Exertional heat stress promotes the presence of bacterial DNA in plasma: A counterbalanced randomised controlled trial.

OBJECTIVES: The primary aim was to explore the impact of exertional-heat stress (EHS) promoted exercise-associated bacteraemia. A secondary aim was to examine if an amino acid beverage (AAB) intervention may mitigate exercise-associated bacteraemia. DESIGN: Counterbalanced randomised control trial. METHODS: Twenty endurance trained male participants completed two randomised EHS trials. On one occasion, participants consumed a 237 mL AAB twice daily for 7 days prior, immediately before and every 20 min during EHS (2 h running at 60 % V̇O2max in 35 °C). On the other occasion, a water volume control (CON) equivalent was consumed. Whole blood samples were collected pre- and immediately post-EHS, and were analysed for plasma DNA concentration by fluorometer quantification after microbial extraction, and bacterial relative abundance by next generation 16s rRNA gene sequencing. RESULTS: Increased concentration of microbial DNA in plasma pre- to post-EHS was observed on CON (pre-EHS 0.014 ng/µL, post-EHS 0.039 ng/µL) (p < 0.001) and AAB (pre-EHS 0.015 ng/µL, post-EHS 0.031 ng/µL) (p < 0.001). The magnitude of change from pre- to post-exercise on AAB was 40 % lower, but no significant difference was observed versus CON (p = 0.455). Predominant bacterial groups identified included: phyla-Proteobacteria (88.0 %), family-Burkholderiaceae (59.1 %), and genus-Curvibacter (58.6 %). No significant variation in absolute and relative change in α-diversity and relative abundance for phyla, family, and genus bacterial groups was observed in AAB versus CON. CONCLUSIONS: The increased presence of microbial-bacterial DNA in systemic circulation in response to EHS appears positive in all participants. An amino acid beverage supplementation period prior to and consumption during EHS did not provide significant attenuation of EHS-associated bacteraemia.

The increase in core body temperature in response to exertional-heat stress can predict exercise-induced gastrointestinal syndrome.

Utilizing metadata from existing exertional and exertional-heat stress studies, the study aimed to determine if the exercise-associated increase in core body temperature can predict the change in exercise-induced gastrointestinal syndrome (EIGS) biomarkers and exercise-associated gastrointestinal symptoms (Ex-GIS). Endurance-trained individuals completed 2 h of running exercise in temperate (21.2-30.0°C) to hot (35.0-37.2°C) ambient conditions (n = 132 trials). Blood samples were collected pre- and post-exercise to determine the change in gastrointestinal integrity biomarkers and systemic inflammatory cytokines. Physiological and thermoregulatory strain variables were assessed every 10-15 min during exercise. The strength of the linear relationship between maximal (M-Tre) and change (Δ Tre) in rectal temperature and EIGS variables was determined via Spearman's rank correlation coefficients. While the strength of prediction was determined via simple and multiple linear regression analyses dependent on screened EIGS and Ex-GIS confounding factors. Significant positive correlations between Tre maximum (M-Tre) and change (Δ Tre) with I-FABP (rs = 0.434, p < 0.001; and rs = 0.305, p < 0.001; respectively), sCD14 (rs = 0.358, p < 0.001; and rs = 0.362, p < 0.001), systemic inflammatory response profile (SIR-Profile) (p < 0.001), and total Ex-GIS (p < 0.05) were observed. M-Tre and Δ Tre significantly predicted (adjusted R2) magnitude of change in I-FABP (R2(2,123)=0.164, p < 0.001; and R2(2,119)=0.058, p = 0.011; respectively), sCD14 (R2(2,81)=0.249, p < 0.001; and R2(2,77)=0.214, p < 0.001), SIR-Profile (p < 0.001), and total Ex-GIS (p < 0.05). Strong to weak correlations were observed between M-Tre and Δ Tre with plasma concentrations of I-FABP, sCD14, SIR-Profile, and Ex-GIS in response to exercise. M-Tre and Δ Tre can predict the magnitude of these EIGS variables and Ex-GIS in response to exercise.

