Assessment of Exercise-Associated Gastrointestinal Perturbations in Research and Practical Settings: Methodological Concerns and Recommendations for Best Practice.

Strenuous exercise is synonymous with disturbing gastrointestinal integrity and function, subsequently prompting systemic immune responses and exercise-associated gastrointestinal symptoms, a condition established as "exercise-induced gastrointestinal syndrome." When exercise stress and aligned exacerbation factors (i.e., extrinsic and intrinsic) are of substantial magnitude, these exercise-associated gastrointestinal perturbations can cause performance decrements and health implications of clinical significance. This potentially explains the exponential growth in exploratory, mechanistic, and interventional research in exercise gastroenterology to understand, accurately measure and interpret, and prevent or attenuate the performance debilitating and health consequences of exercise-induced gastrointestinal syndrome. Considering the recent advancement in exercise gastroenterology research, it has been highlighted that published literature in the area is consistently affected by substantial experimental limitations that may affect the accuracy of translating study outcomes into practical application/s and/or design of future research. This perspective methodological review attempts to highlight these concerns and provides guidance to improve the validity, reliability, and robustness of the next generation of exercise gastroenterology research. These methodological concerns include participant screening and description, exertional and exertional heat stress load, dietary control, hydration status, food and fluid provisions, circadian variation, biological sex differences, comprehensive assessment of established markers of exercise-induced gastrointestinal syndrome, validity of gastrointestinal symptoms assessment tool, and data reporting and presentation. Standardized experimental procedures are needed for the accurate interpretation of research findings, avoiding misinterpreted (e.g., pathological relevance of response magnitude) and overstated conclusions (e.g., clinical and practical relevance of intervention research outcomes), which will support more accurate translation into safe practice guidelines.

Psyllium reduces inulin-induced colonic gas production in IBS: MRI and in vitro fermentation studies.

OBJECTIVE: Health-promoting dietary fibre including inulin often triggers gastrointestinal symptoms in patients with IBS, limiting their intake. Our aim was to test if coadministering psyllium with inulin would reduce gas production. DESIGN: A randomised, four-period, four-treatment, placebo-controlled, crossover trial in 19 patients with IBS. Subjects ingested a 500 mL test drink containing either inulin 20 g, psyllium 20 g, inulin 20 g+ psyllium 20 g or dextrose 20 g (placebo). Breath hydrogen was measured every 30 min with MRI scans hourly for 6 hours. Faecal samples from a subset of the patients with IBS were tested using an in vitro fermentation model. Primary endpoint was colonic gas assessed by MRI. RESULTS: Colonic gas rose steadily from 0 to 6 hours, with inulin causing the greatest rise, median (IQR) AUC(0-360 min) 3145 (848-6502) mL·min. This was significantly reduced with inulin and psyllium coadministration to 618 (62-2345) mL·min (p=0.02), not significantly different from placebo. Colonic volumes AUC(0-360 min) were significantly larger than placebo for both inulin (p=0.002) and inulin and psyllium coadministration (p=0.005). Breath hydrogen rose significantly from 120 min after inulin but not psyllium; coadministration of psyllium with inulin delayed and reduced the maximum increase, AUC(0-360 min) from 7230 (3255-17910) ppm·hour to 1035 (360-4320) ppm·hour, p=0.007.Fermentation in vitro produced more gas with inulin than psyllium. Combining psyllium with inulin did not reduce gas production. CONCLUSIONS: Psyllium reduced inulin-related gas production in patients with IBS but does not directly inhibit fermentation. Whether coadministration with psyllium increases the tolerability of prebiotics in IBS warrants further study. TRIAL REGISTRATION NUMBER: NCT03265002.

Dietary fibre in gastrointestinal health and disease.

Epidemiological studies have consistently demonstrated the benefits of dietary fibre on gastrointestinal health through consumption of unrefined whole foods, such as wholegrains, legumes, vegetables and fruits. Mechanistic studies and clinical trials on isolated and extracted fibres have demonstrated promising regulatory effects on the gut (for example, digestion and absorption, transit time, stool formation) and microbial effects (changes in gut microbiota composition and fermentation metabolites) that have important implications for gastrointestinal disorders. In this Review, we detail the major physicochemical properties and functional characteristics of dietary fibres, the importance of dietary fibres and current evidence for their use in the management of gastrointestinal disorders. It is now well-established that the physicochemical properties of different dietary fibres (such as solubility, viscosity and fermentability) vary greatly depending on their origin and processing and are important determinants of their functional characteristics and clinical utility. Although progress in understanding these relationships has uncovered potential therapeutic opportunities for dietary fibres, many clinical questions remain unanswered such as clarity on the optimal dose, type and source of fibre required in both the management of clinical symptoms and the prevention of gastrointestinal disorders. The use of novel fibres and/or the co-administration of fibres is an additional therapeutic approach yet to be extensively investigated.

