The nonindustrialised microbiome in a modern world.

The microbiome contributes to human development and maturation, and is essential for maintenance of health and prevention of disease. While the human genome encodes one's identity, the microbiome - also individually unique - provides a window on one's lifestyle and exposure to environmental variables. The microbiome thus serves as a biomarker of host health and a driver of certain diseases. However, current understanding of the gut microbiome is largely based on studies of industrialised peoples of North America and Europe. Gaps in knowledge of the microbiomes of other groups, particularly those in developing or nonindustrialised societies, are important, particularly in view of contrasting epidemiological risks of acquiring chronic inflammatory and metabolic disorders. Here, we explore underlying mechanisms of microbiome differences and whether the potential benefits of nonindustrialised microbiome can be realised in a modern world.

Gut microbiota alterations associated with reduced bone mineral density in older adults.

OBJECTIVE: To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS: Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS: We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION: Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.

Moderate-intensity aerobic and resistance exercise is safe and favorably influences body composition in patients with quiescent Inflammatory Bowel Disease: a randomized controlled cross-over trial.

BACKGROUND: Overweight and metabolic problems now add to the burden of illness in patients with Inflammatory Bowel Disease. We aimed to determine if a program of aerobic and resistance exercise could safely achieve body composition changes in patients with Inflammatory Bowel Disease. METHODS: A randomized, cross-over trial of eight weeks combined aerobic and resistance training on body composition assessed by Dual Energy X-ray Absorptiometry was performed. Patients in clinical remission and physically inactive with a mean age of 25 ± 6.5 years and Body Mass Index of 28.9 ± 3.8 were recruited from a dedicated Inflammatory Bowel Disease clinic. Serum cytokines were quantified, and microbiota assessed using metagenomic sequencing. RESULTS: Improved physical fitness was demonstrated in the exercise group by increases in median estimated VO2max (Baseline: 43.41mls/kg/min; post-intervention: 46.01mls/kg/min; p = 0.03). Improvement in body composition was achieved by the intervention group (n = 13) with a median decrease of 2.1% body fat compared with a non-exercising group (n = 7) (0.1% increase; p = 0.022). Lean tissue mass increased by a median of 1.59 kg and fat mass decreased by a median of 1.52 kg in the exercising group. No patients experienced a deterioration in disease activity scores during the exercise intervention. No clinically significant alterations in the α- and ß-diversity of gut microbiota and associated metabolic pathways were evident. CONCLUSIONS: Moderate-intensity combined aerobic and resistance training is safe in physically unfit patients with quiescent Inflammatory Bowel Disease and can quickly achieve favourable body compositional changes without adverse effects. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov; Trial number: NCT02463916 .

A Repeated-measures Case Series of Physiological Responses to a Transoceanic Rowing Race.

This repeated-measures case series describes the changes in cardiorespiratory fitness, body composition and systemic inflammation in 4 well-trained athletes pre- and post-completion of an unsupported transatlantic rowing race. The acute effects of endurance exercise have been well described previously, but the enduring consequences of ultra-endurance on the cardiorespiratory, metabolic and immune systems are largely unknown. This study explores these physiological adaptations following 2 weeks of recovery. Cardiorespiratory fitness testing, body composition analysis, and blood sampling for inflammatory cytokines were recorded immediately before race departure and repeated 14 days following race completion. Mean VO2max (ml/kg/min) was similar pre- (48.2±2.8) and post-race (46.7±1.5). Heart rate responses were equivalent at incremental workloads. Mean blood lactate (mmol/L) was higher at low to moderate power outputs and lower at maximal effort (14.6±1.85 vs. 13.1±2.5). Percentage body fat (17.7 ± 7.9 vs. 16.2±7.4) was analogous to pre-race analysis. Low-grade inflammation persisted, indicated by an increase in IL-1ß (69%), IL-8 (10%), TNF-α (8%), IL-6 (5.4%), and C-reactive protein (22.4%). VO2max and heart rate responses were similar pre- and post-race, but sub-maximal efficiency measures of cardiorespiratory fitness were consistent with persistent fatigue. Body composition had returned to baseline but low-grade systemic inflammation persisted. Persistent pro-inflammatory cytokinaemia is known to exert deleterious consequences on immune, metabolic, and psychological function. Adequate recovery is necessary to re-establish inflammatory homeostasis, and the results of this study may inform these decisions.

The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level.

