise may be due to a transient activation response that increases protection in the immediate postexercise period.

Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals

BACKGROUND & AIMS To examine the effect of supplementation with probiotics on respiratory and gastrointestinal illness in healthy active men and women. METHODS A randomised double-blind placebo-controlled trial was conducted. Four hundred and sixty five participants (241 males; age 35 ± 12 y (mean ± SD) and 224 females; age 36 ± 12 y) were assigned to one of three groups: Group 1 - Bifidobacterium animalis subsp. lactis Bl-04 (Bl-04) 2.0 × 10(9)colony forming units per day, CFU per day, Group 2 - Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07 (NCFM & Bi-07) 5 × 10(9) CFU each per day) or Group 3 - placebo mixed in a drink. RESULTS The risk of an upper respiratory illness episode was significantly lower in the Bl-04 group (hazard ratio 0.73; 95% confidence interval 0.55-0.95; P = 0.022) compared to placebo. There was no significant difference in illness risk between the NCFM & Bi-07 group (hazard ratio 0.81; 0.62-1.08; P = 0.15) and the placebo group. There was a 0.7 and 0.9 month delay in the median time to an illness episode in the Bl-04 and NCFM & Bi-07 groups respectively compared to placebo (placebo 2.5 months; Bl-04 3.2 months; NCFM & Bi-07 3.4 months). There were insufficient GI illness episodes for analysis. The NCFM & Bi-07 group but not the Bl-04 group undertook significantly more physical activity (8.5%; 6.7%-10%; P < 0.003) than the placebo group. CONCLUSION The probiotic Bl-04 appears to be a useful nutritional supplement in reducing the risk of URTI in healthy physically-active adults. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry: Number ACTRN12611000130965.

Sleep/wake behaviour of endurance cyclists before and during competition

Abstract Good sleep is critical for optimising recovery and athletic performance. Yet, few studies have investigated how athletes sleep before and during competition. The aim of this study was to determine whether such sleep is poorer than that before a usual training day. Twenty-one male endurance cyclists’ (age: 19.9 ± 1.7 years) sleep/wake behaviour was assessed using wrist activity monitors for 11 nights, including a six-night baseline training phase, three nights before competition and two nights during competition. Cyclists had less sleep on the night before competition (6.5 ± 0.9 h) and during the first night of competition (6.8 ± 0.8 h) than at baseline (7.4 ± 0.6 h). Cyclists also went to bed and woke up earlier during competition than at baseline. Competition schedules and competition itself can disrupt the sleep/wake behaviour of athletes during competition. Future investigations should examine sleep during three stages of competition (i.e. before, during and after competition). This will help coaches develop a greater understanding of how sleep changes during different phases of competition and enable them to plan post-competition training programmes to ensure appropriate rest and recovery is obtained.

Probiotics supplementation for athletes: clinical and physiological effects

Abstract Probiotic supplementation has traditionally focused on gut health. However, in recent years, the clinical applications of probiotics have broadened to allergic, metabolic, inflammatory, gastrointestinal and respiratory conditions. Gastrointestinal health is important for regulating adaptation to exercise and physical activity. Symptoms such as nausea, bloating, cramping, pain, diarrhoea and bleeding occur in some athletes, particularly during prolonged exhaustive events. Several studies conducted since 2006 examining probiotic supplementation in athletes or highly active individuals indicate modest clinical benefits in terms of reduced frequency, severity and/or duration of respiratory and gastrointestinal illness. The likely mechanisms of action for probiotics include direct interaction with the gut microbiota, interaction with the mucosal immune system and immune signalling to a variety of organs and systems. Practical issues to consider include medical and dietary screening of athletes, sourcing of recommended probiotics and formulations, dose–response requirements for different probiotic strains, storage, handling and transport of supplements and timing of supplementation in relation to travel and competition.

Importance of Standardized DXA Protocol for Assessing Physique Changes in Athletes.

PURPOSE The implications of undertaking DXA scans using best practice protocols (subjects fasted and rested) or a less precise but more practical protocol in assessing chronic changes in body composition following training and a specialized recovery technique were investigated. METHODS Twenty-one male cyclists completed an overload training program, in which they were randomized to four sessions per week of either cold water immersion therapy or control groups. Whole-body DXA scans were undertaken with best practice protocol (Best) or random activity protocol (Random) at baseline, after 3 weeks of overload training, and after a 2-week taper. Magnitudes of changes in total, lean and fat mass from baseline-overload, overload-taper and baseline-taper were assessed by standardization (Δmean/SD). RESULTS The standard deviations of change scores for total and fat-free soft tissue mass (FFST) from Random scans (2-3%) were approximately double those observed in the Best (1-2%), owing to extra random errors associated with Random scans at baseline. There was little difference in change scores for fat mass. The effect of cold water immersion therapy on baseline-taper changes in FFST was possibly harmful (-0.7%; 90% confidence limits ±1.2%) with Best scans but unclear with Random scans (0.9%; ±2.0%). Both protocols gave similar possibly harmful effects of cold water immersion therapy on changes in fat mass (6.9%; ±13.5% and 5.5%; ±14.3%, respectively). CONCLUSIONS An interesting effect of cold water immersion therapy on training-induced changes in body composition might have been missed with a less precise scanning protocol. DXA scans should be undertaken with Best.

