Non-Caloric Artificial Sweeteners Modulate the Expression of Key Metabolic Genes in the Omnipresent Gut Microbe <b><i>Escherichia coli</i></b>

Abstract

The human gut is inhabited by several hundred different bacterial species. These bacteria are closely associated with our health and well-being. The composition of these diverse commensals is influenced by our dietary intakes. Non-caloric artificial sweeteners (NAS) have gained global popularity, particularly among diabetic patients, due to their perceived health benefits, such as reduction of body weight and maintenance of blood glucose level compared to caloric sugars. Recent studies have reported that these artificial sweeteners can alter the composition of gut microbiota and, thus, affect our normal physiological state. Here, we investigated the effect of aspartame and acesulfame potassium (ace-K), two popular NAS, in a commercial formulation on the growth and metabolic pathways of omnipresent gut commensal Escherichia coli by analyzing the relative expression levels of the key genes, which control over twenty important metabolic pathways. Treatment with NAS preparation (aspartame and ace-K) modulates the growth of E. coli as well as inducing the expression of important metabolic genes associated with glucose (pfkA, sucA, aceE, pfkB, lpdA), nucleotide (tmk, adk, tdk, thyA), and fatty acid (fabI) metabolisms, among others. Several of the affected genes were previously reported to be important for the colonization of the microbes in the gut. These findings may shed light on the mechanism of alteration of gut microbes and their metabolism by NAS.

Aspartame, acesulfame K and sucralose- influence on the metabolism of Escherichia coli

“…Nine key regulatory enzymes (aceE, adk, fabI, glgC, lpd, pfkA, pfkB, tdk1 and thyA) that control important metabolic pathways [ 37 ] in E. coli were selected from the Rate-Limiting Enzyme database (RLEdb) [ 38 ] for corresponding gene expression analysis. The gene encoding DNA gyrase (gyrA) was used as the reference to normalize gene expression data.…”

“…Relevant information about the primers is given in Refs. [ 37 ]. Gene expression levels in the presence of different NAS were compared using relative quantitative PCR with PowerUp™ SYBR™ Green Master Mix (A25780, Thermo Fisher Scientific) in StepOnePlus™ Real-Time PCR machine (Applied Biosystems).…”

“…In the present study, we investigated and compared the influence of acesulfame potassium, aspartame and sucralose on the growth and metabolism of E. coli . In a previous study, we found that a commercially available artificial sweetener preparation containing a combination of aspartame and acesulfame potassium can influence E. coli growth and modulate the expression of some of its key regulatory genes associated with glucose, nucleotide and fatty acid metabolism [ 37 ]. In the present study, we investigated and compared the influence of acesulfame potassium, aspartame and sucralose per se on the growth and metabolism of E. coli .…”

Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies

“…Regarding the bacteriostatic effect of Ace-K, this sweetener shows a strong inhibitory effect on the growth of E. coli HB101 and E. coli K-12 [28]. In contrast, using a concentration of Ace-K of 2.5 mg/mL, the result was an induction in E. coli growth, whereas the growth stimulation decreased gradually when higher concentrations of sweetener were used [18].…”

“…The study by Mahmud et al analyzes the combined and individual effects of the administration of low concentrations of aspartame and Ace-K. Induction of Escherichia coli growth and expression of some important genes which may be related to its colonization in the gut were observed [18]. In another study with human fecal samples, aspartame administration significantly increased Bifidobacterium and Blautia coccoides growth and decreased the Bacteroides/Prevotella ratio; nevertheless, the aspartame-based sweetener used in this study was rich in maltodextrin, thus, the authors did not study the effect of aspartame alone [19].…”