OBJECTIVE: It is evident that the gut microbiota and factors that influence its composition and activity effect human metabolic, immunological and developmental processes. We previously reported that extreme physical activity with associated dietary adaptations, such as that pursued by professional athletes, is associated with changes in faecal microbial diversity and composition relative to that of individuals with a more sedentary lifestyle. Here we address the impact of these factors on the functionality/metabolic activity of the microbiota which reveals even greater separation between exercise and a more sedentary state. DESIGN: Metabolic phenotyping and functional metagenomic analysis of the gut microbiome of professional international rugby union players (n=40) and controls (n=46) was carried out and results were correlated with lifestyle parameters and clinical measurements (eg, dietary habit and serum creatine kinase, respectively). RESULTS: Athletes had relative increases in pathways (eg, amino acid and antibiotic biosynthesis and carbohydrate metabolism) and faecal metabolites (eg, microbial produced short-chain fatty acids (SCFAs) acetate, propionate and butyrate) associated with enhanced muscle turnover (fitness) and overall health when compared with control groups. CONCLUSIONS: Differences in faecal microbiota between athletes and sedentary controls show even greater separation at the metagenomic and metabolomic than at compositional levels and provide added insight into the diet-exercise-gut microbiota paradigm.

GREB1 genetic variants are associated with bone mineral density in Caucasians.

Gaining an understanding of factors contributing to bone quality is key to the development of effective preventative treatments for osteoporosis and reduction in osteoporotic fractures. Oestrogen is a strong regulator of bone remodelling which maintains skeletal structural integrity. The growth regulation by oestrogen in breast cancer 1 (GREB1) gene, with an as yet undefined function, is an early response gene in the oestrogen-regulated pathway. Suggestive evidence of linkage with bone mineral density (BMD) variation has been reported with D2S168, located telomeric of GREB1. The aim of this study was to determine if genetic variation within GREB1 was associated with BMD variation at two sites with high fracture rates-the lumbar spine (LS) and the femoral neck (FN). Informative GREB1 single-nucleotide polymorphisms (SNPs) (n = 12) were selected for genotyping and tested for association in a family-based dataset (n = 508 individuals from 229 families). Significantly associated SNPs were tested further in a postmenopausal dataset from the same geographic region (n = 477 individuals). One intronic SNP, rs5020877, was significantly associated with LS and FN BMD in the family-based dataset (P ≤ 0.005). The association was not observed in the postmenopausal dataset (P > 0.017); however, rs10929757 was significantly associated with FN BMD (P = 0.006). Markers, rs5020877 and rs10929757, were constituent SNPs in one GREB1 linkage disequilibrium block, although not historically correlated (r 2 = 0.07). Our findings suggest that GREB1 is a novel gene target for osteoporosis genetics and needs to be investigated further.

Exercise, fitness, and the gut.

PURPOSE OF REVIEW: Exercise and gut symptomatology have long been connected. The possibility that regular exercise fosters intestinal health and function has been somewhat overlooked in the scientific literature. In this review, we summarize current knowledge and discuss a selection of recent, relevant, and innovative studies, hypotheses and reviews that elucidate a complex topic. RECENT FINDINGS: The multiorgan benefits of regular exercise are extensive. When taken in moderation, these benefits transcend improved cardio-respiratory fitness and likely reach the gut in a metabolic, immunological, neural, and microbial manner. This is applicable in both health and disease. However, further work is required to provide safe, effective recommendations on physical activity in specific gastrointestinal conditions. SUMMARY: Challenging methodology investigating the relationship between exercise and gut health should not deter from exploring exercise in the promotion of gastrointestinal health.

Comparison of single CT scan assessment of bone mineral density, vascular calcification and fat mass with standard clinical measurements in renal transplant subjects: the ABC HeART study.