The impact of 48 h high carbohydrate diets with high and low FODMAP content on gastrointestinal status and symptoms in response to endurance exercise, and subsequent endurance performance.

This study investigated the effects of a high carbohydrate diet, with varied fermentable oligo-, di-, and mono-saccharide and polyol (FODMAP) content, before endurance exercise on gastrointestinal integrity, motility, and symptoms; and subsequent exercise performance. Twelve endurance athletes were provided with a 48 h high carbohydrate (mean ± SD: 12.1 ± 1.8 g kg day-1) diet on two separate occasions, composed of high (54.8 ± 10.5 g day-1) and low FODMAP (3.0 ± 0.2 g day-1) content. Thereafter, participants completed a 2 h steady-state running exercise at 60% of V ˙ O 2 max (22.9 ± 1.2 °C, 46.4 ± 7.9% RH), followed by a 1 h distance performance test. Pre-exercise and every 20 min during steady-state exercise, 100 mL maltodextrin (10% w/v) solution was consumed. A 150 mL lactulose (20 g) solution was consumed 30 min into the distance performance test to determine orocecal transit time (OCTT) during exercise. Blood was collected pre- and post exercise to determine gastrointestinal integrity biomarkers (i.e., I-FABP, sCD14, and CRP). Breath hydrogen (H2) and gastrointestinal symptoms (GIS) were determined pre-exercise, every 15 min, during and throughout recovery. No differences in gastrointestinal integrity biomarkers, OCTT, or distance completed were observed between trials. Pre-exercise total-GIS (1.3 ± 2.9 vs. 4.3 ± 4.4), gut discomfort (9.9 ± 8.1 vs. 15.8 ± 9.0), and upper-GIS (2.8 ± 2.6 vs. 5.7 ± 4.8) during exercise were less severe on high carbohydrate low FODMAP (HC-LFOD) versus high carbohydrate high FODMAP (HC-HFOD) (p < 0.05). Gut discomfort (3.4 ± 4.4 vs. 0.2 ± 0.6) and total-GIS (4.9 ± 6.8 vs. 0.2 ± 0.6) were higher during recovery on HC-LFOD versus HC-HFOD (p < 0.05). The FODMAP content of a 48 h high carbohydrate diet does not impact gastrointestinal integrity or motility in response to endurance exercise. However, a high FODMAP content exacerbates GIS before and during exercise, but this does not impact performance outcomes.

Does Age Influence Gastrointestinal Status Responses to Exertional-heat Stress?

This meta-data exploration aimed to determine the impact of exertional-heat stress (EHS) on gastrointestinal status of masters age and young adult endurance athletes. Sixteen MASTERS (mean: 44y) and twenty-one YOUNG (26y) recreational endurance athletes completed 2 h of running at 60% ˙V O2max in 35˚C ambient conditions. Blood samples were collected pre-, immediately and 1 h post-EHS, and analyzed for markers of exercise-induced gastrointestinal syndrome (EIGS). Thermo-physiological measures and gastrointestinal symptoms (GIS) were recorded every 10-20 min during EHS. Peak Δ pre- to post-EHS did not substantially differ (p>0.05) between MASTERS and YOUNG for intestinal epithelial injury [I-FABP: 1652pg/ml vs. 1524pg/ml, respectively], bacterial endotoxic translocation [sCD14: -0.09µg/mL vs. 0.84µg/mL, respectively], lipopolysaccharide-binding protein [LBP: 0.26µg/mL vs. 1.76µg/mL, respectively], and systemic inflammatory response profile (SIR-Profile: 92.0arb.unit vs. 154arb.unit, respectively). A significantly higher peak Δ pre- to post-EHS in endogenous endotoxin anti-body IgM (p=0.042), and pro-inflammatory cytokine IL-1ß (p=0.038), was observed in YOUNG compared to MASTERS. No difference was observed between incidence (81% and 80%, respectively) and severity (summative accumulation: 21 and 30, respectively) of reported GIS during EHS between MASTERS and YOUNG. Pathophysiology of EIGS in response to EHS does not substantially differ with age progression, since masters and younger adult endurance athletes responded comparably.

