β-carotene-producing bacteria residing in the intestine provide vitamin A to mouse tissues in vivo

J Nutr. 2014 May;144(5):608-13. doi: 10.3945/jn.113.188391. Epub 2014 Mar 5.

Abstract

Vitamin A deficiency (VAD) is an overwhelming public health problem that affects hundreds of millions of people worldwide. A definitive solution to VAD has yet to be identified. Because it is an essential nutrient, vitamin A or its carotenoid precursor β-carotene can only be obtained from food or supplements. In this study, we wanted to establish whether β-carotene produced in the mouse intestine by bacteria synthesizing the provitamin A carotenoid could be delivered to various tissues within the body. To achieve this, we took advantage of the Escherichia coli MG1655*, an intestine-adapted spontaneous mutant of E. coli MG1655, and the plasmid pAC-BETA, containing the genes coding for the 4 key enzymes of the β-carotene biosynthetic pathway (geranylgeranyl pyrophosphate synthase, phytoene synthase, phytoene desaturase, and lycopene cyclase) from Erwinia herbicola. We engineered the E. coli MG1655* to produce β-carotene during transformation with pAC-BETA (MG1655*-βC) and gavaged wild-type and knockout mice for the enzyme β-carotene 15,15'-oxygenase with this recombinant strain. Various regimens of bacteria administration were tested (single vs. multiple and low vs. high doses). β-Carotene concentration was measured by HPLC in mouse serum, liver, intestine, and feces. Enumeration of MG1655*-βC cells in the feces was performed to assess efficiency of intestinal colonization. We demonstrated in vivo that probiotic bacteria could be used to deliver vitamin A to the tissues of a mammalian host. These results have the potential to pave the road for future investigations aimed at identifying alternative, novel approaches to treat VAD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotenoids / metabolism
  • Erwinia / enzymology*
  • Erwinia / genetics
  • Escherichia coli / enzymology*
  • Escherichia coli / genetics
  • Feces / microbiology
  • Female
  • Geranylgeranyl-Diphosphate Geranylgeranyltransferase / genetics
  • Geranylgeranyl-Diphosphate Geranylgeranyltransferase / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / microbiology*
  • Intramolecular Lyases / genetics
  • Intramolecular Lyases / metabolism
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Probiotics
  • Vitamin A / biosynthesis*
  • Vitamin A Deficiency / metabolism
  • Vitamin A Deficiency / microbiology
  • Vitamin A Deficiency / therapy*
  • beta Carotene / metabolism*
  • beta-Carotene 15,15'-Monooxygenase / genetics
  • beta-Carotene 15,15'-Monooxygenase / metabolism

Substances

  • beta Carotene
  • Vitamin A
  • Carotenoids
  • Oxidoreductases
  • phytoene dehydrogenase
  • beta-Carotene 15,15'-Monooxygenase
  • Geranylgeranyl-Diphosphate Geranylgeranyltransferase
  • Intramolecular Lyases
  • lycopene cyclase-isomerase