ABSTRACT
INTRODUCTION: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. METHODS: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB. RESULTS: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups. CONCLUSIONS: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB. TRIAL REGISTRATION NUMBER: ISRCTN11616770.
Subject(s)
Diphosphonates , Osteitis Deformans , Humans , Diphosphonates/adverse effects , Osteitis Deformans/complications , Osteitis Deformans/drug therapy , Osteitis Deformans/genetics , Sequestosome-1 Protein/genetics , Zoledronic Acid/therapeutic use , Genetic Testing , BiomarkersABSTRACT
The human microbiota functions at the interface between diet, medication-use, lifestyle, host immune development and health. It is therefore closely aligned with many of the recognised modifiable factors that influence bone mass accrual in the young, and bone maintenance and skeletal decline in older populations. While understanding of the relationship between micro-organisms and bone health is still in its infancy, two decades of broader microbiome research and discovery supports a role of the human gut microbiome in the regulation of bone metabolism and pathogenesis of osteoporosis as well as its prevention and treatment. Pre-clinical research has demonstrated biological interactions between the microbiome and bone metabolism. Furthermore, observational studies and randomized clinical trials have indicated that therapeutic manipulation of the microbiota by oral administration of probiotics may influence bone turnover and prevent bone loss in humans. In this paper, we summarize the content, discussion and conclusions of a workshop held by the Osteoporosis and Bone Research Academy of the Royal Osteoporosis Society in October, 2020. We provide a detailed review of the literature examining the relationship between the microbiota and bone health in animal models and in humans, as well as formulating the agenda for key research priorities required to advance this field. We also underscore the potential pitfalls in this research field that should be avoided and provide methodological recommendations to facilitate bridging the gap from promising concept to a potential cause and intervention target for osteoporosis.
Subject(s)
Gastrointestinal Microbiome , Microbiota , Osteoporosis , Probiotics , Animals , Bone and Bones/metabolism , Gastrointestinal Microbiome/physiology , Osteoporosis/metabolism , Osteoporosis/prevention & control , Probiotics/therapeutic useABSTRACT
Janus kinase inhibitors (JAKi) are an exciting option for the treatment of rheumatoid arthritis (RA) but little is known about their safety and tolerability in patients with existing respiratory disorders. The objective was to compare pulmonary safety of JAKi versus rituximab in patients with concurrent interstitial lung disease (ILD) or bronchiectasis. We performed a retrospective electronic patient record review of patients with known ILD or bronchiectasis commencing JAKi or rituximab for the treatment of RA. Patients initiating treatment from January 2016 to February 2020 were included. Respiratory events (hospitalization or death from a respiratory cause) were compared using Kaplan-Meier survival analysis. We analysed patients who received JAKi (n = 28) and rituximab (n = 19) for a mean (SD) of 1.1 (0.62) and 2.14 (1) years respectively. Patients were predominantly female (68%), anti-CCP antibody positive (94%) and non-smoking (89%) with a median (IQR) percentage predicted FVC at baseline of 100% (82-115%) and percentage predicted TLCO of 62% (54.5-68%). Respiratory events occurred in five patients treated with JAKi (18%; 5 hospitalizations, 2 deaths) and in four patients treated with rituximab (21%; 3 hospitalizations, 1 death). Respiratory event rates did not differ between groups (Cox-regression proportional hazard ratio = 1.38, 95% CI 0.36-5.28; p = 0.64). In this retrospective study, JAKi for the treatment of RA with existing ILD or bronchiectasis did not increase the rate of hospitalization or death due to respiratory causes compared to those treated with rituximab. JAK inhibition may provide a relatively safe option for RA in such patients.
Subject(s)
Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Janus Kinase Inhibitors/administration & dosage , Rituximab/administration & dosage , Aged , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/complications , Bronchiectasis/complications , Female , Hospitalization , Humans , Janus Kinase Inhibitors/adverse effects , Kaplan-Meier Estimate , Lung Diseases, Interstitial/complications , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Rituximab/adverse effectsABSTRACT
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.
Subject(s)
Bone Density/physiology , Gastrointestinal Microbiome/physiology , Gastrointestinal Tract/microbiology , Health Status , Osteoporosis/metabolism , Osteoporotic Fractures/metabolism , Absorptiometry, Photon/methods , Aged , Female , Humans , Male , Middle Aged , Osteoporosis/diagnosis , Osteoporosis/microbiology , Osteoporotic Fractures/diagnosis , Osteoporotic Fractures/microbiologyABSTRACT
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 .