Amino Acid-Based Beverage Interventions Ameliorate Exercise-Induced Gastrointestinal Syndrome in Response to Exertional-Heat Stress: The Heat Exertion Amino Acid Technology (HEAAT) Study.

The study aimed to determine the effects of two differing amino acid beverage interventions on biomarkers of intestinal epithelial integrity and systemic inflammation in response to an exertional-heat stress challenge. One week after the initial assessment, participants (n = 20) were randomly allocated to complete two exertional-heat stress trials, with at least 1 week washout. Trials included a water control trial (CON), and one of two possible amino acid beverage intervention trials (VS001 or VS006). On VS001 (4.5 g/L) and VS006 (6.4 g/L), participants were asked to consume two 237-ml prefabricated doses daily for 7 days before the exertional-heat stress, and one 237-ml dose immediately before, and every 20 min during 2-hr running at 60% maximal oxygen uptake in 35 °C ambient conditions. A water volume equivalent was provided on CON. Whole blood samples were collected pre-, immediately post-, 1 and 2 hr postexercise, and analyzed for plasma concentrations of cortisol, intestinal fatty acid protein, soluble CD14, and immunoglobulin M (IgM) by ELISA, and systemic inflammatory cytokines by multiplex. Preexercise resting biomarker concentrations for all variables did not significantly differ between trials (p > .05). A lower response magnitude for intestinal fatty acid protein (mean [95% CI]: 249 [60, 437] pg/ml, 900 [464, 1,336] pg/ml), soluble CD14 (-93 [-458, 272] ng/ml, 12 [-174, 197] ng/ml), and IgM (-6.5 [-23.0, 9.9] MMU/ml, -10.4 [-16.2, 4.7] MMU/ml) were observed on VS001 and V006 compared with CON (p < .05), respectively. Systemic inflammatory response profile was lower on VS001, but not VS006, versus CON (p < .05). Total gastrointestinal symptoms did not significantly differ between trials. Amino acid beverages' consumption (i.e., 4.5-6.4 g/L), twice daily for 7 days, immediately before, and during exertional-heat stress ameliorated intestinal epithelial integrity and systemic inflammatory perturbations associated with exercising in the heat, but without exacerbating gastrointestinal symptoms.

Effect of prebiotics, probiotics, and synbiotics on gastrointestinal outcomes in healthy adults and active adults at rest and in response to exercise-A systematic literature review.

Introduction: A systematic literature search was undertaken to assess the impact of pre-, pro-, and syn-biotic supplementation on measures of gastrointestinal status at rest and in response to acute exercise. Methods: Six databases (Ovid MEDLINE, EMBASE, Cinahl, SportsDISCUS, Web of Science, and Scopus) were used. Included were human research studies in healthy sedentary adults, and healthy active adults, involving supplementation and control or placebo groups. Sedentary individuals with non-communicable disease risk or established gastrointestinal inflammatory or functional diseases/disorders were excluded. Results: A total of n = 1,204 participants were included from n = 37 papers reported resting outcomes, and n = 13 reported exercise-induced gastrointestinal syndrome (EIGS) outcomes. No supplement improved gastrointestinal permeability or gastrointestinal symptoms (GIS), and systemic endotoxemia at rest. Only modest positive changes in inflammatory cytokine profiles were observed in n = 3/15 studies at rest. Prebiotic studies (n = 4/5) reported significantly increased resting fecal Bifidobacteria, but no consistent differences in other microbes. Probiotic studies (n = 4/9) increased the supplemented bacterial species-strain. Only arabinoxylan oligosaccharide supplementation increased total fecal short chain fatty acid (SCFA) and butyrate concentrations. In response to exercise, probiotics did not substantially influence epithelial injury and permeability, systemic endotoxin profile, or GIS. Two studies reported reduced systemic inflammatory cytokine responses to exercise. Probiotic supplementation did not substantially influence GIS during exercise. Discussion: Synbiotic outcomes resembled probiotics, likely due to the minimal dose of prebiotic included. Methodological issues and high risk of bias were identified in several studies, using the Cochrane Risk of Bias Assessment Tool. A major limitation in the majority of included studies was the lack of a comprehensive approach of well-validated biomarkers specific to gastrointestinal outcomes and many included studies featured small sample sizes. Prebiotic supplementation can influence gut microbial composition and SCFA concentration; whereas probiotics increase the supplemented species-strain, with minimal effect on SCFA, and no effect on any other gastrointestinal status marker at rest. Probiotic and synbiotic supplementation does not substantially reduce epithelial injury and permeability, systemic endotoxin and inflammatory cytokine profiles, or GIS in response to acute exercise.

