A recent study published in Eating reviewed the available evidence on the effects of low-calorie and non-caloric sweeteners (LNCS) on the gut microbiota.
Higher rates of obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease have become significant public health concerns. Increased sugar intake has been identified as a cause of these disorders, leading to the introduction of non-nutritive sweeteners (NNS). Alternative sweeteners contain no or few calories and their use has increased significantly over time. 40% of adults in the United States (US) were reported to have consumed alternative sweeteners between 2009 and 2012, a 54% increase over estimates from 1999 and 2000.
Study: Effect of low-calorie and no-calorie sweeteners on gut microbiota: Review of clinical trials and cross-sectional studies
Whether sweeteners have any harmful effects is still debated. Some studies have reported associations between the intake of alternative sweeteners and changes in physiological parameters such as insulin resistance (IR) and glucose tolerance, with gut microbiota being implicated in mediating these effects. Additionally, studies have shown associations between low gut microbial richness and increases in IR, dyslipidemia, obesity, and inflammation. Dietary patterns can modulate the gut microbiota, thereby influencing physiological factors associated with metabolic diseases.
The study and findings
In the present study, researchers analyzed the current evidence for the effects of LNCS on gut microbiota. PubMed and Ovid databases were searched for cross-sectional studies and clinical trials. Only studies involving healthy populations were selected. Studies that assessed the oral microbiota were excluded. The preliminary search yielded 465 records; after duplicate screening and exclusion, the full texts of 14 articles were reviewed. A total of 11 studies – four cross-over studies and eight clinical trials – were included for analysis.
One study included cross-sectional and clinical trial protocols. Six studies 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 in the United States, United Kingdom (UK), Europe, Israel, Canada and Chile. Two studies evaluated the effects of saccharin on gut microbiota; one studied sucralose, three studied polyols, and two studied multiple NNS.
Two cross-sectional studies assessed associations between artificially sweetened beverage (ASB) consumption and microbiota composition; one study focused on the consumption of aspartame and acesulfame-K, while the other assessed global consumption of artificial sweeteners. One study found no effect of supplementing 46 individuals with 800 mg of saccharin for two weeks. In contrast, the other study noted that the microbiota clustered differently in individuals with a poor glycemic response than those with a normal glycemic response.
Another study found no changes in gut microbiota after sucralose supplementation. Meanwhile, two weeks of sucralose supplementation changed the gut microbiota in another study, increasing He wanted the long one and Eubacterium. Similarly, the aspartame trial did not observe changes in gut microbiota after a two-week intervention. Studies investigating polyols (isomalt, lactitol and maltitol) reveal their beneficial effects on the gut microbiota.
Specifically, consumption of these polyols significantly increases the population of bifidobacteria. A cross-sectional study identified a difference in microbial diversity between users of acesulfame-K or aspartame and nonusers. In addition, a positive correlation has been reported between artificial sweeteners and multiple taxonomic units, 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 microbiota changes. Additionally, a Canadian study analyzing ASB consumption among infants and their mothers found that maternal ASB intake was associated with depletion of Bacteroides spp in infants. In one study, sucralose and saccharin supplements worsened participants’ glycemic response.
Germ-free mice receiving the microbiome from participants with impaired glucose tolerance (responders) developed an increased glycemic response compared to those receiving the microbiome from non-responders. Several studies have suggested that the glycemic response to NNSs is partially driven by baseline interindividual differences in gut microbiota. Specifically, individuals with higher post-intervention insulinemia had a different baseline microbiota composition regardless of placebo or sucralose intake.
Conclusions
In summary, two clinical trials suggest that NNSs alter the gut microbiota and reveal a causal effect between sucralose or saccharin intake and impaired glucose tolerance in mice. Experiments with polyols show the beneficial effect on the microbiota. Several cross-sectional studies have noted associations between consumption of alternative sweeteners and deleterious changes in gut microbiota.
Furthermore, the composition of the baseline microbiota may modulate the glycemic and microbial response to LNCS. Heterogeneity in findings across studies may be due to small sample sizes, methodological differences, short/variable intervention periods, and individualized responses to the LNCS. Overall, larger cohort studies with more realistic sweetener doses and longer durations are needed to confirm these findings.
