Relationship Between Gut Bacteria and Levodopa Metabolism

Ahlskog, J.E.; Muenter, M.D. Frequency of levodopa‐related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov. Disord., 2001, 16(3), 448-458.
[http://dx.doi.org/10.1002/mds.1090] [PMID: 11391738]

Fahn, S. Description of Parkinson’s disease as a clinical syndrome. Ann. N. Y. Acad. Sci., 2003, 991(1), 1-14.
[http://dx.doi.org/10.1111/j.1749-6632.2003.tb07458.x] [PMID: 12846969]

Manson, A.; Stirpe, P.; Schrag, A. Levodopa-induced-dyskinesias clinical features, incidence, risk factors, management and impact on quality of life. J. Parkinsons Dis., 2012, 2(3), 189-198.
[http://dx.doi.org/10.3233/JPD-2012-120103] [PMID: 23938226]

Perez-Lloret, S.; Negre-Pages, L.; Damier, P.; Delval, A.; Derkinderen, P.; Destée, A.; Meissner, W.G.; Tison, F.; Rascol, O. LDOPA-induced dyskinesias, motor fluctuations and health-related quality of life: the COPARK survey. Eur. J. Neurol., 2017, 24(12), 1532-1538.
[http://dx.doi.org/10.1111/ene.13466] [PMID: 28940893]

Papavasiliou, P.S.; Cotzias, G.C.; Düby, S.E.; Steck, A.J.; Fehling, C.; Bell, M.A. Levodopa in Parkinsonism: potentiation of central effects with a peripheral inhibitor. N. Engl. J. Med., 1972, 286(1), 8-14.
[http://dx.doi.org/10.1056/NEJM197201062860102] [PMID: 4550085]

Fasano, A.; Bove, F.; Gabrielli, M.; Petracca, M.; Zocco, M.A.; Ragazzoni, E.; Barbaro, F.; Piano, C.; Fortuna, S.; Tortora, A.; Di Giacopo, R.; Campanale, M.; Gigante, G.; Lauritano, E.C.; Navarra, P.; Marconi, S.; Gasbarrini, A.; Bentivoglio, A.R. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov. Disord., 2013, 28(9), 1241-1249.
[http://dx.doi.org/10.1002/mds.25522] [PMID: 23712625]

Hashim, H.; Azmin, S.; Razlan, H.; Yahya, N.W.; Tan, H.J.; Manaf, M.R.A.; Ibrahim, N.M. Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson’s disease. PLoS One, 2014, 9(11), e112330-e112330.
[http://dx.doi.org/10.1371/journal.pone.0112330] [PMID: 25411976]

Qin, J.; Li, R.; Raes, J.; Arumugam, M.; Burgdorf, K.S.; Manichanh, C.; Nielsen, T.; Pons, N.; Levenez, F.; Yamada, T.; Mende, D.R.; Li, J.; Xu, J.; Li, S.; Li, D.; Cao, J.; Wang, B.; Liang, H.; Zheng, H.; Xie, Y.; Tap, J.; Lepage, P.; Bertalan, M.; Batto, J.M.; Hansen, T.; Le Paslier, D.; Linneberg, A.; Nielsen, H.B.; Pelletier, E.; Renault, P.; Sicheritz-Ponten, T.; Turner, K.; Zhu, H.; Yu, C.; Li, S.; Jian, M.; Zhou, Y.; Li, Y.; Zhang, X.; Li, S.; Qin, N.; Yang, H.; Wang, J.; Brunak, S.; Doré, J.; Guarner, F.; Kristiansen, K.; Pedersen, O.; Parkhill, J.; Weissenbach, J.; Bork, P.; