AIM To determine if 30-d of oral spore-based probiotic supplementation could reduce dietary endotoxemia. METHODS Apparently healthy men and women(n = 75) were screened for post-prandial dietary endotoxemia. Subjects whose serum endotoxin concentration increased by at least 5-fold from pre-meal levels at 5-h post-prandial were considered “responders” and were randomized to receive either placebo(rice flour) or a commercial sporebased probiotic supplement [Bacillus indicus(HU36), Bacillus subtilis(HU58), Bacillus coagulans, and Bacillus licheniformis, and Bacillus clausii] for 30-d. The dietary endotoxemia test was repeated at the conclusion of the supplementation period. Dietary endotoxin(LAL) and triglycerides(enzymatic) were measured using an automated chemistry analyzer. Serum disease risk biomarkers were measured using bead-based multiplex assays(Luminex and Milliplex) as secondary, exploratory measures. RESULTS Data were statistically analyzed using repeated measures ANOVA and a P < 0.05. We found that spore-based probiotic supplementation was associated with a 42% reduction in endotoxin(12.9 ± 3.5 vs 6.1 ± 2.6, P = 0.011) and 24% reduction in triglyceride(212 ± 28 vs 138 ± 12, P = 0.004) in the post-prandial period Placebo subjects presented with a 36% increase in endotoxin(10.3 ± 3.4 vs 15.4 ± 4.1, P = 0.011) and 5% decrease in triglycerides(191 ± 24 vs 186 ± 28, P = 0.004) over the same post-prandial period. We also found that sporebased probiotic supplementation was associated with significant post-prandial reductions in IL-12p70(24.3 ± 2.2 vs 21.5 ± 1.7, P = 0.017) and IL-1β(1.9 ± 0.2 vs 1.6 ± 0.1, P = 0.020). Compared to placebo post supplementation, probiotic subject had less ghrelin(6.8 ± 0.4 vs 8.3 ± 1.1, P = 0.017) compared to placebo subjects. CONCLUSION The key findings of the present study is that oral sporebased probiotic supplementation reduced symptoms indicative of “leaky gut syndrome”. AIM To determine if 30-d of oral spore-based probiotic supplementation could reduce dietary endotoxemia. METHODS Apparently healthy men and women (n = 75) were screened for post-prandial dietary endotoxemia. Subjects whose serum endotoxin concentration increased by at least 5- fold from pre-meal levels at 5-h post-prandial were considered “responders ” and were randomized to receive either placebo (rice flour) or a commercial sporebased probiotic supplement [Bacillus indicus (HU36), Bacillus subtilis Bacillus coagulans, and Bacillus licheniformis, and Bacillus clausii] for 30-d. The dietary endotoxemia test was repeated at the conclusion of the supplementation period. Dietary endotoxin (LAL) and triglycerides (enzymatic) were measured using an automated chemistry analyzer. risk biomarkers were measured using bead-based multiplex assays (Luminex and Milliplex) as secondary, exploratory measures. RESULTS Data were analyzed used using repeated measures ANOVA and a P <0.05. We found that spore-based probiotic supplementation was associated with a 42% reduction in endotoxin (12.9 ± 3.5 vs 6.1 ± 2.6, P = 0.011) and 24% reduction in triglyceride (212 ± 28 vs 138 ± 12, P = 0.004) in the post-prandial period Placebo subjects presented with a 36% increase in endotoxin (10.3 ± 3.4 vs 15.4 ± 4.1, P = 0.011) and 5% decrease in triglycerides (191 ± 24 vs 186 ± 28, P = 0.004) ) over the same post-prandial period. We also found that spore-based probiotic supplementation was associated with significant post-prandial reductions in IL-12p70 (24.3 ± 2.2 vs 21.5 ± 1.7, P = 0.017) and IL- 1.6 ± 0.1, P = 0.020). Compared to placebo post supplementation, probiotic subjects had less ghrelin (6.8 ± 0.4 vs. 8.3 ± 1.1, P = 0.017) compared to placebo subjects. CONCLUSION The key findings of the present study is that oral sporebased probiotic supplementation reduced symptoms indicative of “leaky gut syndrome ”.