Abstract
AimsTo assess protective efficacy of genetically modified Escherichia coli Nissle 1917 (EcN) on metabolic effects induced by chronic consumption of dietary fructose.Materials and MethodsEcN was genetically modified with fructose dehydrogenase (fdh) gene for conversion of fructose to 5-keto-D-fructose and mannitol-2-dehydrogenase (mtlK) gene for conversion to mannitol, a prebiotic. Charles foster rats weighing 150–200 g were fed with 20% fructose in drinking water for two months. Probiotic treatment of EcN (pqq), EcN (pqq-glf-mtlK), EcN (pqq-fdh) was given once per week 109 cells for two months. Furthermore, blood and liver parameters for oxidative stress, dyslipidemia and hyperglycemia were estimated. Fecal samples were collected to determine the production of short chain fatty acids and pyrroloquinoline quinone (PQQ) production.ResultsEcN (pqq-glf-mtlK), EcN (pqq-fdh) transformants were confirmed by restriction digestion and functionality was checked by PQQ estimation and HPLC analysis. There was significant increase in body weight, serum glucose, liver injury markers, lipid profile in serum and liver, and decrease in antioxidant enzyme activity in high-fructose-fed rats. However the rats treated with EcN (pqq-glf-mtlK) and EcN (pqq-fdh) showed significant reduction in lipid peroxidation along with increase in serum and hepatic antioxidant enzyme activities. Restoration of liver injury marker enzymes was also seen. Increase in short chain fatty acids (SCFA) demonstrated the prebiotic effects of mannitol and gluconic acid.ConclusionsOur study demonstrated the effectiveness of probiotic EcN producing PQQ and fructose metabolizing enzymes against the fructose induced hepatic steatosis suggesting that its potential for use in treating fructose induced metabolic syndrome.
Highlights
Fructose, present in high fructose corn syrup, is known to induce metabolic syndrome leading to type 2 diabetes mellitus, cardiovascular disease and mortality [1, 2]
Our study demonstrated the effectiveness of probiotic Escherichia coli Nissle 1917 (EcN) producing pyrroloquinoline quinone (PQQ) and fructose metabolizing enzymes against the fructose induced hepatic steatosis suggesting that its potential for use in treating fructose induced metabolic syndrome
The pAN1 plasmid possessing G. suboxydans pqq operon, the pAN2 plasmid containing G. frauteuri IFO3260 fdh gene cluster, the pAN3 plasmid harbouring Z. mobilis glf gene, the pAN4 plasmid containing L. brevis mtlK gene, the pAN5 plasmid possessing pqq operon and glf gene together, the pAN6 plasmid containing pqq operon, glf gene and mtlK together, the pAN7 plasmid harbouring pqq operon and fdh together under constitutive tac promoter were cloned in pJET vector (S1 Fig)
Summary
Present in high fructose corn syrup, is known to induce metabolic syndrome leading to type 2 diabetes mellitus, cardiovascular disease and mortality [1, 2]. Fructose is converted to triglycerides (TG) through de novo lipogenesis when taken in excess amount building up lipids in the liver [3] These lead to elevated blood lipid levels resulting into inflammation, insulin resistance, increased oxidative stress, and blood glucose levels. In rats fed with high fructose diet, probiotic treatment has been shown to significantly reduce oxidative stress, insulin resistance and lipogenesis [5]. Prebiotic such as short chain fatty acids (SCFA) stimulates fatty acid oxidation, inhibits lipogenesis, and glucose production through inhibition of gluconeogenic gene expression [6, 7]. The combination of prebiotic and probiotic known as “synbiotic” synergistically promotes the growth and survival of existing beneficial bacteria along with the newly added probiotic strains in the colon [10]
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