A novel pathway of levodopa metabolism by commensal Bifidobacteria.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
06 11 2023
06 11 2023
Historique:
received:
16
08
2023
accepted:
26
10
2023
medline:
8
11
2023
pubmed:
7
11
2023
entrez:
6
11
2023
Statut:
epublish
Résumé
The gold-standard treatment for Parkinson's disease is levodopa (L-DOPA), which is taken orally and absorbed intestinally. L-DOPA must reach the brain intact to exert its clinical effect; peripheral metabolism by host and microbial enzymes is a clinical management issue. The gut microbiota is altered in PD, with one consistent and unexplained observation being an increase in Bifidobacterium abundance among patients. Recently, certain Bifidobacterium species were shown to have the ability to metabolize L-tyrosine, an L-DOPA structural analog. Using both clinical cohort data and in vitro experimentation, we investigated the potential for commensal Bifidobacteria to metabolize this drug. In PD patients, Bifidobacterium abundance was positively correlated with L-DOPA dose and negatively with serum tyrosine concentration. In vitro experiments revealed that certain species, including B. bifidum, B. breve, and B. longum, were able to metabolize this drug via deamination followed by reduction to the compound 3,4-dihydroxyphenyl lactic acid (DHPLA) using existing tyrosine-metabolising genes. DHPLA appears to be a waste product generated during regeneration of NAD +. This metabolism occurs at low levels in rich medium, but is significantly upregulated in nutrient-limited minimal medium. Discovery of this novel metabolism of L-DOPA to DHPLA by a common commensal may help inform medication management in PD.
Identifiants
pubmed: 37932328
doi: 10.1038/s41598-023-45953-z
pii: 10.1038/s41598-023-45953-z
pmc: PMC10628163
doi:
Substances chimiques
Levodopa
46627O600J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19155Subventions
Organisme : CIHR
ID : FDN-159935
Pays : Canada
Informations de copyright
© 2023. The Author(s).
Références
J Neurol. 2010 Nov;257(Suppl 2):S253-61
pubmed: 21080186
Front Microbiol. 2016 Jun 28;7:979
pubmed: 27446020
Parkinsonism Relat Disord. 2016 Nov;32:66-72
pubmed: 27591074
J Pharm Sci. 1981 Jul;70(7):730-3
pubmed: 7264915
Gastroenterology. 2010 Dec;139(6):2102-2112.e1
pubmed: 20600016
Biochem Biophys Res Commun. 1985 Nov 27;133(1):134-9
pubmed: 3907634
Can J Neurol Sci. 1999 Aug;26 Suppl 2:S34-8
pubmed: 10451758
Parkinsonism Relat Disord. 2022 Jan;94:1-9
pubmed: 34844021
Environ Microbiol. 2018 Dec 16;:
pubmed: 30556271
Arch Microbiol. 2021 Dec 28;204(1):91
pubmed: 34962581
PLoS One. 2009 Nov 17;4(11):e7864
pubmed: 19924225
Food Chem. 2017 Aug 1;228:374-380
pubmed: 28317737
Front Neurol. 2014 Dec 15;5:242
pubmed: 25566170
Int J Food Microbiol. 1999 Dec 1;53(1):33-41
pubmed: 10598112
BMC Biol. 2020 Oct 20;18(1):137
pubmed: 33076930
J Dairy Sci. 2001 May;84(5):1011-9
pubmed: 11384026
Mov Disord. 2010 Nov 15;25(15):2649-53
pubmed: 21069833
NPJ Parkinsons Dis. 2019 Nov 29;5:28
pubmed: 31815177
Br J Nutr. 2011 Mar;105(5):755-64
pubmed: 20974015
Genome Biol. 2014;15(12):550
pubmed: 25516281
Appl Environ Microbiol. 2000 Sep;66(9):4084-90
pubmed: 10966432
Nat Microbiol. 2021 Nov;6(11):1367-1382
pubmed: 34675385
Science. 2019 Jun 14;364(6445):
pubmed: 31196984
Mov Disord. 2007 Jan;22(1):41-7
pubmed: 17115387
Neurogastroenterol Motil. 2011 Dec;23(12):1132-9
pubmed: 21988661
Genome Med. 2017 Apr 28;9(1):39
pubmed: 28449715
Mov Disord. 2017 May;32(5):739-749
pubmed: 28195358
Nucleic Acids Res. 2007 Jan;35(Database issue):D521-6
pubmed: 17202168
Lancet. 2015 Aug 29;386(9996):896-912
pubmed: 25904081
Parkinsonism Relat Disord. 2020 Jul;76:63-71
pubmed: 32461054
Nat Commun. 2019 Jan 18;10(1):310
pubmed: 30659181
Biosci Biotechnol Biochem. 2013;77(6):1299-302
pubmed: 23748762
J Parkinsons Dis. 2019;9(s2):S297-S312
pubmed: 31498131
Microb Pathog. 2021 Nov;160:105187
pubmed: 34530073
J Bacteriol. 1999 Mar;181(6):1739-47
pubmed: 10074065
Curr Neuropharmacol. 2018;16(8):1239-1252
pubmed: 28494719
Neurogastroenterol Motil. 2014 Apr;26(4):510-20
pubmed: 24372793
Clin Pharmacol Ther. 1972 Jul-Aug;13(4):584-94
pubmed: 5042372
J Bacteriol. 1981 Jan;145(1):266-71
pubmed: 7007315
Neurotherapeutics. 2020 Oct;17(4):1339-1365
pubmed: 32761324
Mov Disord. 2018 Jan;33(1):88-98
pubmed: 28843021
Mov Disord. 2020 Jul;35(7):1208-1217
pubmed: 32357258