BACKGROUND: Despite limitations of routine methods, Clinical Practice Guidelines support the assessment of bone mineral density (BMD) and vascular calcification in renal transplant recipients. Changes in fat mass also occur post-transplantation, although they are traditionally difficult to measure accurately. We report the feasibility, convenience and accuracy of measuring the above 3 parameters using a novel CT protocol. METHODS: We conducted a cross-sectional study of 64 first renal allograft recipients (eGFR > 30 ml/min/1.73 m(2)). Quantitative CT (QCT) BMD analysis was conducted using CT lumbar spine (GE Medical Systems Lightspeed VCT & Mindways QCT Pro Bone Mineral Densitometry System Version 4.2.3) to calculate spinal volumetric BMD and compared with standard DXA calculated areal BMD at the spine, hip and distal forearm. Abdominal aortic calcification was assessed by semi-quantitative Aortic Calcification Index (ACI) method and compared with lateral lumbar x-ray Kappuila score and pulse wave velocity (PWV). Visceral and subcutaneous adipose tissue volume (Osirix 16 Ver 3.7.1) was compared with BMI. RESULTS: Participants were 61 % male, had a mean age of 47 years, median ESKD duration of 5.4 years and a mean eGFR of 54 ml/min. iDXA median T-score at proximal femur was -1.2 and at lumbar spine was -0.2. Median QCT Trabecular T-score at lumbar spine was -1.2. The percent of subjects with a T-score of < 2.5 by site and method was DXA Proximal Femur: 7 %, DXA distal radius: 17 %, DXA spine: 9 %, QCT (American College of Radiology cutoffs): 9 %. CT derived ACI correlated with PWV (r = 0.29, p = 0.02), pulse wave pressure (r = 0.51, p < 0.001), QCT Trabecular (-0.31, p = 0.01) and cortical volumetric BMD and history of cardiovascular events (Mann-Whitney U, p = 0.02). Both visceral and subcutaneous adipose tissue correlated with BMI (r = 0.63 & 0.64, p < 0.001). CONCLUSIONS: Single CT scan triple assessment of BMD, vascular calcification and body composition is an efficient, accurate and convenient method of risk factor monitoring post renal transplantation.

Exercise and associated dietary extremes impact on gut microbial diversity.

OBJECTIVE: The commensal microbiota, host immunity and metabolism participate in a signalling network, with diet influencing each component of this triad. In addition to diet, many elements of a modern lifestyle influence the gut microbiota but the degree to which exercise affects this population is unclear. Therefore, we explored exercise and diet for their impact on the gut microbiota. DESIGN: Since extremes of exercise often accompany extremes of diet, we addressed the issue by studying professional athletes from an international rugby union squad. Two groups were included to control for physical size, age and gender. Compositional analysis of the microbiota was explored by 16S rRNA amplicon sequencing. Each participant completed a detailed food frequency questionnaire. RESULTS: As expected, athletes and controls differed significantly with respect to plasma creatine kinase (a marker of extreme exercise), and inflammatory and metabolic markers. More importantly, athletes had a higher diversity of gut micro-organisms, representing 22 distinct phyla, which in turn positively correlated with protein consumption and creatine kinase. CONCLUSIONS: The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.

Prepared for sudden cardiac arrest? A cross-sectional study of automated external defibrillators in amateur sport.

INTRODUCTION: Sudden cardiac arrest (SCA) is a rare but tragic part of professional and amateur sport. Following multiple high profile deaths in professional sport over the past two decades, there has been a significant trend towards the widespread availability of automated external defibrillators (AEDs) at amateur sports grounds. OBJECTIVES: To examine the availability of AEDs in amateur sports clubs in Cork, Ireland, and to investigate club practices with respect to the purchase, accessibility, maintenance and use of AEDs. DESIGN: A cross-sectional survey of 218 amateur Gaelic Athletic Association (GAA), soccer and rugby clubs was conducted between July and September 2012. Club committee representatives answered a 22-point questionnaire. RESULTS: 126 GAA clubs and 28 soccer and 17 rugby (n=171) clubs were enrolled in this study. A total of 81.3% of amateur clubs own an AED. We estimate an AED-use rate of one AED use for every 54.5 years an AED is available. Almost 50% of club representatives thought the location of their club AED could be improved while 12.9% of clubs admitted to not maintaining their club AED on a regular basis. CONCLUSIONS: A large proportion of amateur clubs in Cork City and County own an AED. Many clubs engage in regular maintenance and storage of AEDs. However, this study identifies several areas for improvement in facilitating a secure chain of survival for players in the event of an SCA.

Contact sport and osteoarthritis.

Osteoarthritis (OA) is the most common joint disease in the world and the single largest cause of disability for those over 18 years. It affects more than twice as many people as does cardiac disease, and increases in incidence and prevalence with age. Animal and human studies have shown no evidence of increased risk of hip or knee OA with moderate exercise and in the absence of traumatic injury, sporting activity has a protective effect. One age-matched case control study found recreational runners who ran 12-14 miles per week for up to 40 years had no increase in radiological or symptomatic hip or knee OA. However, higher rates of hip OA occur in contact sports than in age-matched controls, with the highest rate in professional players. Soccer players with torn anterior cruciate ligaments (ACL) are more likely to develop knee OA than those with intact ACL. Early ACL repair reduces the risk of knee OA, but does not prevent it. Established injury prevention programmes have been refined to prevent injuries such as ACL rupture.