Plasma Endogenous Endotoxin Core Antibody Response to Exercise in Endurance Athletes.

The study aimed to investigate the impact of laboratory-controlled exertional and exertional-heat stress on concentrations of plasma endogenous endotoxin core antibody (EndoCAb). Forty-four (males n=26 and females n=18) endurance trained (V̇ O 2max 56.8min/kg/min) participants completed either: P1-2h high intensity interval running in 23°C ambient temperature (Tamb), P2-2h running at 60% V̇ O2max in 35°C Tamb, or P3-3h running at 60% V̇ O2max in 23°C Tamb. Blood samples were collected pre- and post-exercise to determine plasma IgM, IgA, and IgG concentrations. Overall resting pre-exercise levels for plasma Ig were 173MMU/ml, 37AMU/ml, and 79GMU/ml, respectively. Plasma IgM concentration did not substantially change pre- to post-exercise in all protocols, and the magnitude of pre- to post-exercise change for IgM was not different between protocols (p=0.135). Plasma IgA and IgG increased pre- to post-exercise in P2 only (p=0.017 and p=0.016, respectively), but remained within normative range (35-250MU/ml). P2 resulted in greater disturbances to plasma IgA (p=0.058) and IgG (p=0.037), compared with P1 and P3. No substantial differences in pre-exercise and exercise-associated change was observed for EndoCAb between biological sexes. Exertional and exertional-heat stress resulted in modest disturbances to systemic EndoCAb responses, suggesting EndoCAb biomarkers presents a low sensitivity response to controlled-laboratory experimental designs within exercise gastroenterology.

Gastrointestinal Assessment and Therapeutic Intervention for the Management of Exercise-Associated Gastrointestinal Symptoms: A Case Series Translational and Professional Practice Approach.

This translational research case series describes the implementation of a gastrointestinal assessment protocol during exercise (GastroAxEx) to inform individualised therapeutic intervention of endurance athletes affected by exercise-induced gastrointestinal syndrome (EIGS) and associated gastrointestinal symptoms (GIS). A four-phase approach was applied. Phase 1: Clinical assessment and exploring background history of exercise-associated gastrointestinal symptoms. Phase 2: Individual tailored GastroAxEx laboratory simulation designed to mirror exercise stress, highlighted in phase 1, that promotes EIGS and GIS during exercise. Phase 3: Individually programmed therapeutic intervention, based on the outcomes of Phase 2. Phase 4: Monitoring and readjustment of intervention based on outcomes from field testing under training and race conditions. Nine endurance athletes presenting with EIGS, and two control athletes not presenting with EIGS, completed Phase 2. Two athletes experienced significant thermoregulatory strain (peak core temperature attained > 40°C) during the GastroAxEx. Plasma cortisol increased substantially pre- to post-exercise in n = 6/7 (Δ > 500 nmol/L). Plasma I-FABP concentration increased substantially pre- to post-exercise in n = 2/8 (Δ > 1,000 pg/ml). No substantial change was observed in pre- to post-exercise for systemic endotoxin and inflammatory profiles in all athletes. Breath H2 responses showed that orocecal transit time (OCTT) was delayed in n = 5/9 (90-150 min post-exercise) athletes, with the remaining athletes (n = 4/9) showing no H2 turning point by 180 min post-exercise. Severe GIS during exercise was experienced in n = 5/9 athletes, of which n = 2/9 had to dramatically reduce work output or cease exercise. Based on each athlete's identified proposed causal factors of EIGS and GIS during exercise (i.e., n = 9/9 neuroendocrine-gastrointestinal pathway of EIGS), an individualised gastrointestinal therapeutic intervention was programmed and advised, adjusted from a standard EIGS prevention and management template that included established strategies with evidence of attenuating EIGS primary causal pathways, exacerbation factors, and GIS during exercise. All participants reported qualitative data on their progress, which included their previously presenting GIS during exercise, such as nausea and vomiting, either being eliminated or diminished resulting in work output improving (i.e., completing competition and/or not slowing down during training or competition as a result of GIS during exercise). These outcomes suggest GIS during exercise in endurance athletes are predominantly related to gastrointestinal functional and feeding tolerance issues, and not necessarily gastrointestinal integrity and/or systemic issues. GastroAxEx allows for informed identification of potential causal pathway(s) and exacerbation factor(s) of EIGS and GIS during exercise at an individual level, providing a valuable informed individualised therapeutic intervention approach.

