Table 4.
Evidence from animal model studies relative to sucralose and saccharin effects on the gut microbiota.
| Reference | Sweeteners/Doses/Duration | Animal Model | Results |
|---|---|---|---|
| Anderson & Kirkland, 1980 [33] | Treatment: 7.5% sodium saccharin in the Purina laboratory chow Control: Cellulose 7.5% in the Purina laboratory chow Duration: 10 d |
Weaning male Charles River rats (Weight 55 ± 3 g) (n = 7) |
↑ The numbers of aerobic microbes ↓ Anaerobic/aerobic ratio |
| Serrano et al., 2021 [46] | Treatment: saccharin average daily dose equal to 4 times (250 mg/kg) the human ADI (JECFA) Control: water Duration: 10 wk |
8-wk-old mice | ↔Alpha and beta diversity and relative microbial abundances |
| Falcon et al., 2020 [47] | Control: Sucrose-sweetened yogurt (suc): low-fat yogurt supplemented with 20% sucrose, final solution concentration 11.4% sucrose Treatment: NNS-supplemented yogurt: (0.3% sodium saccharin and sodium cyclamate). Final solution concentration 0.17% NNS Duration: 17 wk |
Adult male Wistar rats (weight: 210 ± 6 g) SUC (n = 9 per group) NNS (n = 10 per group) |
↔Species richness ↔ Shannon or Simpson diversity indices |
| Abou-Donia et al., 2008 [32] | Treatment: Splenda (Sucralose) oral gavage: 1.1; 3.3; 5.5 and 11 mg/kg/d sucralose concentrations. Control: water Duration: 12 wk |
Male Sprague-Dawley rats (weight: 200–240 g) (n = 10 per group) | ↓ Number of total anaerobes and other anaerobic bacteria (Bifidobacteria, Lactobacilli, Bacteroides, and Clostridium). |
| Uebanso et al., 2017 [48] | Treatment: LS (sucralose solution of 1.5 mg/kg bw/d). HS (sucralose solution of 15 mg/kg bw/d), which is equal to the maximum ADI. Control: distilled water Duration: 8 wk |
Male and female C57Bl/6 J mice (4 wk old) (n = 8) |
LS vs. HS ↔The relative amounts of fecal total bacteria LS vs. HS ↔ Firmicutes and Bacteroidetes phylum bacteria ↓ relative Clostridium cluster XIVa, dose-dependent |
| Sánchez-Tapia et al., 2020 [49] | Treatment: Sucralose: drinking water 1.5% sucralose Control: water Duration: 4 mo |
Male Wistar rats (5 wk old) (n = 6 per group) |
↓α-diversity ↑ B. fragilis abundance |
| Wang et al., 2018 [39] | Treatment: Sucralose: drinking water sucralose (2.5%, w/v) Duration: 8 wk |
C57BL/6 mice (5 wk old) | ↔ α-diversity, Actinobacteria, and Proteobacteria ↑ Abundance of Firmicutes |
| Zhang et al., 2021 [50] | Treatment: daily gavage of Sucralose ∼ 0.43 mg, sucralose ~0.62 mg. Control: daily gavage of 2 mL normal saline Duration: 4 wk |
Obese Sprague Dawley rats (4 wk old) (8 weeks after high fat diet (HFD)) (n = 6 per group) |
0.43 mg sucralose: ↑ relative abundance of Firmicutes and ↓ Bacteroidetes 0.62 mg sucralose: ↓ relative abundance of Firmicutes ↑ Bacteroidetes The ratio of Firmicutes to Bacteroidetes in 0.43 mg sucralose was higher than that in 0.62 mg |
| Li et al., 2021 [51] | Treatment: Saccharin sodium in drinking water: 1.5 mM Control: water Duration: 4 wk |
Female Harley-white guinea pigs (Cavia porcellus) (4 wk old) (weight: 240.7 ± 7.7 g) (n= 6 per group) |
↑ Firmicutes and Lactobacillasceae-Lactobacillus abundance ↓ Relative abundance of Erysipelotrichaceae, Eubacteriaceae, and Ileibacterium |
| Bian et al., 2017 [52] | Treatment: Sucralose tap water (0.1 mg/mL). ADI (FDA) Control: tap water Duration: 6 mo |
C57BL/6 male mice (~8 wk old) (n = 10 per group) |
↑Numerous bacterial toxin genes (toxic shock syndrome toxin-1 and shiga toxin subunits) 14 genera exhibited different patterns over time in sucralose, different after 3 and/or 6 mo of treatment |
| Bian et al., 2017 [53] | Treatment: Saccharin, drinking water (0.3 mg/mL). ≈ ADI (FDA) Control: tap water Duration: 6 mo |
C57BL/6 J male mice (Weight, ~23 g, ~8 wk old) (n = 10 per group) |
Alterations of the gut metabolome with 1743 significant changes in molecular features 3 mo: ↑Sporosarcina, Jeotgalicoccus, Akkermansia, Oscillospira, and Corynebacterium ↓Anaerostipes and Ruminococcus 6 mo: ↑Corynebacterium, Roseburia, and Turicibacter ↓Ruminococcus, Adlercreutzia, and Dorea |
| Suez et al., 2014 [34] | Treatment: Commercial NAS in drinking water 10% solution: (5% saccharin, 95% glucose), (5% Sucralose), (4% Aspartame). Pure saccharin (0.1 mg ml−1) in drinking Control: water or water with 10% glucose or 10% sucrose Duration: 11 wk NAS and 5 wk pure saccharin |
Lean C57Bl/6 mice (10 wk old) with NAS treatment (n = 5 per group) C57Bl/6 mice fed on HFD with saccharin treatment (10 wk old) (n = 8 per group) |
Saccharin: dysbiosis reflected by more than 40 operational taxonomic units (OTUs) abundances changed ↑ Bacteroides genus and Clostridiales order Dysbiosis in mice that consumed pure saccharin and HFD |
| Dai et al., 2020 [54] | MS treatment: gestation and lactation, sucralose 0.1 mg/mL (FDA ADI) Offspring treatment: weaned pups fed a control diet until 8 wk of age and treated with HDF for 4 wk Control: distilled water in MS maternal control and offspring fed with a control diet Duration: maternal treatment, 6 wk |
C57BL/6 pregnant mice 3 wk old, weaned pups |
MS: at phylum level ↑ the relative abundance of Verrucomicrobia and Proteobacteria and ↓Bacteroidetes At genus level ↑ abundance of Akkermansia, Blautia, Corynebacterium, Robinsoniella, and ↓ Alistipes, Barnesiella, Paraprevotella, Saccharibacteria genera incertae sedis, and Streptococcus MS alters the gut microbiota in the offspring, ↓alpha diversity of 3-wk-old pups |
ADI: Acceptable daily intake; MS: maternal sucralose; d: day; wk: weeks, mo: months; HFD: high-fat diet; LS: low saccharin; HS: high saccharin. ↔: unmodified; ↑: increase; ↓: decrease.