Injury surveillance during the 2010 IRB Women's Rugby World Cup.

OBJECTIVE: To assess and evaluate injuries sustained during the 2010 Women's Rugby World Cup. DESIGN: Prospective, cohort. PARTICIPANTS: 285 women rugby players. RESULTS: Incidence of match injury was 35.5/1000 player-hours; mean severity was 55.0 days and median severity 9 days. Only one training injury was reported. Knee-ligament injuries were the most common (15%) and resulted in most days lost (43%). The tackle was the cause of most injuries. CONCLUSIONS: The risk of injury in international rugby is significantly lower for women than for men. Further research is required to assess knee-ligament injuries in women's rugby.

Epidemiological study of injuries in men's international under-20 rugby union tournaments.

OBJECTIVE: To determine the incidence, nature, and causes of match injuries sustained during Under-20 (U-20) international rugby. DESIGN: Prospective cohort study; definitions and procedures were compliant with the international consensus statement for epidemiological studies in rugby. SETTING: 2008 and 2010 IRB U-20 Junior World Championships and Junior World Rugby Trophies. PARTICIPANTS: Nine hundred forty-one players representing 35 international teams. ASSESSMENT OF RISK FACTORS: Injuries reported as functions of playing position and nature and cause of injury. MAIN OUTCOME MEASURES: Incidence, location, type, severity, and causes of match injuries. RESULTS: Incidence of injury was 57.2 per 1000 player-match-hours (forwards, 55.3; backs, 59.4) with a mean severity of 22.4 days (forwards, 27.7; backs, 16.9) and a median severity of 6 days (forwards, 8; backs, 6). Lower limb ligament (25.3%) and muscle (21.3%) pathologies were the main injuries. Most injuries were acute (90.4%) and sustained during tackles (45.1%) and collisions (17.7%). CONCLUSIONS: The study showed that the overall risk of injury for players in international U-20 rugby is significantly lower than that reported at the full international level of play; the nature and causes of injury at U-20 are similar to those at the full international level of play.

The effects of sustained fitness improvement on the gut microbiome: A longitudinal, repeated measures case-study approach.

The athlete gut microbiome differs from that of non-athletes in its composition and metabolic function. Short-term fitness improvement in sedentary adults does not replicate the microbiome characteristics of athletes. The objective of this study was to investigate whether sustained fitness improvement leads to pronounced alterations in the gut microbiome. This was achieved using a repeated-measures, case-study approach that examined the gut microbiome of two initially unfit volunteers undertaking progressive exercise training over a 6-month period. Samples were collected every two weeks, and microbiome, metabolome, diet, body composition, and cardiorespiratory fitness data were recorded. Training culminated in both participants completing their respective goals (a marathon or Olympic-distance triathlon) with improved body composition and fitness parameters. Increases in gut microbiota α-diversity occurred with sustained training and fluctuations occurred in response to training events (eg, injury, illness, and training peaks). Participants' BMI reduced during the study and was significantly associated with increased urinary measurements of N-methyl nicotinate and hippurate, and decreased phenylacetylglutamine. These results suggest that sustained fitness improvements support alterations to gut microbiota and physiologically-relevant metabolites. This study provides longitudinal analysis of the gut microbiome response to real-world events during progressive fitness training, including intercurrent illness and injury.

Moderate chronic kidney disease in women is associated with fracture occurrence independently of osteoporosis.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased risk of fragility fracture but whether this is independent of osteoporosis is unclear. METHODS: We conducted a retrospective cross-sectional study of 1,702 female patients referred for dual-energy X-ray absorptiometry (DXA) scanning (Lunar IDXA) between September 2006 and April 2007. Estimated glomerular filtration rate (eGFR; ml/min/1.73 m(2)) by Modification of Diet in Renal Disease was calculated within 1 year (median interval 4 weeks) of the DXA scan. The independent association of self-reported fracture occurrence with eGFR category was assessed using multivariate logistic regression. RESULTS: Mean age (SD) was 61.7 (10.8) years; mean eGFR (SD) was 68.8 (12.2). The percentages of subjects with an eGFR of 75-89, 60-74, 30-59 and <30 was 34, 45, 20 and 0.8%, respectively. Forty-seven percent had osteoporosis. Mean T scores for the above eGFR categories were -2.2, -2.3, -2.5 and -3.0, respectively (p trend <0.001). Osteoporosis was significantly associated with eGFR on univariate analysis but not following adjustment for age. The percentage of patients with a fracture (29%) and with multiple prior fractures (3.5%) was higher at lower eGFR (p < 0.001, χ(2) test). The adjusted odds ratios (95% confidence interval) of any prior fracture for eGFR 75-89, 60-74 and 30-59 were 1.0 (reference), 1.2 (0.9-1.6) and 1.4 (1.0-1.9), respectively, adjusting simultaneously for age, T score, risk factors and treatment for osteoporosis. CONCLUSION: Moderate CKD is a significant independent predictor of fracture occurrence.

