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Sucralose and acesulfame-potassium consumption alters gut microbiota in rodents, with unclear effects in humans. We examined effects of three-times daily sucralose- and acesulfame-potassium-containing diet soda consumption for 1 (n = 17) or 8 (n = 8) weeks on gut microbiota composition in young adults. After 8 weeks of diet soda consumption, the relative abundance of Proteobacteria, specifically Enterobacteriaceae, increased; and, increased abundance of two Proteobacteria taxa was also observed after 1 week of diet soda consumption compared with sparkling water. In addition, three taxa in the Bacteroides genus increased following 1 week of diet soda consumption compared with sparkling water. The clinical relevance of these findings and effects of sucralose and acesulfame-potassium consumption on human gut microbiota warrant further investigation in larger studies. Clinical trial registration: NCT02877186 and NCT03125356. [ABSTRACT FROM AUTHOR]