Table 4.

Studies evaluating the effect of sucralose on the gut microbiota.

REFERENCE	SPECIES	DOSE OF SUCRALOSE AND EXPOSURE	OUTCOMES	CLINICAL OUTCOMES
Bian et al., 2017 [72]	Male mice	5 mg/kg b.w./day for 3 or 6 months	at 3 months: ↑ Ruminococcus; ↓ Lachnospiraceae, Dehalobacteriaceae, Anaerostipes, Staphylococcus, Peptostreptococcaceae, Bacillus at 6 months: ↑ Akkermansia, Turicibacter, Roseburia, Clostridiaceae, Christensenellaceae; ↓ Streptococcus, Lachnospiraceae, Dehalobacteriaceae, Erysipelotrichaceae	at 3 months: Not reported at 6 months: Increase in genes related to bacterial pro-inflammatory mediators in sucralose-treated mice (p < 0.01). Hepatic increase in the gene expression of pro-inflammatory markers, (p < 0.05).
Uebanso et al., 2017 [106]	Male mice	15 mg/kg b.w./day for 8 weeks	↓ relative amount of Clostridium cluster XIVa in the fecal microbiota	Increase in hepatic cholesterol and cholic acid.
Rodriguez-Palacios et al., 2018 [112]	SAMP1/YitFc mice	3.5 mg/mL of Splenda® (sucralose maltodextrin, 1:99, w/w) in the drinking water for 6 weeks	↑ 5 microbial classes within the Proteobacteria phylum (Alphaproteobacteria, Betaproteobacteria, Epsilonproteobacteria, Deltaproteobacteria, and Gammaproteobacteria). ↑Escherichia coli in fecal microbiota	Possible exacerbation of myeloperoxidase and intestinal reactivity in mice with a pro-inflammatory predisposition but not in healthy animals.
Wang et al., 2018 [113]	5-week-old Mice	~3.3 mg/kg b.w./day + standard diet ~1.5 mg/kg b.w./day + high-fat diet	↑ Firmicutes ↑ Further increase of Firmicutes	Body weight loss in mice fed a standard (p < 0.0001), but not a high-fat diet (p = 0.1250) in the absence of differences in food intake, calorie intake, or water intake.
Stichelen et al., 2019 [107]	Pregnant mice	Sucralose + 0.1 or 0.2 mg Acesulfame-K for 6 weeks	↑ Firmicutes in the gut microbiota of offspring ↓ Akkermansia muciniphila in the gut microbiota of offspring	A total of 0.2 mg of sucralose and 0.5 mg of acesulfame-K lowered the pups’ weight (p < 0.0001) and fasting glucose (p < 0.05) vs the control group.
Dai et al., 2020 [114]	Pregnant mice	Sucralose solution of 0.1 mg/mL for 6 weeks	Relative abundance of Firmicutes and Proteobacteria elevated and Bacteroidetes reduced in maternal sucralose and control groups After 9 weeks of HFD the abundance of Proteobacteria decreased more significantly in the maternal sucralose group than in the control group	Higher expression of proinflammatory cytokines in maternal sucralose vs the maternal control group (p < 0.05). Exacerbation of high-fat diet-induced hepatic steatosis in 12-week-old offspring, and increases in hepatic IL-6 and tumor necrosis factor-α (TNF-α) (p < 0.05), and lipid metabolism genes (p < 0.01).
Zhengi et al., 2022 [115]	Mice	0.0003–0.3 mg/mL of sucralose	↑ Tenacibaculum, Ruegeria, Staphylococcus in jejunum, ileum and colon area. ↑ Allobaculum, ↓ Lachnoclostridium and Lachnospiraceae in the cecum of the 0.3 mg/mL group mice	No difference in body weight and liver weight between the control and treated mice. Damage to intestinal barrier and goblet cells in the treated vs. control group (p < 0.01), and distinct lymphocyte aggregation in ileum and colon.
Thomson et al., 2019 [116]	Humans	780 mg/day for 7 days	No effects	No difference in body weight. Glycemic control and insulin resistance were not affected.
Gerasimidis et al., 2019 [104]	In Vitro on human feces	5 mg/kg for 24 h	↑ Bifidobacterium and Blautia coccoides growth ↓ the Bacteroides/Prevotella ratio ↑ SCFA	Not determined
Ahmad et al., 2020 [101]	Humans	0.136 g/day for 2 weeks	No effects	SCFAs were not affected by aspartame and sucralose.
Méndez-García et al., 2022 [119]	Humans	48 mg/day for 10 weeks	↑ Blautia coccoides	Volunteers drinking sucralose for 10 weeks, but not the controls, had a larger area under the curve of glucose (AUCG) than at the beginning of the study (p = 0.02). Volunteers drinking water or sucralose for 10 weeks had similar AUCs of insulin (AUCIs) to those at the beginning of the study.
Suez et al., 2022 [103]	Humans	102 mg/day sucralose + 5900 mg/day glucose for 2 weeks Controls: 5000 mg/day glucose or no supplement	Gut microbiota alterations Changes in six Streptococcus species in the oral microbiota	Sucralose raised the glycemic response compared with glucose (p = 0.004) and no supplement control groups (p = 0.001).