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Gut bacterial deamination of residual levodopa medication for Parkinson’s disease
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Abstract
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Gastrointestinal tract dysfunction is one of the non-motor features, where constipation is reported as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting considerable attention due to their impact on gut homeostasis and host’s physiology. In particular, Clostridium sporogenes is a key contributor to the production of these bioactive metabolites in the human gut. Results: Here, we show that C. sporogenes deaminates levodopa, the main treatment in Parkinson’s disease, and identify the aromatic aminotransferase responsible for the initiation of the deamination pathway. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl)propionic acid, elicits an inhibitory effect on ileal motility in an ex vivo model. We detected 3-(3,4-dihydroxyphenyl)propionic acid in fecal samples of Parkinson’s disease patients on levodopa medication and found that this metabolite is actively produced by the gut microbiota in those stool samples. Conclusions: Levodopa is deaminated by the gut bacterium C. sporogenes producing a metabolite that inhibits ileal motility ex vivo. Overall, this study underpins the importance of the metabolic pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of medication.
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Citations
Cites
A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites
Dodd, D., Spitzer, M. H., Van Treuren, W., Merrill, B. D., Hryckowian, A. J., Higginbottom, S. K., Le, A., Cowan, T. M., Nolan, G. P., Fischbach, M. A., et al. (2017) · Nature · doi:10.1038/nature24661 · Cited by 1,425
Colonic bacterial composition in Parkinson's disease
Keshavarzian, A., Green, S. J., Engen, P. A., Voigt, R. M., Naqib, A., Forsyth, C. B., Mutlu, E., & Shannon, K. M. (2015) · Movement Disorders · doi:10.1002/mds.26307 · Cited by 1,281
Self-citationDiscovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism
Maini Rekdal, V., Bess, E. N., Bisanz, J. E., Turnbaugh, P. J., & Balskus, E. P. (2019) · Science · doi:10.1126/science.aau6323 · Cited by 753
Predicting and Manipulating Cardiac Drug Inactivation by the Human Gut Bacterium Eggerthella lenta
Haiser, H. J., Gootenberg, D. B., Chatman, K., Sirasani, G., Balskus, E. P., & Turnbaugh, P. J. (2013) · Science · doi:10.1126/science.1235872 · Cited by 704
van Kessel, S. P., Frye, A. K., El-Gendy, A. O., Castejon, M., Keshavarzian, A., van Dijk, G., & El Aidy, S. (2019) · Nature Communications · doi:10.1038/s41467-019-08294-y · Cited by 521
Self-citationA modular system for Clostridium shuttle plasmids
Heap, J. T., Pennington, O. J., Cartman, S. T., & Minton, N. P. (2009) · Journal of Microbiological Methods · doi:10.1016/j.mimet.2009.05.004 · Cited by 489
The end products of the metabolism of aromatic amino acids by Clostridia
Elsden, S. R., Hilton, M. G., & Waller, J. M. (1976) · Archives of Microbiology · doi:10.1007/bf00425340 · Cited by 396
High temporal and inter‐individual variation detected in the human ileal microbiota
Booijink, C. C. G. M., El‐Aidy, S., Rajilić‐Stojanović, M., Heilig, H. G. H. J., Troost, F. J., Smidt, H., Kleerebezem, M., De Vos, W. M., & Zoetendal, E. G. (2010) · Environmental Microbiology · doi:10.1111/j.1462-2920.2010.02294.x · Cited by 324 · cited 1×
“Studies on asymptomatic ileostomy subjects established that the core ileal microbiota consists of (facultative) anaerobes including species from Clostridium Cluster I (Booijink et al., 2010; Zoetendal et al., 2012).”
BackgroundDickert, S., Pierik, A. J., & Buckel, W. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.02867.x · Cited by 61 · cited 4×
“Only a slight production of 4-HPPA (from tyrosine) is observed after 48 h, presumably because of the substitution of FldABC by the similar HadABC proteins from the had-operon in C. sporogenes (Dickert et al., 2002; Dodd et al., 2017).”
