The exercise and diet-microbiome paradigm: influences of physical activity and dietary nutrition on the human gut microbiome

Introduction: Revolutionary insights of the human microbiome, the conglomeration of microorganisms that stably occupy an expansive array of anatomical locations of the human body, have certified the phenomenon as an integral component of human biology. As progress has been made in elucidating the various factors of influence that the microbiome imposes on human health, it has become apparent that modulation of the community structure and functional activity of the microbiome is an essential step in utilizing these microbes as an element of intervention in healthcare. Advancement in understanding of how the microbiome is manipulated is accordingly of great interest and importance. Methods: Physical activity is a recently emergent prospective modulator of the human intestinal microbiome. This development in microbiome-host interaction presents great potential, but has presently been investigated in limited depth. To expand the understanding of this biological dynamic we engaged the subject with focus on metabolic function of the microbiome, utilising advanced computation methods and molecular technologies. Our approach has sought to address multiple aspects of exercise induced microbiome alteration, and accordingly was conducted with randomized control trials and prospective observational study designs. Results: This work describes further evidence that physical exercise has a role in directing the community structure and metabolic activity of the gut microbiome. Our inspection of professional athletes, whose prolonged engagement in rigorous exercise grants perspective of the extreme end of the spectrum of physical activity, revealed a divergent microbiome from that of more sedentary controls. Metabolic pathways from the athletes were configured to offer enhanced energy recovery from the intestinal environment. Quantified metabolomic phenotyping of this system similarly revealed that the athlete microbiome had a favourable profile of SCFA enrichment. Examination of structured short-term exercise on exercise naïve individuals revealed subtle alterations of the microbiome, both in terms of phylogenetic composition and metabolic output. In our investigation it was also observed for the first time that supplementation of whey protein resulted in an alteration of the virome. Further sequencing of the supplement itself revealed a highly similar viral composition to the participants, suggesting that whey protein, a widely used supplement, is directly transmitting virus particles. To explore the implementation of exercise as a supportive intervention for health conditions related to the GI system, patients with inflammatory bowel disease (IBD) were recruited for a short-term exercise intervention study. While minimal changes in the composition of the IBD patients’ gut microbiome were identified, the patients were shown to undergo the treatment without insult to, or perturbation of their disease state. This important finding illustrates that sufferers of IBD can engage in physical exercise, reaping the well-known health benefits from the activity, without obvious influence on the gut microbiome. Elucidation of the longitudinal effects of exercise on the gut microbiome was achieved through the examination of two individuals engaging in exercise over the course of six months. Through this N of 1 style of study, resources were concentrated on the two participants, enabling the acquisition of much greater detail on the proposed question. Here again, it was observed that while the participants were rewarded with improvements in health parameters, changes of the gut microbiome were subtle. Complementing the impressive results produced from initial investigations of professional athletes, effort was put forth to apply advanced computational approaches to the previously generated data in order to advance understanding of the athlete microbiome. A novel algorithm designed to predict adherence to healthy dietary habits based on metabolomic profiling was used to better define dietary influence on the metabolomic dynamics of the gut environment. Separately, a computational modelling method centred on Flux Balance Analysis generated models of microbial metabolic exchange within the athletes and corresponding controls. Conclusions: The findings supporting this thesis have immediate relevance in the area of athleticism, with implications for professional athletes and individuals casually engaged in exercise. There is further impetus provided for continued investigation of the athlete microbiome, the influence of prolonged periods of exercise on populations with low fitness levels, and the impact of dietary supplement derived microbe transmission

Metabolic phenotyping of the human microbiome

peer-reviewedThe human microbiome has been identified as having a key role in health and numerous diseases. Trillions of microbial cells and viral particles comprise the microbiome, each representing modifiable working elements of an intricate bioactive ecosystem. The significance of the human microbiome as it relates to human biology has progressed through culture-dependent (for example, media-based methods) and, more recently, molecular (for example, genetic sequencing and metabolomic analysis) techniques. The latter have become increasingly popular and evolved from being used for taxonomic identification of microbiota to elucidation of functional capacity (sequencing) and metabolic activity (metabolomics). This review summarises key elements of the human microbiome and its metabolic capabilities within the context of health and disease

Gut microbiota: implications for sports and exercise medicine

Technological progress in high-throughput sequencing and advanced bioinformatic techniques, have facilitated a deeper understanding of the gut microbial influence on human health. Collectively known as the gut microbiota, the trillions of microbes including bacteria, viruses and fungi, which reside within the gut, are now recognised as significant contributors to human (host) health. Patients with non-communicable diseases such as metabolic syndrome, obesity and inflammatory bowel disease, demonstrate distinct microbial alterations. This has prompted vigorous pursuit of the mechanisms by which this microbial ‘organ’ influences host health. This branch of medicine has already revealed exciting avenues for disease treatment, from the discovery of novel antibiotics to the treatment of recurrent Clostridium difficile infection. The scale and spectrum of microbial influence is substantial and elegant studies have linked the presence or absence of specific microbes with immunity, neurodevelopment and even behavioural disturbances. The potential impact of microbiome science extends to the specialties of Sports Medicine and particularly to Exercise Medicine

