There are serious indications that artificial sweeteners such as saccharin, sucralose and aspartame can disrupt the gut microbiome and negatively affect blood sugar regulation, partly through demonstrable mechanisms in the gut. The research is not yet conclusive, however: large randomised trials in humans are lacking, and small human studies sometimes find no effect. Chronic use at high doses warrants caution, but a definitive ban based on current evidence is not scientifically justified.
Artificial sweeteners (also called non-nutritive sweeteners or NNS, such as saccharin, sucralose, aspartame and acesulfame-K) have been under scientific scrutiny for years because of their possible influence on the gut microbiome. The results are mixed: some studies show that they disrupt the composition of the gut microbiome, but several randomised controlled trials find no significant effect. No scientific consensus has been reached yet.
The most striking evidence comes from research in which mice and healthy humans were given saccharin, sucralose, aspartame or acesulfame-K. In those studies, glucose tolerance decreased -- that is, the body's ability to regulate blood sugar properly. That effect could even be transferred via faecal transplantation to other animals, which suggests that the gut microbiome plays a direct causal role. This is therefore not merely a side effect, but possibly a mechanism by which sweeteners influence blood sugar regulation through the gut microbiome.
A small randomised trial with only 17 healthy adults found no measurable changes in the gut microbiome or in the production of short-chain fatty acids (substances that gut bacteria produce from fibre and that are beneficial for insulin sensitivity and gut health), even at realistic daily doses of aspartame or sucralose over two weeks. That study is too small to draw definitive conclusions from, but it shows that an effect is far from always visible.
The broader picture sketched by multiple studies is more worrying than that one small study suggests. Chronic use of artificial sweeteners is linked in several studies to insulin resistance, non-alcoholic fatty liver disease and gastrointestinal complaints. A large cohort study also found an association with a higher risk of cardiovascular disease, stroke, cancer and total mortality. Importantly, these are observational associations, not proven causal relationships. People who use a lot of sweeteners may also have an unhealthier lifestyle for other reasons.
A disrupted gut microbiome, such as occurs in obesity, makes the gut wall more permeable and causes low-grade inflammation that further disrupts glucose metabolism. This mechanism has been demonstrated both in mice and in human gut tissue. If artificial sweeteners do indeed alter the gut microbiome, they could contribute through this pathway to a downward spiral. But whether that actually plays out in practice at ordinary levels of consumption has not yet been conclusively proven.
The practical conclusion is therefore: saccharin stands out most negatively in mechanistic research, and the strongest indications of an effect on blood sugar regulation via the gut microbiome have been seen in mice and in limited human research with saccharin, sucralose, aspartame and acesulfame-K combined. No study in the available sources designates any one specific sweetener as completely safe, but there is also no evidence that all sweeteners cause harm in everyone. Those with concerns about blood sugar regulation or gut health would be wise to limit their use of artificial sweeteners, especially when that use is chronic and at high doses.
Sources include several review and cohort studies (PMID 37111090, 36364710, 29159583, 39339762), a mouse study with faecal transplantation (PMID 25231862), a mechanistic study in mice and human tissue (PMID 36948576), a meta-analysis on short-chain fatty acids (PMID 35163038) and a small RCT in humans (PMID 33171964, n=17). No large independent RCTs with hard clinical endpoints are available.