BackgroundMethodInfluential
Research works printed but not linked: 38
- Donia MS, Fischbach MA. Small molecules from the human microbiota. Science. 2015;349:1254766. https://doi.org/10.1126/science.1254766. · DOI · Paper page
- Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci. 2010;107:228–33. https://doi.org/10.1073/pnas.0906112107. · DOI · Paper page
- Schiering C, Wincent E, Metidji A, Iseppon A, Li Y, Potocnik AJ, et al. Feedback control of AHR signalling regulates intestinal immunity. Nature. 2017;542:242–5. https://doi.org/10.1038/nature21080. · DOI
- Yano JM, Yu K, Mazmanian SK, Hsiao Correspondence EY, Donaldson GP, Shastri GG, et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. 2015;161:264–76. https://doi.org/10.1016/j.cell.2015.02.047. · DOI · Paper page
- Bhattarai Y, Williams BB, Battaglioli EJ, Whitaker WR, Till L, Grover M, et al. Gut microbiota-produced tryptamine activates an epithelial G-protein-coupled receptor to increase colonic secretion. Cell Host Microbe. 2018;23:775–85.e5. https://doi.org/10.1016/j.chom.2018.05.004. · DOI · Paper page
- Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and toll-like receptor 4. Immunity. 2014;41:296–310. https://doi.org/10.1016/j.immuni.2014.06.014. · DOI · Paper page
- Barker HA. Amino acid degradation by anaerobic bacteria. Annu Rev Biochem. 1981;50:23–40. https://doi.org/10.1146/annurev.bi.50.070181.000323. · DOI
- Yvon M, Thirouin S, Rijnen L, Fromentier D, Gripon J. An aminotransferase from Lactococcus lactis initiates conversion of amino acids to cheese flavor compounds. Appl Envir Microbiol. 1997;63:414–9. https://doi.org/10.1128/AEM.63.2.414-419.1997. · DOI · Paper page
- Nierop Groot MN, De Bont JAM. Conversion of phenylalanine to benzaldehyde initiated by an aminotransferase in Lactobacillus plantarum. Appl Environ Microbiol. 1998;64:3009–13. https://doi.org/10.1128/AEM.64.8.3009-3013.1998. · DOI
- Dickert S, Pierik AJ, Linder D, Buckel W. The involvement of coenzyme A esters in the dehydration of (R)-phenyllactate to (E)-cinnamate by Clostridium sporogenes. Eur J Biochem. 2000;267:3874–84. https://doi.org/10.1046/j.1432-1327.2000.01427.x. · DOI
- Bianchine JR, Messiha FS, Hsu TH. Peripheral aromatic L-amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of L-2- 14 C-dopa. Clin Pharmacol Ther. 1972;13:584–94. https://doi.org/10.1002/cpt1972134584. · DOI
- Morgan JP. Metabolism of levodopa in patients with Parkinson’s disease. Arch Neurol. 1971;25:39. https://doi.org/10.1001/archneur.1971.00490010049007. · DOI
- Sasahara K, Nitanai T, Habara T, Kojima T, Kawahara Y, Morioka T, et al. Dosage form design for improvement of bioavailability of levodopa IV: possible causes of low bioavailability of oral levodopa in dogs. J Pharm Sci. 1981;70:730–3. https://doi.org/10.1002/jps.2600700705. · DOI
- Goldin BR, Peppercorn MA, Goldman P. Contributions of host and intestinal microflora in the metabolism of L-dopa by the rat. J Pharmacol Exp Ther. 1973;186:160–6.
- Fasano A, Visanji NP, Liu LWC, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol. 2015;14:625–39. https://doi.org/10.1016/S1474-4422(15)00007-1. · DOI · Paper page
- Panagamuwa B, Kumar D, Ortiz J, Keighley MRB. Motor abnormalities in the terminal ileum of patients with chronic idiopathic constipation. Br J Surg. 1994;81:1685–8. https://doi.org/10.1002/bjs.1800811142. · DOI
- Van Der Sijp JRM, Kamm MA, Nightingale JMD, Britton KE, Granowska M, Mather SJ, et al. Disturbed gastric and small bowel transit in severe idiopathic constipation. Dig Dis Sci. 1993;38:837–44. https://doi.org/10.1007/BF01295909. · DOI
- Dutkiewicz J, Szlufik S, Nieciecki M, Charzyńska I, Królicki L, Smektała P, et al. Small intestine dysfunction in Parkinson’s disease. J Neural Transm. 2015;122:1659–61. https://doi.org/10.1007/s00702-015-1442-0. · DOI
- Knudsen K, Haase AM, Fedorova TD, Bekker AC, Ostergaard K, Krogh K, et al. Gastrointestinal transit time in Parkinson’s disease using a magnetic tracking system. J Parkinsons Dis. 2017;7:471–9. https://doi.org/10.3233/JPD-171131. · DOI
- Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett. 2004;150:111–22. https://doi.org/10.1016/j.toxlet.2003.12.070. · DOI
- Heap JT, Kuehne SA, Ehsaan M, Cartman ST, Cooksley CM, Scott JC, et al. The ClosTron: mutagenesis in Clostridium refined and streamlined. J Microbiol Methods. 2010;80:49–55. https://doi.org/10.1016/j.mimet.2009.10.018. · DOI · Paper page