Subject(s)
Body Composition , Exercise , Inflammatory Bowel Diseases/complications , Overweight/complications , Overweight/therapy , Resistance Training , Adult , Affect , Body Mass Index , Cross-Over Studies , Cytokines/blood , Female , Gastrointestinal Microbiome , Humans , Inflammatory Bowel Diseases/immunology , Inflammatory Bowel Diseases/microbiology , Inflammatory Bowel Diseases/psychology , Male , Prospective Studies , Quality of Life , Resistance Training/adverse effects , Young AdultABSTRACT
The objective was to determine plasma levels of pro- (IL-12p70/IL-6) and anti-inflammatory (IL-10) cytokines before and after cycle ergometer training in healthy control (HC) and people with multiple sclerosis (pwMS), and to correlate plasma cytokines with physical/mental health. Study participants cycled for 30 min at 65-75% age-predicted maximal heart rate, twice a week for 8 weeks during supervised sessions. We determined that plasma IL-10 expression was lower in pwMS, compared to HCs, and that exercise augmented IL-10 in pwMS to baseline levels in HCs. Furthermore, plasma isolated from pwMS displayed enhanced expression of the pro-inflammatory cytokines IL-12p70/IL-6. Plasma cytokine signatures correlated with physical/mental health. Overall, this study highlights the potential of a short-term exercise programme to regulate circulating cytokine profiles with relevance to pwMS.
Subject(s)
Bicycling , Exercise Therapy/methods , Interleukin-10/blood , Multiple Sclerosis/blood , Multiple Sclerosis/therapy , Adult , Bicycling/physiology , Ergometry , Humans , Interleukin-12 Subunit p35/blood , Interleukin-6/bloodABSTRACT
Following publication the authors informed the Journal that the published version of this article contained a mistake. All occurrences of pg/µl found in the original article should be changed to pg/L. The original article has been corrected. The correction has no impact on the conclusions drawn in the manuscript.
ABSTRACT
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.
Subject(s)
Athletes , Exercise , Feces/microbiology , Feeding Behavior , Gastrointestinal Microbiome , Body Mass Index , Case-Control Studies , Female , Humans , Male , Young AdultABSTRACT
In this pilot study, we investigate whether a routine cycle ergometry training programme has therapeutic potential in individuals with multiple sclerosis (MS) by improving quality of life (QOL) and depressive symptomatology, while ameliorating cognitive disturbances. Healthy volunteers and MS patients cycled for 30 min at 65-75% age-predicted maximal heart rate on a recumbent ergometer, with this session repeated twice a week for 8 weeks. QOL, depressive symptomatology and cognitive function were assessed pre- and post-exercise using the MS Quality of Life-54 (MSQOL-54) questionnaire, 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) questionnaire and the Cambridge Neuropsychological Test Automated Battery (CANTAB), respectively. We determined that QOL was lower in MS patients, compared to healthy subjects, with a reduction in physical and mental health summary scores observed. Exercise improved both physical and mental health scores in MS patients. In support of this, exercise was shown to reduce depressive symptomatology in MS patients. Exercise was also associated with an improvement in visual sustained attention, executive function/cognitive flexibility and hippocampal-dependent visuospatial memory in patients. Overall, this study identifies a short-term exercise programme that improves physical and mental health, while reducing depressive symptomatology and cognitive dysfunction in MS.
Subject(s)
Cognition , Depression/therapy , Exercise Therapy , Multiple Sclerosis/psychology , Multiple Sclerosis/therapy , Quality of Life , Adult , Body Mass Index , Body Weight , Depression/physiopathology , Exercise/psychology , Exercise Therapy/instrumentation , Female , Humans , Immunologic Factors/therapeutic use , Male , Multiple Sclerosis/physiopathology , Neuropsychological Tests , Physical Fitness , Pilot Projects , Treatment OutcomeABSTRACT
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.
