Study probes the hidden impact of low-cal sweeteners on gut health

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A recent study published in the journal Power supply reviewed the available evidence on the effects of low-calorie and non-calorie sweeteners (LNCSs) on the gut microbiota.

Higher rates of obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease have become a major public health problem. Increased sugar intake has been found to be the cause of these conditions, leading to the introduction of non-nutritive sweeteners (NNSs). Alternative sweeteners contain no or few calories and their use has increased significantly over time. It has been reported that 40% of adults in the United States (US) consumed alternative sweeteners between 2009 and 2012, 54% more than 1999 and 2000 estimates.

Research: Effect of low- and no-calorie sweeteners on the gut microbiota: a review of clinical trials and cross-sectional studies

Whether sweeteners have harmful effects is still debated. Some studies report associations between the intake of alternative sweeteners and shifts in physiological parameters, such as insulin resistance (IR) and glucose tolerance, with the gut microbiota involved in mediating these effects. Furthermore, studies have shown associations between low intestinal microbial richness and an increase in IR, dyslipidemia, adipose tissue and inflammation. Dietary patterns can modulate the gut microbiota and thus influence physiological factors associated with metabolic diseases.

The research and findings

In the current study, researchers analyzed current evidence on the effects of LNCSs on the gut microbiota. PubMed and Ovid databases were searched for cross-sectional studies and clinical trials. Only studies involving healthy populations were selected. Studies evaluating the oral microbiota were excluded. The preliminary research yielded 465 records; after double screening and exclusions, the full texts of 14 articles were assessed. A total of eleven studies – four cross-sectional studies and eight clinical studies – were included for analysis.

One study included both cross-sectional and clinical study protocols. Six studies were randomized controlled trials; one was a nonrandomized, uncontrolled trial, and one was a randomized, uncontrolled trial. The studies were conducted between 2006 and 2022 in the US, United Kingdom (UK), Europe, Israel, Canada and Chile. Two studies assessed the effects of saccharin on the gut microbiota; one examined sucralose, three examined polyols, and two studied multiple NNSs.

Two cross-sectional studies evaluated associations between artificially sweetened beverage (ASB) consumption and microbiota composition; one study focused on the consumption of aspartame and acesulfame-K, while the other evaluated global consumption of artificial sweeteners. One trial found no effect from supplementing 800 mg of saccharin to 46 people for two weeks. In contrast, the other study noted that the microbiota clustered differently in individuals with poorer glycemic response than in individuals with normal glycemic response.

Another study found no changes in the gut microbiota after sucralose supplementation. Meanwhile, in another study, two weeks of sucralose supplementation changed and increased gut microbiota He wanted the long one And Eubacterium. Similarly, the aspartame study observed no changes in the gut microbiota after a two-week intervention. Studies investigating polyols (isomalt, lactitol and maltitol) revealed their beneficial influence on the intestinal microbiota.

Specifically, consumption of these polyols significantly increased the bifidobacterial population. One cross-sectional study identified a difference in microbial diversity between consumers of acesulfame-K or aspartame and non-consumers. Furthermore, a positive correlation was reported between artificial sweeteners and numerous taxonomic entities, such as Actinomycetota, Enterobacteriaceae and Deltaproteobacteria.

A Swedish study examined consumption of ASB or naturally sweetened beverages among 1,085 healthy adults and found no association between ASB consumption and changes in microbiota. Furthermore, a Canadian study that analyzed ASB consumption among infants and their mothers found that maternal ASB intake was associated with ASB depletion. Bacteroides spp in infants. In one study, sucralose and saccharin supplementation reduced participants’ glycemic response.

Germ-free mice that received the microbiome from participants with impaired glucose tolerance (responders) developed an increased glycemic response than mice that received the microbiome from non-responders. A few studies suggested that the glycemic response to NNS was partly mediated by inter-individual differences in the gut microbiota at baseline. In particular, subjects with higher insulinemia after the intervention had different microbiota composition at baseline, independent of placebo or sucralose consumption.


In summary, two clinical studies suggested that NNS altered the gut microbiota and revealed a causal effect between sucralose or saccharin intake and impaired glucose tolerance in mice. Tests with polyols suggested beneficial effects on the microbiota. A few cross-sectional studies indicated associations between the consumption of alternative sweeteners and deleterious changes in the gut microbiota.

Furthermore, the basic composition of the microbiota could modulate the glycemic and microbial response to LNCSs. The heterogeneity in findings between studies may be attributed to small sample sizes, methodological differences, short/varying intervention periods, and individualized responses to LNCSs. Overall, studies in larger cohorts with more realistic sweetener doses and longer durations are needed to confirm these findings.

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