Saccharin
Old Controversy, Renewed Evidence
Once Banned, Now Back in Circulation
Saccharin, first synthesized in 1879 and previously labeled a potential carcinogen, was exonerated in 2000 after rat-based bladder cancer findings failed to translate to humans . Since FDA removed warning labels, it’s been quietly used in diet drinks and tabletop packets again—without public scrutiny.
Modern Microbiome Disruption
A 2025 study tracking 6‑month saccharin intake in mice (at human ADI doses) uncovered liver inflammation and gut microbiome dysbiosis, marked by increased iNOS and TNF-α and shifts in bacterial genera (e.g., ↓ Anaerostipes, ↑ Akkermansia, Corynebacterium).
Frontiers microbiome analysis notes saccharin severely suppresses gut diversity—more so and more persistently than other sweeteners.
Human-controlled experiments mirror these findings: even 6 days of saccharin (5 mg/kg/day) altered gut flora and reduced glucose tolerance in 4 out of 7 healthy participants.
Antimicrobial Activity: Helpful or Harmful?
Saccharin’s metabolism-independent journey through the gut allows it to act directly on bacteria—new research shows it can destabilize cell envelopes, disrupt DNA replication, and even revive antibiotic efficacy.
But there's a dark side: antimicrobial activity can disturb gut homeostasis, potentially creating opportunities for opportunistic pathogens.
Mixed Effects on Gut Inflammation
One MDPI mouse study showed saccharin reduced colitis symptoms—suggesting context-dependent effects where dampening microbial load could help conditions like SIBO or pouchitis.
However, these anti-inflammatory benefits contrast with the pro-inflammatory liver results seen elsewhere—hinting at complex, dose- and condition-specific impacts .
What About Cancer?
Human cohort data show no link between saccharin and bladder cancer. Regulatory agencies maintain its Group 3 (not classifiable) status—yet disruption of microbiome and inflammation opens speculative pathways for metabolic harm.
Saccharin induced liver inflammation in mice by altering the gut microbiota and its metabolic functions
Zhao et al., 2017
C57BL/6J male mice exposed to saccharin (human-equivalent ADI levels) for six months showed elevated hepatic expression of pro-inflammatory genes (iNOS, TNF‑α). 16S rRNA sequencing and metabolomics revealed significant shifts in gut bacteria (e.g., ↓ Anaerostipes, Ruminococcus; ↑ Akkermansia) and microbial metabolic profiles. Data support gut microbiota as a mediator of saccharin-associated inflammation.