Subject(s)
Exercise , Gastrointestinal Diseases/prevention & control , Gastrointestinal Motility/physiology , Health Promotion , Immunity, Mucosal/physiology , Physical Fitness , Cardiovascular Physiological Phenomena , Guidelines as Topic , Humans , Quality of LifeABSTRACT
INTRODUCTION: Multiple myeloma (MM) is a systemic malignancy of plasma cells defined by monoclonal production of circulating immunoglobulins. Bone pain is a presenting feature in the majority of cases. Treatment may involve intravenous use of bisphosphonates, chemotherapy or haematopoietic stem cell transplantation. Here, we illustrate a first presentation of MM in a patient with mandibular pain and discuss radiographic, diagnostic and treatment challenges of orofacial issues in patients with MM. CASE REPORT: A 69-year-old lady presented to an emergency oral surgery clinic with a month-long history of unilateral left-sided pain in her jaw. Examination revealed a buccolingual swelling of 2cm diameter in the lower left premolar region. Radiographic images demonstrated a 2cm lytic lesion in her mandible corresponding with the symptomatic region. Aspiration of the lesion was performed and histological analysis indicated an abundance of atypical plasma cells. Subsequent biopsy revealed sheets of plasmacytoid cells suggesting evidence of a plasmacytoma. Skeletal survey, bone marrow biopsy and serum analysis confirmed the presence of MM. DISCUSSION: MM, although a systemic malignancy, can present via a variety of orofacial manifestations. The presence of a lytic lesion on plain radiographs should alert the dental practitioner to the possibility of the diagnosis. Treatment of orofacial bone pain may respond to intravenous bisphosphonates but care must be taken to avoid osteonecrosis of the jaw. CONCLUSION: This case is an important reminder of the potential oral presentations of MM and underlines the importance of radiographic evaluation in patients with atypical symptoms and presentations.
Subject(s)
Mandibular Neoplasms/diagnosis , Multiple Myeloma/diagnosis , Aged , Biopsy , Female , Humans , Ilium/diagnostic imaging , Mandible/diagnostic imaging , Mandible/pathology , Mandibular Neoplasms/complications , Mandibular Neoplasms/pathology , Multiple Myeloma/complications , Multiple Myeloma/pathology , Pain/etiology , Radiography , Skull/diagnostic imagingABSTRACT
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.
Subject(s)
Defibrillators/supply & distribution , Out-of-Hospital Cardiac Arrest/therapy , Allied Health Personnel/education , Cross-Sectional Studies , Death, Sudden, Cardiac/prevention & control , Defibrillators/statistics & numerical data , Equipment Safety/statistics & numerical data , Football/statistics & numerical data , Humans , Ireland , Maintenance/statistics & numerical data , Professional Practice/statistics & numerical data , Soccer/statistics & numerical data , Sports Medicine/instrumentation , Surveys and Questionnaires , Time FactorsSubject(s)
Exercise , Gastrointestinal Microbiome , Sports Medicine/trends , Athletes , Diet , HumansABSTRACT
Systemic vasculitides are a range of conditions characterized by inflammation of blood vessels which may manifest as single organ or life-threatening multisystem disease. The treatment of systemic vasculitis varies depending on the specific disease but historically has involved initial treatment with high dose glucocorticoids alone or in conjunction with other immunosuppressive agents. Prolonged glucocorticoid treatment is frequently required as maintenance treatment. Patients with small and large vessel vasculitis are at increased risk of fracture. Osteoporosis may occur due to intrinsic factors such as chronic inflammation, impaired renal function and to a large extent due to pharmacological therapy with high dose glucocorticoid or combination treatments. This review will outline the known mechanism of bone loss in vasculitis and will summarize factors attributing to fracture risk in different types of vasculitis. Osteoporosis treatment with specific consideration for patients with vasculitis will be discussed. The use of glucocorticoid sparing immunosuppressive agents in the treatment of systemic vasculitis is a significant area of ongoing research. Adjunctive treatments are used to reduce cumulative doses of glucocorticoids and therefore may significantly decrease the associated fracture risk in patients with vasculitis. Lastly, we will highlight the many unknowns in the relation between systemic vasculitis, its treatment and bone health and will outline key research priorities for this field.