Epidemiological study of injuries in international Rugby Sevens.

OBJECTIVE: To assess incidence, nature, and causes of injuries sustained in international Rugby Sevens. DESIGN: Prospective cohort: definitions and procedures were compliant with the consensus statement for epidemiological studies in rugby union. SETTING: 2008/2009 International Rugby Board Sevens World Series (8 tournaments) and Rugby World Cup Sevens 2009. PARTICIPANTS: Two hundred ninety players, representing 12 countries. ASSESSMENT OF RISK FACTORS: Injuries sustained as function of playing position and nature, cause, and time of onset. MAIN OUTCOME MEASURES: Number, location, diagnosis, severity, and cause of injuries: incidence (injuries/1000 player-hours) and severity (days absence from training/competition) of injuries. RESULTS: One hundred four injuries were recorded during 578 team games (979.1 player-match hours), which equates to 0.18 injuries per team match, 0.96 injuries per team per tournament, or 106.2 injuries per 1000 player-hours (95% confidence interval, 87.8-128.9). These injuries had a mean severity of 45 days and a median severity of 24 days. The lower limb (70%) and joint (non-bone)/ligament (52%) were the most common site and type of injury. Most match injuries were acute (93%) and resulted from contact (78%) events; being tackled (34%) and running (22%) were the most common causes of injury. CONCLUSIONS: Results indicated that the risk of injury from international Rugby Sevens was higher than that reported for international 15-a-side rugby; in particular, the severity of injury was significantly higher. A need for further research into the reasons for the high average severity of injury and the development of injury prevention strategies for ankle and knee ligament injuries in Rugby Sevens were indicated.

Risk of injury associated with rugby union played on artificial turf.

The aim of this study was to compare the incidence, nature, and cause of injuries sustained in rugby union played on artificial turf and grass. The study comprised a two-season investigation of match injuries sustained by six teams competing in Hong Kong's Division 1 and training injuries sustained by two teams in the English Premiership. Injury definitions and recording procedures were compliant with the international consensus statement on epidemiological studies of injuries in rugby union. There were no significant differences in the overall incidence (rate ratio = 1.42; P = 0.134) or severity (P = 0.620) of match injuries sustained on the two surfaces. The lower limb and joint (non-bone)/ligament injuries were the most common location and type of match injury on both surfaces; the incidence of anterior cruciate ligament injuries was nearly four times higher on artificial turf than grass but the difference was not statistically significant (rate ratio = 3.82; P = 0.222). There were no significant differences in the overall incidence (rate ratio = 1.36; P = 0.204) or severity (P = 0.302) of training injuries sustained on artificial turf and grass. The lower limb and muscle/tendon injuries were the most common location and type of training injury on both surfaces. The results indicate that the overall risks of injury on artificial turf are not significantly different from those experienced on grass; however, the difference in the incidence of anterior cruciate ligament injuries on the two surfaces is worthy of further study.

Microbiome and health implications for ethnic minorities after enforced lifestyle changes.

Modern lifestyles increase the risk of chronic diseases, in part by modifying the microbiome, but the health effects of lifestyles enforced on ethnic minorities are understudied1-3. Lifestyle affects the microbiome early in life, when the microbiome is assembled and the immune system is undergoing maturation4-6. Moreover, the influence of lifestyle has been separated from genetic and geographic factors by studies of genetically similar populations and ethnically distinct groups living in the same geographic location7-11. The lifestyle of Irish Travellers, an ethnically distinct subpopulation, changed with legislation in 2002 that effectively ended nomadism and altered their living conditions. Comparative metagenomics of gut microbiomes shows that Irish Travellers retain a microbiota similar to that of non-industrialized societies. Their microbiota is associated with non-dietary factors and is proportionately linked with risk of microbiome-related metabolic disease. Our findings suggest there are microbiome-related public health implications when ethnic minorities are pressured to change lifestyles.

Dynamic Blood-Brain Barrier Regulation in Mild Traumatic Brain Injury.

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.