Nutrient, fibre, sorbitol and chlorogenic acid content of prunes (Prunus domestica): an updated analysis and comparison of different countries of origin and database values.

Current prune composition data are outdated and require a comprehensive and comparative re-analysis. This novel study aimed to: (i) analyse and compare prune composition from major countries of origin; and (ii) provide a comprehensive compositional analysis of prunes of USA origin and compare this with UK and USA database data. Prune samples were analysed for major nutrients and bioactive compounds and compared between countries of origin. Total fibre was higher in prunes from the USA (12.0 g/100 g) and Chile (11.5 g/100 g) compared with France (8.4 g/100 g) and Argentina (8.9 g/100 g), while prunes from all countries contained high levels of sorbitol (11.2-15.5 g/100 g). Differences in energy and starch values compared with national databases reflected different approaches to sampling and analysis. In conclusion, prunes contain high levels of fibre and other bioactive compounds. Variations between country of origin and database values highlight the importance of transparency in documenting sampling and analysis methods.

Measurement of saliva flow rate in healthy young humans: influence of collection time and mouthrinse water temperature.

The aim of the current study was to determine if unstimulated saliva flow (measured in µl min-1 ) is affected by different durations of sample collection and by temperatures of mouthrinse water used before sample collection. In randomized order, participants provided 10 samples of unstimulated saliva at time points ranging from 1 to 6 min after rinsing with different temperatures of water (10, 20, and 30°C). Data were analysed by one-way anova with post-hoc tests. Test-retest reliability was assessed using Bland-Altman plots and correlation coefficients. A larger volume of saliva was obtained over a longer collection time. No significant difference in saliva flow rate was observed between collection times [mean: 364 (95% CI: 332-397) µl min-1 ]. Although rinsing with different temperatures of mouthrinse water resulted in no significant difference in saliva flow rates as a result of the mouthrinse water temperatures, 60% of the participants had a higher saliva flow rate after rinsing with mouthrinse water at a temperature of 10°C compared with mouthrinse water at 20 and 30°C, suggesting large individual variation (range: 24-420 µl min-1 ). These findings provide justification for using saliva collection times of 1-6 min during sampling of unstimulated saliva. The large individual variations in saliva flow rate in response to different mouthrinse water temperatures suggest that standardization, control, and reporting of mouthrinse water temperature is warranted.

Does Short-Term High Dose Probiotic Supplementation Containing Lactobacillus casei Attenuate Exertional-Heat Stress Induced Endotoxaemia and Cytokinaemia?

The study aimed to determine if short-term high dose probiotic supplementation containing Lactobacillus casei (L.casei) attenuates the commonly reported exertional-heat stress (EHS) induced endotoxinaemia and cytokinaemia. Eight endurance trained male volunteers (mean± SD: age 26 ± 6 y, nude body mass 70.2 ± 8.8 kg, height 1.75 ± 0.05 m, VO2max 59 ± 5 ml·kg-1·min-1) completed a blinded randomized cross-over design, whereby oral ingestion of a commercially available probiotic beverage containing L.casei (volume equivalent for ×1011 colony forming units·day-1) (PRO) or placebo (PLA) was consumed for 7 consecutive days before exposure to EHS, which comprised of 2h running exercise at 60% VO2max in hot ambient conditions (34.0 °C and 32% RH). Blood samples were collected at baseline (7 days before EHS), pre-EHS, post-EHS (1 hr, 2 hr, 4 hr, and at 24 hr). Plasma samples were analyzed for gram-negative bacterial endotoxin, cytokine profile (IL-6, IL-1ß, TNF-α, IFN-γ, IL-8, and IL-10) and plasma osmolality. Plasma osmolality did not differ between trials. Seven days of L.casei supplementation did not show significant changes in resting circulatory endotoxin concentration or plasma cytokine profile compared with PLA. A main effect of time was observed for IL-6, TNF-α, IL-10 and IL-8; whereby levels increased in response to EHS (p < .05). Relative to pre-EHS concentrations, higher plasma concentrations of endotoxin (p = .05), and a trend for higher plasma TNF-α concentration (p = .09) was observed on PRO compared with PLA throughout recovery. Short-term high dose supplementation of a probiotic beverage containing L.casei before EHS did not attenuate EHS induced endotoxaemia and cytokinaemia; nor is it more positively favorable over a placebo.

Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition.

Exertional-heat stress has the potential to disturb intestinal integrity, leading to enhanced permeability of enteric pathogenic micro-organisms and associated clinical manifestations. The study aimed to determine the circulatory endotoxin concentration and cytokine profile of ultra-endurance runners (UER, n=19) and a control group (CON, n=12) during a five stage 230km ultra-marathon (mean ± SD: 27h38min ± 3h55min) conducted in hot and dry environmental conditions (30ºC to 40ºC and 31% to 40% relative humidity). Body mass and tympanic temperature were measured, and venous blood samples were taken before (pre-stage) and immediately after (post-stage) each stage of the ultra-marathon for the analysis of gram-negative bacterial endotoxin, C-reactive protein, cytokine profile (IL-6, IL-1ß, TNF-α, IFN-γ, IL-10, and IL- 1ra), and plasma osmolality. Gastrointestinal symptoms and perceptive thermal tolerance rating were also monitored throughout competition. Mean exercise-induced body mass loss over the five stages ranged 1.0% to 2.5%. Pre- and poststage plasma osmolality in UER ranged277 to 282mOsmol/kg and 286 to 297 mOsmol/kg, respectively. Pre-stage concentrations of endotoxin (peak: 21% at Stage 5), C-reactive protein (889% at Stage 3), IL-6 (152% at Stage 2), IL-1ß (95% at Stage 5), TNF-α (168% at Stage 5), IFN-γ (102% at Stage 5),IL-10 (1271% at Stage 3), and IL-1ra (106% at Stage 5) increased as the ultra-marathon progressed in UER; while no changes in CON were observed (except for IL-1ß, 71% at Stage 5). Pre- to post-stage increases were observed for endotoxin (peak: 22% at Stage 3), C-reactive protein (25% at Stage 1), IL-6 (238% at Stage 1), IL-1ß (64% at Stage 1), TNF-α (101% at Stage 1), IFN-γ (39% at Stage 1), IL-10 (1100% at Stage 1), and IL-1ra(207% at Stage 1) concentrations in UER. Multi-stage ultra-marathon competition in the heat resulted in a modest circulatory endotoxaemia accompanied by a pronounced pro-inflammatory cytokinaemia by post-Stage 1, both of which were sustained throughout competition at rest (pre-stage) and after stage completion. Compensatory anti-inflammatory responses and other external factors (i.e., training status, cooling strategies, heat acclimatization, nutrition and hydration) may have contributed towards limiting the extent of pro-inflammatory responses in the current scenario.

Perturbed energy balance and hydration status in ultra-endurance runners during a 24 h ultra-marathon.

The present study aimed to assess the adequacy of energy, macronutrients and water intakes of ultra-endurance runners (UER) competing in a 24 h ultra-marathon (distance range: 122-208 km). The ad libitum food and fluid intakes of the UER (n 25) were recorded throughout the competition and analysed using dietary analysis software. Body mass (BM), urinary ketone presence, plasma osmolality (POsmol) and volume change were determined at pre- and post-competition time points. Data were analysed using appropriate t tests, with significance set at P <0·05. The total energy intake and expenditure of the UER were 20 (sd 12) and 55 (sd 11) MJ, respectively (control (CON) (n 17): 12 (sd 1) and 14 (sd 5) MJ, respectively). The protein, carbohydrate and fat intakes of the UER were 1·1 (sd 0·4), 11·3 (sd 7·0) and 1·5 (sd 0·7) g/kg BM, respectively. The rate of carbohydrate intake during the competition was 37 (sd 24) g/h. The total water intake of the UER was 9·1 (sd 4·0) litres (CON: 2·1 (sd 1·0) litres), while the rate of water intake was 378 (sd 164) ml/h. Significant BM loss occurred at pre- to post-competition time points (P =0·001) in the UER (1·6 (sd 2·0) %). No significant changes in POsmol values were observed at pre- (285 (sd 11) mOsmol/kg) to post-competition (287 (sd 10) mOsmol/kg) time points in the UER and were lower than those recorded in the CON group (P <0·05). However, plasma volume (PV) increased at post-competition time points in the UER (10·2 (sd 9·7) %; P <0·001). Urinary ketones were evident in the post-competition samples of 90 % of the UER. Energy deficit was observed in all the UER, with only one UER achieving the benchmark recommendations for carbohydrate intake during endurance exercise. Despite the relatively low water intake rates recorded in the UER, hypohydration does not appear to be an issue, considering increases in PV values observed in the majority (80 %) of the UER. Population-specific dietary recommendations may be beneficial and warranted.