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Widespread use of probiotics and the presence of these microorganisms in human food-chain, established an argument against the safety profile of probiotics. Various case-reports, clinical trials and experimental studies have been mentioned different types of side-effects induced by the consumption of probiotics. Although previous studies reported beneficial impacts in alleviating the gastrointestinal (GI) problems, cardiovascular disorders and metabolic syndromes, the most at-risk groups of populations such as pediatrics, geriatrics, critically-ill patients are at higher risks of the occurrence of some life-threatening or life-lasting adverse events. Bacteremia, fungemia, GI disorders, metabolic problems, extreme immune stimulations, seizure, Kawasaki disease and etc. have been associated with the use of probiotics. Moreover, due to the antibiotic resistance gene reservoir property of the GI tract, transference of the resistance genes among probiotics, human normal flora and pathogenic microorganisms endow probiotics to propagate antibiotic resistance genes globally.