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.

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.

Reducing inappropriate non-steroidal anti-inflammatory prescription in primary care patients with chronic kidney disease.

Purpose The purpose of this paper is to reduce inappropriate non-steroidal anti-inflammatory prescribing in primary care patients with chronic kidney disease (CKD). Once diagnosed, CKD management involves delaying progression to end stage renal failure and preventing complications. It is well established that non-steroidal anti-inflammatories have a negative effect on kidney function and consequently, all nephrology consensus groups suggest avoiding this drug class in CKD. Design/methodology/approach The sampling criteria included all practice patients with a known CKD risk factor. This group was refined to include those with an estimated glomerular filtration rate (eGFR)<60 ml/min per 1.73m2 (stage 3 CKD or greater). Phase one analysed how many prescriptions had occurred in this group over the preceding three months. The intervention involved creating an automated alert on at risk patient records if non-steroidal anti-inflammatories were prescribed and discussing the rationale with practice staff. The re-audit phase occurred three months' post intervention. Findings The study revealed 728/7,500 (9.7 per cent) patients at risk from CKD and 158 (2.1 per cent) who were subsequently found to have an eGFR<60 ml/min, indicating=stage 3 CKD. In phase one, 10.2 per cent of at risk patients had received a non-steroidal anti-inflammatory prescription in the preceding three months. Additionally, 6.2 per cent had received non-steroidal anti-inflammatories on repeat prescription. Phase two post intervention revealed a significant 75 per cent reduction in the total non-steroidal anti-inflammatories prescribed and a 90 per cent reduction in repeat non-steroidal anti-inflammatory prescriptions in those with CKD. Originality/value The study significantly reduced non-steroidal anti-inflammatory prescription in those with CKD in primary care settings. It also created a CKD register within the practice and an enduring medication alert system for individuals that risk nephrotoxic non-steroidal anti-inflammatory prescription. It established a safe, reliable and efficient process for reducing morbidity and mortality, improving quality of life and limiting the CKD associated health burden.

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.

Four men in a boat: Ultra-endurance exercise alters the gut microbiome.

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.