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

peer-reviewedBackground 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 β-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

Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage – a Randomized Placebo-Controlled Trial to assess Safety, Tolerability and Feasibility

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos \u3e5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusions: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences

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

Protein quality and quantity influence the effect of dietary fat on weight gain and tissue partitioning via host-microbiota changes

ACKNOWLEDGMENTS This work was supported by a research grant from Science Foundation Ireland (SFI) under grant SFI/16/BBSRC/3389, BBSRC under grant number BB/ P009875/1 (to K.N.N. and J.R.S.), and in part by SFI and the Department of Agriculture, Food and Marine under grant 16/RC/3835 (to VistaMilk). We thank Conall Strain, David Mannion, and John Leech for contributing to the metabolomics analysis. We thank Alina Kondrashina for help with the Milliplex system.Peer reviewedPublisher PD

Destruction of formic acid by soft X-rays in star-forming regions

Formic acid is much more abundant in the solid state, both in interstellar ices and cometary ices, than in the interstellar gas (ice/gas ~ 10^{4}) and this point remains a puzzle. The goal of this work is to experimentally study ionization and photodissociation processes of HCOOH (formic acid), a glycine precursor molecule. The measurements were taken at the Brazilian Synchrotron Light Laboratory (LNLS), employing soft X-ray photons from toroidal grating monochromator TGM) beamline (200 - 310 eV). Mass spectra were obtained using photoelectron photoion coincidence (PEPICO) method. Kinetic energy distributions and abundances for each ionic fragment have been obtained from the analysis of the corresponding peak shapes in the mass spectra. Photoionization and photodissociation cross sections were also determined. Due to the large photodissociation cross section of HCOOH it is possible that in PDRs regions, just after molecules evaporation from the grain surface, formic acid molecules are almost totally destroyed by soft X-rays, justifying the observed low abundance of HCOOH in the gaseous phase. The preferential path for the glycine formation from formic acid may be through the ice phase reaction. Keywords: HCOOH; Photoionization; X-rays; Astrochemistry.Comment: 9 pages, 7 figures, 2 tables. Accepted to be printed in A&

Learned vocal variation is associated with abrupt cryptic genetic change in a parrot species complex

<div><p>Contact zones between subspecies or closely related species offer valuable insights into speciation processes. A typical feature of such zones is the presence of clinal variation in multiple traits. The nature of these traits and the concordance among clines are expected to influence whether and how quickly speciation will proceed. Learned signals, such as vocalizations in species having vocal learning (e.g. humans, many birds, bats and cetaceans), can exhibit rapid change and may accelerate reproductive isolation between populations. Therefore, particularly strong concordance among clines in learned signals and population genetic structure may be expected, even among continuous populations in the early stages of speciation. However, empirical evidence for this pattern is often limited because differences in vocalisations between populations are driven by habitat differences or have evolved in allopatry. We tested for this pattern in a unique system where we may be able to separate effects of habitat and evolutionary history. We studied geographic variation in the vocalizations of the crimson rosella (<em>Platycercus elegans</em>) parrot species complex. Parrots are well known for their life-long vocal learning and cognitive abilities. We analysed contact calls across a <em>ca</em> 1300 km transect encompassing populations that differed in neutral genetic markers and plumage colour. We found steep clinal changes in two acoustic variables (fundamental frequency and peak frequency position). The positions of the two clines in vocal traits were concordant with a steep cline in microsatellite-based genetic variation, but were discordant with the steep clines in mtDNA, plumage and habitat. Our study provides new evidence that vocal variation, in a species with vocal learning, can coincide with areas of restricted gene flow across geographically continuous populations. Our results suggest that traits that evolve culturally can be strongly associated with reduced gene flow between populations, and therefore may promote speciation, even in the absence of other barriers.</p> </div

In vitro–in vivo Validation of Stimulatory Effect of Oat Ingredients on Lactobacilli

peer reviewedThe prebiotic activity of a commercially available oat product and a novel oat ingredient, at similar -glucan loads, was tested using a validated in vitro gut model (M-SHIME®). The novel oat ingredient was tested further at lower -glucan loads in vitro, while the commercially available oat product was assessed in a randomised, single-blind, placebo-controlled, and cross-over human study. Both approaches focused on healthy individuals with mild hypercholesterolemia. In vitro analysis revealed that both oat products strongly stimulated Lactobacillaceae and Bifidobacteriaceae in the intestinal lumen and the simulated mucus layer, and corresponded with enhanced levels of acetate and lactate with cross-feeding interactions leading to an associated increase in propionate and butyrate production. The in vitro prebiotic activity of the novel oat ingredient remained at lower -glucan levels, indicating the prebiotic potential of the novel oat product. Finally, the stimulation of Lactobacillus spp. was confirmed during the in vivo trial, where lactobacilli abundance significantly increased in the overall population at the end of the intervention period with the commercially available oat product relative to the control product, indicating the power of in vitro gut models in predicting in vivo response of the microbial community to dietary modulation