An engineered Escherichia coli Nissle 1917 increase the production of indole lactic acid in the gut

Abstract

The expanding knowledge of the health impacts of the metabolic activities of the gut microbiota reinforces the current interest in engineered probiotics. Tryptophan metabolites, in particular indole lactic acid (ILA), are attractive candidates as potential therapeutic agents. ILA is a promising compound with multiple beneficial effects including amelioration colitis in rodent models of necrotizing enterocolitis, as well as improved infant immune system maturation. In this work we engineered and characterized in vitro and in vivo an Escherichia coli Nissle 1917 strain that produces ILA. The 2-step metabolic pathway comprises aminotransferases native of E. coli and a dehydrogenase introduced from Bifidobacterium longum subspecies infantis. Our results show a robust engineered probiotic that produces 73.4 ± 47.2 nmol and 149 ± 123.6 nmol of ILA per gram of fecal and cecal matter, respectively, three days after colonization in a mouse model. In addition, hereby is reported an engineered-probiotic-related increase of ILA in the systemic circulation of the treated mice. This strain serves as proof of concept for the transfer of capacity to produce ILA in vivo and as ILA emerges as a potent microbial metabolite against gastrointestinal inflammation, further development of this strain offers efficient options for ILA-focused therapeutic interventions in situ.

Fucoxanthin restructures the gut microbiota and metabolic functions of non-obese individuals in an in vitro fermentation model

“…27 The significantly increased indoleacetic acid in the current study indicates potential benefits including amelioration colitis in rodent models of necrotizing enterocolitis, as well as improved infant immune system maturation. 28 Also, pindolol showed an antidepressant effect in mice 29 and molindone possesses psychopharmacological benefits in children. 30 However, the relative abundance of indoleacrylic acid and l -tryptophan was significantly reduced by fucoxanthin compared with the control, which indicates that fucoxanthin-stimulated tryptophan catabolism and indoleacrylic acid-conversion microbiota were suppressed.…”