Subject(s)
Fractures, Bone , Osteoporosis , Systemic Vasculitis , Vasculitis , Bone Density , Fractures, Bone/chemically induced , Glucocorticoids/adverse effects , Humans , Immunosuppressive Agents/adverse effects , Inflammation/chemically induced , Osteoporosis/chemically induced , Osteoporosis/complications , Osteoporosis/drug therapy , Systemic Vasculitis/chemically induced , Systemic Vasculitis/drug therapy , Vasculitis/chemically induced , Vasculitis/drug therapyABSTRACT
Objectives: The aim was to describe a modern National Health Service (NHS) Scotland cohort of patients with GCA over 12 months of care to include clinical presentation, practices relating to assessment and treatment, and specifically, the use of tocilizumab. Methods: A multicentre audit of patients newly diagnosed with GCA between November 2019 and October 2021 was established on behalf of the Scottish Society for Rheumatology. Clinical data were collected retrospectively by rheumatology teams at participating NHS centres using electronic patient records. An extended cohort of patients from NHS Lothian was examined to investigate outcomes of tocilizumab use for >1 year. Results: Sixty-three patients from three NHS Scotland health boards were included, with analysis of data from 216 clinic episodes. Mean follow-up was 371 days. Mean age was 71 years; 62% were female. The most common presenting features were headache (93.6%), scalp tenderness (82.5%) and ocular symptoms (24%). At baseline, 63% of patients had at least one existing risk factor for adverse outcomes from high-dose CS use, namely hypertension (57.1%), diabetes (24%) and osteoporosis (11%). Thirty per cent of all patients (19 of 63) received tocilizumab, with only 11% (7 of 63) receiving tocilizumab owing to glucocorticoid risk factors at baseline. One-quarter of all patients (16 of 63) experienced relapse of GCA during follow-up, of whom six were subsequently treated with tocilizumab. Conclusion: This multicentre audit demonstrates that despite its availability for patients with risk factors for CS adversity and those who suffer relapse of GCA, tocilizumab is used in less than one-quarter of patients who might benefit. The reasons for this require further exploration.
ABSTRACT
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.
ABSTRACT
Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB), but little is known about the clinical characteristics of those with early disease. Radionuclide bone scans, biochemical markers of bone turnover, and clinical characteristics were analyzed in SQSTM1 mutation carriers who took part in the Zoledronic acid in the Prevention of Paget's disease (ZiPP) study. We studied 222 individuals, of whom 54.9% were female, with mean ± SE age of 50.1 ± 0.6 years. Twelve SQSTM1 mutations were observed, including p.Pro392Leu, which was present in 141 of 222 (63.5%) subjects. Bone scan examination revealed evidence of PDB in 20 subjects (9.0%), ten of whom (50%) had a single affected site. Participants with lesions were older than those without lesions but the difference was not significant (53.6 ± 9.1 versus 49.8 ± 8.9; p = .07). The mean age of participants with lesions was not significantly different from the age at which their parents were diagnosed with PDB (55 years versus 59 years, p = .17). All individuals with lesions were asymptomatic. Serum concentrations of total alkaline phosphatase (ALP) normalized to the upper limit of normal in each center were higher in those with lesions (0.75 ± 0.69 versus 0.42 ± 0.29 arbitary units; p < .0001). Similar findings were observed for other biochemical markers of bone turnover, but the sensitivity of ALP and other markers in detecting lesions was poor. Asymptomatic PDB is present in about 9% of SQSTM1 mutation carriers by the fifth decade. Further follow-up of this cohort will provide important information on the natural history of early PDB and its response to treatment. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Subject(s)
Adaptor Proteins, Signal Transducing , Osteitis Deformans , Sequestosome-1 Protein , Adaptor Proteins, Signal Transducing/genetics , Female , Humans , Male , Middle Aged , Mutation , Osteitis Deformans/epidemiology , Osteitis Deformans/genetics , Sequestosome-1 Protein/genetics , Zoledronic AcidABSTRACT
OBJECTIVES: Compositional and functional adaptions occur in the gut microbiome in response to habitual physical activity. The response of the gut microbiome to sustained, intense exercise in previously active individuals, however, is unknown. This study aimed to prospectively explore the gut microbiome response of four well-trained male athletes to prolonged, high intensity trans-oceanic rowing, describing changes in microbial diversity, abundance and metabolic capacity. DESIGN: A prospective, repeated-measures, within-subject report. METHODS: Serial stool samples were obtained from four male athletes for metagenomic whole-genome shotgun sequencing to record microbial community structure and relevant functional gene profiles before, during and after a continuous, unsupported 33-day, 5000 km transoceanic rowing race. Calorific intake and macronutrient composition were recorded by validated food frequency questionnaire and anthropometry was determined by body composition analysis and cardiorespiratory testing. RESULTS: Microbial diversity increased throughout the ultra-endurance event. Variations in taxonomic composition included increased abundance of butyrate producing species and species associated with improved metabolic health, including improved insulin sensitivity. The functional potential of bacterial species involved in specific amino and fatty acid biosynthesis also increased. Many of the adaptions in microbial community structure and metaproteomics persisted at three months follow up. CONCLUSIONS: These findings demonstrate that prolonged, intense exercise positively influences gut microbial diversity, increases the relative abundance of some bacterial species and up-regulates the metabolic potential of specific pathways expressing microbial gene products. These adaptions may play a compensatory role in controlling the physiological stress associated with sustained exertion as well as negating the deleterious consequences accompanying endurance exercise.