Does Hydrotherapy Help or Hinder Adaptation to Training in Competitive Cyclists

PURPOSE Cold water immersion (CWI) may be beneficial for acute recovery from exercise, but it may impair long-term performance by attenuating the stimuli responsible for adaptation to training. We compared effects of CWI and passive rest on cycling performance during a simulated cycling grand tour. METHODS Thirty-four male endurance-trained competitive cyclists were randomized to CWI for four times per week for 15 min at 15°C or control (passive recovery) groups for 7 d of baseline training, 21 d of intensified training, and an 11-d taper. Criteria for completion of training and testing were satisfied by 10 cyclists in the CWI group (maximal aerobic power, 5.13 ± 0.21 W·kg; mean ± SD) and 11 in the control group (5.01 ± 0.41 W·kg). Each week, cyclists completed a high-intensity interval cycling test and two 4-min bouts separated by 30 min. CWI was performed four times per week for 15 min at 15°C. RESULTS Between baseline and taper, cyclists in the CWI group had an unclear change in overall 4-min power relative to control (2.7% ± 5.7%), although mean power in the second effort relative to the first was likely higher for the CWI group relative to control (3.0% ± 3.8%). The change in 1-s maximum mean sprint power in the CWI group was likely beneficial compared with control (4.4% ± 4.2%). Differences between groups for the 10-min time trial were unclear (-0.4% ± 4.3%). CONCLUSION Although some effects of CWI on performance were unclear, data from this study do not support recent speculation that CWI is detrimental to performance after increased training load in competitive cyclists.

Increased intestinal permeability as a risk factor for type 2 diabetes.

AIM Relationships between the intestinal microbiota, intestinal permeability and inflammation in the context of risk for obesity-associated disease continue to be of interest. The aim of the study was to examine the associations between intestinal permeability and type 2 diabetes (T2D). METHODS A total of 130 individuals with T2D (age: 57.5±6.2 years (mean±SD); BMI: 30.4±3.2; 45% female) and 161 individuals without T2D (age: 37.4±12.5 years; BMI: 25.1±3.9; 65% female) were included in the study. Assessment of intestinal permeability included measurement of circulating lipopolysaccharide (LPS), LPS-binding protein (LBP) and intestinal fatty acid binding protein (iFABP) concentrations, which were used for calculation of a derived permeability risk score (PRS). Associations between permeability measures and T2D status were assessed using logistic regression models. RESULTS LBP (∼34%, P<0.001), iFABP (∼46%, P<0.001) and the PRS (∼24% P<0.001) were all significantly higher in the T2D affected individuals. Individuals with a PRS in the upper tertile were 5.07 times more likely (CI: 1.72-14.95; P=0.003) to have T2D when models were adjusted for age, sex and BMI. There was a trend towards improved prediction when including the PRS in models containing age, sex and BMI (AUC: 0.954 versus 0.962; P=0.06). CONCLUSION These data demonstrate differences in measures of intestinal permeability between individuals with and without T2D. The utility of using intestinal permeability measures as a tool for predicting T2D risk in at risk individuals should be further investigated.

‘Aussie normals’: an a priori study to develop clinical chemistry reference intervals in a healthy Australian population

Summary Development of reference intervals is difficult, time consuming, expensive and beyond the scope of most laboratories. The Aussie Normals study is a direct a priori study to determine reference intervals in healthy Australian adults. All volunteers completed a health and lifestyle questionnaire and exclusion was based on conditions such as pregnancy, diabetes, renal or cardiovascular disease. Up to 91 biochemical analyses were undertaken on a variety of analytical platforms using serum samples collected from 1856 volunteers. We report on our findings for 40 of these analytes and two calculated parameters performed on the Abbott ARCHITECTci8200/ci16200 analysers. Not all samples were analysed for all assays due to volume requirements or assay/instrument availability. Results with elevated interference indices and those deemed unsuitable after clinical evaluation were removed from the database. Reference intervals were partitioned based on the method of Harris and Boyd into three scenarios, combined gender, males and females and age and gender. We have performed a detailed reference interval study on a healthy Australian population considering the effects of sex, age and body mass. These reference intervals may be adapted to other manufacturers analytical methods using method transference.