Exertional Stress-induced Pathogenic Luminal Content Translocation - Friend or Foe?

The incidence of perturbed gastrointestinal integrity, as well as resulting systemic immune responses and gastrointestinal symptoms, otherwise known as exercised-induced gastrointestinal syndrome (EIGS), is common among individuals who partake in prolonged exercise. EIGS may cause the translocation of pathogenic material, including whole bacteria and bacterial endotoxins, from the lumen into circulation, which may progress into clinical consequences such as sepsis, and potentially subsequent fatality. However, further investigation is warranted to assess the possibility of food allergen and/or digestive enzyme luminal to circulatory translocation in response to exercise, and the clinical consequences. Findings from this narrative literature review demonstrate evidence that whole bacteria and bacterial endotoxins translocation from the gastrointestinal lumen to systemic circulation occurs in response to exercise stress, with a greater propensity of translocation occurring with accompanying heat exposure. It has also been demonstrated that food allergens can translocate from the lumen to systemic circulation in response to exercise stress and initiate anaphylaxis. To date, no research investigating the effect of exercise on the translocation of digestive enzymes from the lumen into systemic circulation exists. It is evident that EIGS and consequential pathogenic translocation presents life-threatening clinical implications, warranting the development and implementation of effective management strategies in at-risk populations.

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.

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 a 24-h Low and High Fermentable Oligo- Di- Mono-Saccharides and Polyol (FODMAP) Diet on Plasma Bacterial Profile in Response to Exertional-Heat Stress.

Exertional-heat stress (EHS) compromises intestinal epithelial integrity, potentially leading to the translocation of pathogenic agents into circulation. This study aimed to explore the impact of EHS on the systemic circulatory bacterial profile and to determine the impact of a short-term low (LFOD) and high (HFOD) fermentable oligo- di- mono-saccharide and polyol dietary intervention before EHS on this profile. Using a double-blind randomized cross-over design, thirteen endurance runners (n = 8 males, n = 5 females), with a history of exercise-associated gastrointestinal symptoms (Ex-GIS), consumed a 24 h LFOD and HFOD before 2 h running at 60% V.O2max in 35.6 °C. Blood and fecal samples were collected pre-EHS to determine plasma microbial DNA concentration, and sample bacteria and short chain fatty acid (SCFA) profiles by fluorometer quantification, 16S rRNA amplicon gene sequencing, and gas chromatography, respectively. Blood samples were also collected post-EHS to determine changes in plasma bacteria. EHS increased plasma microbial DNA similarly in both FODMAP trials (0.019 ng·µL-1 to 0.082 ng·µL-1) (p < 0.01). Similar pre- to post-EHS increases in plasma Proteobacteria (+1.6%) and Firmicutes (+0.6%) phyla relative abundance were observed in both FODMAP trials. This included increases in several Proteobacteria genus (Delftia and Serratia) groups. LFOD presented higher fecal Firmicutes (74%) and lower Bacteroidota (10%) relative abundance pre-EHS, as a result of an increase in Ruminococcaceae and Lachnospiraceae family and respective genus groups, compared with HFOD (64% and 25%, respectively). Pre-EHS plasma total SCFA (p = 0.040) and acetate (p = 0.036) concentrations were higher for HFOD (188 and 178 µmol·L-1, respectively) vs. LFOD (163 and 153 µmol·L-1, respectively). Pre-EHS total fecal SCFA concentration (119 and 74 µmol·g-1; p < 0.001), including acetate (74 and 45 µmol·g-1; p = 0.001), butyrate (22 and 13 µmol·g-1; p = 0.002), and propionate (20 and 13 µmol·g-1; p = 0.011), were higher on HFOD vs LFOD, respectively. EHS causes the translocation of whole bacteria into systemic circulation and alterations to the plasma bacterial profile, but the FODMAP content of a 24 h diet beforehand does not alter this outcome.