Table 5.

Studies on the effect of saccharin on the gut microbiota.

REFERENCE	SPECIES	DOSE OF SACCHARIN AND EXPOSURE	OUTCOMES	CLINICAL OUTCOMES
Suez et al., 2014 [70]	Mice	High fat diet + 5 mg/kg b.w./day of saccharin for 5 weeks	↑ Bacteroides, Clostridiales; ↓ Lactobacillus reuteri	Impaired glucose tolerance (p < 0.0002). Increased fecal levels of the SCFAs propionate (p < 0.1).
Bian et al., 2017 [121]	Male mice	0.3 mg/mL of saccharin in drinking water for 6 months	at 3 months: ↑ Sporosarcina, Jeotgalicoccus, Akkermansia, Oscillospira, and Corynebacterium; ↓ Anaerostipes and Ruminococcus at 6 months: ↑ Corynebacterium, Roseburia, and Turicibacter; ↓ Ruminococcus, Adlercreutzia, and Dorea	Increase in hepatic pro-inflammatory genes, inducible nitric oxide synthase, and TNF-α, (p < 0.05) after 6 months of treatment.
Nogueira et al., 2019 [122]	Dogs	0.02% of saccharin + eugenol for 10 days 0.02% of saccharin + eugenol + 5% fiber +prebiotic blend for 10 days 5% fiber + prebiotic blend diet for 10 days 5% cellulose for 10 days	No effects	No significant effects
Serrano et al., 2021 [123]	Mice (WT and T1R2-KO)	250 mg/kg bw/day	No significant effects	T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance vs WT mice.
Murali et al., 2022 [109]	Mice	20 or 100 mg/kg b.w./day for 4 weeks	No significant effect on the fecal microbiota	No mortality, no abnormalities, no signs of clinical toxicity Normal fecal consistency
Daly et al., 2014 [124]	Piglets	Basal diet for 2 weeks Basal diet + 5% (w/w) lactose for 2 weeks Basal diet + 0.015 % (w/w) saccharin for 2 weeks	↑ cecal Lactobacillus populations, particularly Lactobacillus OTU4228	No significant changes
Daly et al., 2016 [125]	Piglets	Basal diet for 2 weeks Basal diet + 0.015 % (w/w) saccharin for 2 weeks	↑ Lactobacillaceae population, particularly Lactobacillus OTU4228	No significant changes
Suez et al., 2014 [70]	Human	5 mg/kg b.w./day for 1 week	↑ Bacteroides fragilis and Weissella cibaria ↓ Candidatus Arthromitus	Four out of seven subjects developed significantly poorer glycemic responses 5–7 days after saccharin consumption, compared to their glycemic responses on days 1–4 (p < 0.001).
Serrano et al., 2021 [123]	Human	400 mg/day for 2 weeks 400 mg/day + 670 mg/day lactisole for 2 weeks 670 mg/day lactisole placebo	No significant effects	No significant effects
Suez et al., 2022 [103]	Human	180 mg/day saccharin + 5820 mg/day glucose for 2 weeks 5000 mg/day glucose for 2 weeks No supplement control	Gut microbiota alterations (not specified) ↓ relative abundance of Fusobacterium in the oral microbiota	Saccharin raised a glycemic response compared to glucose (p = 0.042) and no supplement control groups (p = 0.018).