- Roager HM, Hansen LBS, Bahl MI, Frandsen HL, Carvalho V, Gøbel RJ, et al. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat Microbiol. 2016;1:16093. https://doi.org/10.1038/nmicrobiol.2016.93. · DOI · Paper page
- Iwamoto K, Watanabe J, Yamada M, Atsumi F, Matsushita T. Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats. J Pharm Pharmacol. 1987;39:421–5. https://doi.org/10.1111/j.2042-7158.1987.tb03413.x. · DOI
- Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CC, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates. ISME J. 2012;6:1415–26. https://doi.org/10.1038/ismej.2011.212. · DOI · Paper page
- Costa M, Brookes SJ, Hennig GW. Anatomy and physiology of the enteric nervous system. Gut. 2000;47(Suppl 4):iv15–9; discussion iv26. https://doi.org/10.1136/gut.47.suppl_4.iv15. · DOI
- Ringdahl B. Dissociation constants and relative efficacies of acetylcholine, (+)- and (-)-methacholine at muscarinic receptors in the guinea-pig ileum. Br J Pharmacol. 1986;89:7–13. https://doi.org/10.1111/j.1476-5381.1986.tb11115.x. · DOI
- Jenner AM, Rafter J, Halliwell B. Human fecal water content of phenolics: the extent of colonic exposure to aromatic compounds. Free Radic Biol Med. 2005;38:763–72. https://doi.org/10.1016/j.freeradbiomed.2004.11.020. · DOI · Paper page
- Jin JS, Hattori M. Isolation and characterization of a human intestinal bacterium Eggerthella sp. CAT-1 capable of cleaving the C-Ring of (+)-catechin and (-)-Epicatechin, followed by p-dehydroxylation of the B-ring. Biol Pharm Bull. 2012;35:2252–6. · DOI
- Kalia VC, Mukherjee T, Bhushan A, Joshi J, Shankar P, Huma N. Analysis of the unexplored features of rrs (16S rDNA) of the genus Clostridium. BMC Genomics. 2011;12. https://doi.org/10.1186/1471-2164-12-18. · DOI
- Niehues M, Hensel A. In-vitro interaction of L-dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability? J Pharm Pharmacol. 2009;61:1303–7. https://doi.org/10.1211/jpp/61.10.0005. · DOI
- Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science. 2019;363:eaat9931. https://doi.org/10.1126/science.aat9931. · DOI · Paper page
- Williams BB, Van Benschoten AH, Cimermancic P, Donia MS, Zimmermann M, Taketani M, et al. Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine. Cell Host Microbe. 2014;16:495–503. https://doi.org/10.1016/j.chom.2014.09.001. · DOI · Paper page
- Lucchelli A, Boselli C, Grana E. Dopamine-induced relaxation of the guinea-pig isolated jejunum is not mediated through dopamine receptors. Pharmacol Res. 1990;22:433–44. https://doi.org/10.1016/1043-6618(90)90750-8. · DOI
- Heap JT, Pennington OJ, Cartman ST, Carter GP, Minton NP. The ClosTron: a universal gene knock-out system for the genus Clostridium 2007;70:452–464. doi:https://doi.org/10.1016/j.mimet.2007.05.021. · DOI · Paper page
- Williams DR, Young DI, Young M. Conjugative plasmid transfer from Escherichia coli to Clostridium acetobutylicum. J Gen Microbiol. 1990;136:819–26. https://doi.org/10.1099/00221287-136-5-819. · DOI
- Nagatsu T, Kojima K. Application of electrochemical detection in high-performance liquid chromatography to the assay of biologically active compounds. TrAC Trends Anal Chem. 1988;7:21–7. https://doi.org/10.1016/0165-9936(88)80026-8. · DOI
- Wood DE, Lu J, Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol. 2019;20:1–13. https://doi.org/10.1186/s13059-019-1891-0. · DOI
- Lu J, Breitwieser FP, Thielen P, Salzberg SL. Bracken: estimating species abundance in metagenomics data. PeerJ Comput Sci. 2017;2017:1–17. https://doi.org/10.7717/peerj-cs.104. · DOI
Cited by
Varesi, A., Campagnoli, L. I. M., Fahmideh, F., Pierella, E., Romeo, M., Ricevuti, G., Nicoletta, M., Chirumbolo, S., & Pascale, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232012289 · Cited by 88
van Kessel, S. P., Bullock, A., van Dijk, G., & El Aidy, S. (2022) · mSystems · doi:10.1128/msystems.01191-21 · Cited by 41
van Kessel, S. P., Auvinen, P., Scheperjans, F., & El Aidy, S. (2021) · npj Parkinson s Disease · doi:10.1038/s41531-021-00260-0 · Cited by 34
A review of studies on gut microbiota and levodopa metabolism
Zhong, Z., Ye, M., & Yan, F. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1046910 · Cited by 31
Metadata
- Authors
- van Kessel, S. P., de Jong, H. R., Winkel, S. L., van Leeuwen, S. S., Nelemans, S. A., Permentier, H., Keshavarzian, A., & El Aidy, S.
- Venue
- BMC Biology
- Published
- 2020-10-20
- Volume
- 18
- Issue
- 1
- ISSN
- 1741-7007
- Cited by
- 56
- References
- 9
- Language
- en
- Licence
- creativecommons.org/licenses/by/4.0 (tdm)
- creativecommons.org/licenses/by/4.0 (vor)
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