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

A recent study published within the journal Nutrition reviewed the available evidence on the consequences of low- and non-calorie sweeteners (LNCSs) on the gut microbiota.

Higher rates of obesity, metabolic syndrome, type 2 diabetes, and cardiovascular diseases have develop into a major public health concern. Increased sugar intake has been identified because the explanation for these disorders, resulting in the introduction of non-nutritive sweeteners (NNSs). Alternative sweeteners contain no or few calories, and their use has substantially increased over time. It has been reported that 40% of adults in the US (US) consumed alternative sweeteners between 2009 and 2012, 54% higher than the estimates from 1999 and 2000.

Study: Effect of low-and non-calorie sweeteners on the gut microbiota: A review of clinical trials and cross-sectional studies

Whether sweeteners lack any harmful effects continues to be debated. Some studies report links between the intake of different sweeteners and shifts in physiological parameters, akin to insulin resistance (IR) and glucose tolerance, with the gut microbiota implicated in mediating these effects. Further, studies have demonstrated associations between low gut microbial richness and increases in IR, dyslipidemia, adiposity, and inflammation. Dietary patterns can modulate the gut microbiota, thus influencing the physiological aspects linked to metabolic diseases.

The study and findings

In the current study, researchers analyzed the present evidence on the consequences of LNCSs on the gut microbiota. PubMed and Ovid databases were looked for cross-sectional studies and clinical trials. Only studies including healthy populations were chosen. Studies that evaluated the oral microbiota were excluded. The preliminary search yielded 465 records; after duplicate screening and exclusions, full texts of 14 articles were reviewed. Overall, 11 studies – 4 cross-sectional studies and eight clinical trials – were included for evaluation.

One study comprised each cross-sectional and clinical trial protocols. Six trials were randomized controlled trials; one was a non-randomized uncontrolled trial, and one was a randomized uncontrolled trial. The studies were conducted between 2006 and 2022 within the US, the UK (UK), Europe, Israel, Canada, and Chile. Two trials assessed the consequences of saccharin on the gut microbiota; one investigated sucralose, three examined polyols, and two studied multiple NNSs.

Two cross-sectional studies evaluated the associations between the consumption of artificially sweetened beverages (ASB) and the microbiota composition; one study focused on the consumption of aspartame and acesulfame-K, while the opposite evaluated global artificial sweetener consumption. One trial found no effect of supplementing 800 mg of saccharin to 46 individuals for 2 weeks. In contrast, the opposite trial noted that the microbiota clustered in another way in individuals with poorer glycemic response than those with normal glycemic response.

One other trial found no changes within the gut microbiota after sucralose supplementation. Meanwhile, a two-week sucralose supplementation altered the gut microbiota in a distinct study, increasing Dorea longicatena and Eubacterium. Likewise, the aspartame trial observed no gut microbiota alterations after a two-week intervention. Studies investigating polyols (isomalt, lactitol, and maltitol) revealed their useful impact on the gut microbiota.

Specifically, the consumption of those 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. Besides, a positive correlation was reported between artificial sweeteners and various taxonomic entities, akin to Actinomycetota, Enterobacteriaceae, and Deltaproteobacteria.

A Swedish study examined the consumption of ASB or naturally sweetened beverages amongst 1,085 healthy adults and located no associations between ASB consumption and microbiota changes. Further, a Canadian study analyzing ASB consumption amongst infants and their moms found that maternal ASB intake was related to the depletion of Bacteroides spp in infants. In a single study, sucralose and saccharin supplementation impaired participants’ glycemic response.

Germ-free mice receiving the microbiome from participants with impaired glucose tolerance (responders) developed an increased glycemic response than those receiving the microbiome from non-responders. Just a few trials suggested that the glycemic response to NNSs was partly driven by baseline interindividual differences within the gut microbiota. Specifically, individuals with higher post-intervention insulinemia had distinct baseline microbiota composition independent of placebo or sucralose consumption.


In summary, two clinical trials suggested that NNSs altered the gut microbiota and revealed a causal effect between sucralose or saccharin intake and impaired glucose tolerance in mice. Trials on polyols suggested the useful effects on the microbiota. Just a few cross-sectional studies noted associations between the consumption of different sweeteners and detrimental gut microbiota changes.

Furthermore, the baseline microbiota composition could modulate glycemic and microbial response to LNCSs. The heterogeneity in findings across studies may very well be attributed to the small sample sizes, methodological differences, short/various intervention periods, and individualized responses to LNCSs. Overall, studies in larger cohorts with more realistic sweetener doses and longer durations are required to corroborate these findings.

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