title: β-carotene-producing bacteria residing in the intestine provide vitamin A to mouse tissues in vivo.
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.
authors.affiliation: Departments of Food Science and.
authors.forename: Lesley
authors.initials: L
authors.lastname: Wassef
authors.forename: Ruth
authors.initials: R
authors.lastname: Wirawan
authors.forename: Michael
authors.initials: M
authors.lastname: Chikindas
authors.forename: Paul A S
authors.initials: PA
authors.lastname: Breslin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Hoffman
authors.forename: Loredana
authors.initials: L
authors.lastname: Quadro
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000378:metabolism; D004885:Erwinia / Q000201:enzymology* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D051232:Geranylgeranyl-Diphosphate Geranylgeranyltransferase / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D019753:Intramolecular Lyases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D019936:Probiotics; D014801:Vitamin A / Q000096:biosynthesis*; D014802:Vitamin A Deficiency / Q000378:metabolism / Q000382:microbiology / Q000628:therapy*; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D019207:beta Carotene; D014801:Vitamin A; D002338:Carotenoids; D010088:Oxidoreductases; C022398:phytoene dehydrogenase; D050559:beta-Carotene 15,15'-Monooxygenase; D051232:Geranylgeranyl-Diphosphate Geranylgeranyltransferase; D019753:Intramolecular Lyases; C070925:lycopene cyclase-isomerase