Feeding Tolerance, Glucose Availability, and Whole-Body Total Carbohydrate and Fat Oxidation in Male Endurance and Ultra-Endurance Runners in Response to Prolonged Exercise, Consuming a Habitual Mixed Macronutrient Diet and Carbohydrate Feeding During Exercise.

Using metadata from previously published research, this investigation sought to explore: (1) whole-body total carbohydrate and fat oxidation rates of endurance (e.g., half and full marathon) and ultra-endurance runners during an incremental exercise test to volitional exhaustion and steady-state exercise while consuming a mixed macronutrient diet and consuming carbohydrate during steady-state running and (2) feeding tolerance and glucose availability while consuming different carbohydrate regimes during steady-state running. Competitively trained male endurance and ultra-endurance runners (n = 28) consuming a balanced macronutrient diet (57 ± 6% carbohydrate, 21 ± 16% protein, and 22 ± 9% fat) performed an incremental exercise test to exhaustion and one of three 3 h steady-state running protocols involving a carbohydrate feeding regime (76-90 g/h). Indirect calorimetry was used to determine maximum fat oxidation (MFO) in the incremental exercise and carbohydrate and fat oxidation rates during steady-state running. Gastrointestinal symptoms (GIS), breath hydrogen (H2), and blood glucose responses were measured throughout the steady-state running protocols. Despite high variability between participants, high rates of MFO [mean (range): 0.66 (0.22-1.89) g/min], Fatmax [63 (40-94) % V̇O2max], and Fatmin [94 (77-100) % V̇O2max] were observed in the majority of participants in response to the incremental exercise test to volitional exhaustion. Whole-body total fat oxidation rate was 0.8 ± 0.3 g/min at the end of steady-state exercise, with 43% of participants presenting rates of ≥1.0 g/min, despite the state of hyperglycemia above resting homeostatic range [mean (95%CI): 6.9 (6.7-7.2) mmol/L]. In response to the carbohydrate feeding interventions of 90 g/h 2:1 glucose-fructose formulation, 38% of participants showed breath H2 responses indicative of carbohydrate malabsorption. Greater gastrointestinal symptom severity and feeding intolerance was observed with higher carbohydrate intakes (90 vs. 76 g/h) during steady-state exercise and was greatest when high exercise intensity was performed (i.e., performance test). Endurance and ultra-endurance runners can attain relatively high rates of whole-body fat oxidation during exercise in a post-prandial state and with carbohydrate provisions during exercise, despite consuming a mixed macronutrient diet. Higher carbohydrate intake during exercise may lead to greater gastrointestinal symptom severity and feeding intolerance.

Diurnal versus Nocturnal Exercise-Effect on the Gastrointestinal Tract.

