Prolonged exercise, particularly in the heat, results in gastrointestinal hypoperfusion and oxidative damage, compromising gastrointestinal tight junction proteins and intestinal mucosa wall integrity, increasing epithelial permeability and the potential for translocation of luminal endotoxins into the circulation. The aim of this thesis was to determine the effects of exercise intensity and duration, coupled with environmental heat stress, as well as short-term nutritional interventions, on blood markers of gastrointestinal damage and immune/inflammatory response in well-trained and elite athletes. A systematic review evaluated the effects of exercise in the heat on blood markers of gastrointestinal epithelial disturbance in well-trained individuals (Chapter 3). The findings of the review indicate that prolonged high-intensity (>70% 𝑉̇O2max) exercise in the heat acutely increases biomarkers of gastrointestinal permeability (e.g. lipopolysaccharide endotoxin [LPS]) and damage (e.g. IFABP, sCD14) compared to exercise in cooler conditions. The first experimental study (Chapter 4) found that treadmill running at increasing intensities (i.e. 60, 75 and 95% 𝑉̇O2max) led to transient perturbations in gastrointestinal permeability in well-trained athletes, as indicated by a 69% increase (0.2 EU·mL-1, 0.1 to 0.4; P=0.011) in LPS, irrespective of exercising in hot (34°C, 68% RH) or cool (18°C, 57% RH) conditions. However, LPS binding protein (LBP) was 4% (5.3 μg·mL-1, 2.4 to 8.4; P<0.001), 32% (4.6 μg·mL-1, 1.8 to 7.4; P=0.002) and 30% (3.0 μg·mL-1, 0.03 to 5.9; P=0.047) higher in the hot condition following exercise at 60%, 75% and 95% 𝑉̇O2max, respectively, compared to the cooler condition. Moreover, intestinal fatty acid binding protein (IFABP) was 43% (2.1 ng·mL-1, 0.1 to 4.2; P=0.04) higher 1h post-exercise in the hot compared to the cool condition. Self-reported gastrointestinal discomfort between the HOT and COOL conditions did not differ (P=0.597). These data suggest that running at increasing intensities in the heat resulted in acute but transient changes in gastrointestinal perturbations, which were well-tolerated by the endurance-trained cohort, as indicated by the lack of reported gastrointestinal discomfort (i.e. symptoms). In the second experimental study (Chapter 5), non-heat acclimated male team-sport athletes completed a 5-session, repeated-sprint training regimen over seven days in either HOT (40°C and 40% RH) or COOL (20°C and 40% RH) conditions. In the heat, IFABP increased by 593 pg·mL-1 (254 to 932 pg·mL-1; 95% CI; P<0.001) immediately post-exercise and was 454 pg·mL-1 (115 to 793 pg·mL-1; P<0.004) higher 1 h post-exercise, relative to baseline. Soluble CD14 (sCD14) increased by 398 ng·mL-1 (149 to 647 ng·mL-1; P=0.001) following exercise in the heat compared to the cool condition on Day 1 and by 308 ng·mL-1 (59 to 557 ng·mL-1; P=0.010) on Day 5. LBP increased by 1694 ng·mL-1 (424 to 2964 ng·mL-1; P=0.005) immediately post-exercise in the heat on Day 1 and remained unchanged in the cooler condition. These findings indicated that exercise under heat stress, rather than exercise alone, exacerbates gastrointestinal disturbances and immune activation when performing maximal repeated-sprint efforts. Finally, the third experimental study (Chapter 6) compared the effects of short-term (i.e. five days) low carbohydrate high fat (LCHF) and high carbohydrate (HCHO) dietary interventions on blood markers of gastrointestinal damage during a 25-km race walk in warm conditions in elite athletes. The results showed that the LCHF diet increased IFABP concentration by 1822 pg·mL-1 (1205 to 2438; P<0.001) and 662 pg·mL-1 (160 to 1163; P=0.010) post and 1 h post 25-km race walk, relative to the HCHO diet. sCD14 was 0.9 μg·mL-1 (0.2 to 1.7; P=0.013) higher pre-exercise, 1.9 μg·mL-1 (1.2 to 2.6; P<0.001) higher post-exercise, and 2.5 μg·mL-1 (1.8 to 3.2; P<0.001) higher 1 h post-exercise after consuming the LCHF diet, compared to HCHO diet. Interleukin (IL)-1Ra increased by 57.5 pg·mL-1 (23.8 to 91.1; P<0.001) and 84.7 pg·mL-1 (51.0 to 118.4; P<0.001) post- and 1 h post-exercise, and IL-10 increased by 77.5 pg·mL-1 (59.2 to 95.9; P<0.001) and 83.4 pg·mL-1 (65.1 to 101.8; P<0.001) post- and 1 h post-exercise in LCHF diet. While IFABP is commonly used as a marker of gastrointestinal damage, its greater concentration in the blood following the LCHF diet suggests that it may have a protective function in cells under metabolic stress, and therefore represent a marker of increased lipid intake and oxidation. Furthermore, the increased cytokines (i.e. IL-1Ra, IL-10) may suggest a regulatory macrophage response in the LCHF group. The results of this thesis suggest that: 1) well-trained and elite athletes experience transient perturbations in blood markers of gastrointestinal damage when exercising in the heat; 2) maximal repeated-sprint exercise in the heat acutely increases gastrointestinal damage and immune activation compared to sprinting in the cool; and 3) LCHF diets increase IFABP concentration, which is typically indicative of gastrointestinal damage, however, may also act as a marker of increased lipid intake and alter the systemic immune inflammatory response to strenuous exercise in elite athletes. Furthermore, it appears that most of the current research is focused on healthy or trained individuals, leaving a gap in knowledge regarding the acute and chronic responses of well-trained and elite populations. Therefore, further investigation is required to determine whether well-trained individuals have an enhanced capacity to overcome gastrointestinal disturbances during exercise in the heat compared to untrained individuals.