**7.** *E. coli* **as synbiotic**

The beneficial effects of probiotic *E. coli* strains are contributed by their functions in the small intestine as well as in the colon. However, prebiotics are nutrients for the survival and maintenance of the colonic microbiome, which secrete host-beneficial SCFA as fermentation products [66]. Synbiotics are a mixture of prebiotics and probiotics, which provide synergistic effects of both components [67]. Dietary fructose and sucrose are implicated in the onset and progression of metabolic diseases [68, 69]. EcN::*vgb-gfp* was modified with two different synthetic operons containing *Ptac-pqq-glf-mtlK* and *Ptac-pqq-fdh* that convert dietary fructose into mannitol and 5-keto-D-fructose that are prebiotics in the small intestine [45]. These prebiotics then serve as nutrients for colonic bacteria to produce SCFA. PQQ secreted by the synbiotic EcN will scavenge reactive oxygen species produced by fructose. Both mannitol and 5-keto-D-fructose producing strains demonstrated synbiotic activities by preventing dietary fructose-mediated metabolic disorders in rats. Fructose is known to improve iron status by its reductive ability compared to other sugars [70]. However, metabolic complications of fructose hindered its applicability. Since EcN synbiotics overcome the negative effects of fructose, these strains were found to also improve iron status [71].

High dietary sucrose also contributes to the metabolic disorders [68]. Inulosucrase catalyzes the conversion of sucrose into inulin [72]. Probiotic Ec16 transformed with inulosucrase of *Lactobacillus johnsonii* NCC 533 resulted in its secretion in the supernatant, while the enzyme was localized in the periplasm of *E. coli* BL21 suggested that extracellular enzyme in Ec16 could get transported using colicin E1/1a1b transport system [22]. EcN genomic integrant with *vgb-gfppqqABCDE-inuJ* gene cluster prevented high sucrose-induced metabolic disorders in rats by increased PQQ and SCFA [46].
