Background Gut microbes play a crucial role in the maintenance of human health. Components in the diet of the host affect their metabolism and diversity. Here, we investigated the influences of three commonly used non-caloric artificial sweeteners-aspartame, acesulfame K and sucralose-on the growth and metabolism of an omnipresent gut microbe Escherichia c oli K-12. Methods : Growth of E. coli in the presence of aspartame, acesulfame K and sucralose in media was assessed and the influences of these artificial sweeteners on metabolism were investigated by relative expression analysis of genes encoding the rate limiting steps of important metabolic pathways as well as their global metabolomic profiles. Results: As a whole, E. coli growth was inhibited by aspartame and induced by acesulfame potassium, while the effect of sucralose on growth was less prominent. Although the expressions of multiple key enzymes that regulate important metabolic pathways were significantly altered by all three sweeteners, acesulfame K caused the most notable changes in this regard. In multivariate analysis with the metabolite profiles, the sucralose-treated cells clustered the closest to the untreated cells, while the acesulfame potassium treated cells were the most distant. These sweeteners affect multiple metabolic pathways in E. coli , which include propanoate, phosphonate, phosphinate and fatty acid metabolism, pentose phosphate pathway, and biosynthesis of several amino acids including lysine and the aromatic amino acids. Similar to the gene expression pattern, acesulfame potassium treated E. coli showed the largest deviation in their metabolite profiles compared to the untreated cells.
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.
Methylenetetrahydrofolate reductase (MTHFR) has been reported as a key enzyme not only for intracellular folate homeostasis but also for metabolism. A particular variant (G677A) leads to an altered amino acid, which ultimately causes decreased enzyme activity and may modulate the risk of causing several chronic diseases. The purpose of this study was to detect the pervasiveness of this variant MTHFR rs1801133 G677A in the Bangladeshi population. We applied allele-specific polymerase chain reaction (AS-PCR) to determine the genotypes at the rs1801133 in the Bangladeshi population. We performed targeted sequencing of the AS-PCR product of randomly selected samples. Out of the 181 Bangladeshi individuals, 71.8% had homozygous 677GG genotype, while 28.2% comprised of heterozygous 677GA genotype. No individual with the homozygous 677AA genotype was found in this representative Bangladeshi population. The 677G alleles had higher frequency (0.856) compared to 677A alleles (0.144) at the rs1801133 locus. Though the more risky homozygous 677AA genotype at the rs1801133 locus is absent in the Bangladeshi population, further association studies can be performed to identify the role of MTHFR mutation in the susceptibility to different multifactorial diseases.
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