PURPOSE: The study aimed to determine the effect of diurnal versus nocturnal exercise on gastrointestinal integrity and functional responses, plasma lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) concentrations (as indirect indicators of endotoxin responses), systemic inflammatory cytokine profile, gastrointestinal symptoms, and feeding tolerance. METHODS: Endurance runners (n = 16) completed 3 h of 60% V˙O2max (22.7°C, 45% relative humidity) running, on one occasion performed at 0900 h (400 lx; DAY) and on another occasion at 2100 h (2 lx; NIGHT). Blood samples were collected pre- and postexercise and during recovery to determine plasma concentrations of cortisol, catecholamines, claudin-3, I-FABP, LBP, and sCD14 and inflammatory cytokine profiles by ELISA. Orocecal transit time (OCTT) was determined by lactulose challenge test given at 150 min, with concomitant breath hydrogen (H2) and gastrointestinal symptom determination. RESULTS: Cortisol increased substantially pre- to postexercise on NIGHT (+182%) versus DAY (+4%) (trial-time, P = 0.046), with no epinephrine (+41%) and norepinephrine (+102%) trial differences. I-FABP, but not claudin-3, increased pre- to postexercise on both trials (mean = 2269 pg·mL-1, 95% confidence interval = 1351-3187, +143%) (main effect of time [MEOT], P < 0.001). sCD14 increased pre- to postexercise (trial-time, P = 0.045, +5.6%) and was greater on DAY, but LBP decreased (MEOT, P = 0.019, -11.2%) on both trials. No trial difference was observed for systemic cytokine profile (MEOT, P = 0.004). Breath H2 responses (P = 0.019) showed that OCTT was significantly delayed on NIGHT (>84 min, with n = 3 showing no breath H2 turning point by 180 min postexercise) compared with DAY (mean = 54 min, 95% confidence interval = 29-79). NIGHT resulted in greater total gastrointestinal symptoms (P = 0.009) compared with DAY. No difference in feeding tolerance markers was observed between trials. CONCLUSION: Nocturnal exercise instigates greater gastrointestinal functional perturbations and symptoms compared with diurnal exercise. However, there are no circadian differences to gastrointestinal integrity and systemic perturbations in response to the same exertional stress and controlled procedures.

Gut-training: the impact of two weeks repetitive gut-challenge during exercise on gastrointestinal status, glucose availability, fuel kinetics, and running performance.

Due to gastrointestinal tract adaptability, the study aimed to determine the impact of gut-training protocol over 2 weeks on gastrointestinal status, blood glucose availability, fuel kinetics, and running performance. Endurance runners (n = 25) performed a gut-challenge trial (GC1), consisting of 2 h running exercise at 60% V̇O2max whilst consuming gel-discs containing 30 g carbohydrates (2:1 glucose/fructose, 10% w/v) every 20 min and a 1 h distance test. Participants were then randomly assigned to a carbohydrate gel-disc (CHO-S), carbohydrate food (CHO-F), or placebo (PLA) gut-training group for 2 weeks of repetitive gut-challenge intervention. Participants then repeated a second gut-challenge trial (GC2). Gastrointestinal symptoms reduced in GC2 on CHO-S (60%; p = 0.008) and CHO-F (63%; p = 0.046); reductions were greater than PLA (p < 0.05). H2 peak was lower in GC2 on CHO-S (mean (CI): 6 (4-8) ppm) compared with CHO-F (9 (6-12) ppm) and PLA (12 (2-21) ppm) (trial × time: p < 0.001). Blood glucose concentration was higher in GC2 on CHO-S (7.2 (6.3-8.1) mmol·L-1) compared with CHO-F (6.1 (5.7-6.5) mmol·L-1) and PLA (6.2 (4.9-7.5) mmol·L-1) (trial × time: p = 0.015). No difference in oxidation rates, plasma I-FABP, and cortisol concentrations were observed between groups and trials. Distance test improved on CHO-S (5.2%) and CHO-F (4.3%) in GC2, but not on PLA (-2.1%) (trial × time: p = 0.009). Two weeks of gut-training with CHO-S and CHO-F improved gastrointestinal symptoms and running performance compared with PLA. CHO-S also reduced malabsorption and increased blood glucose availability during endurance running compared with PLA.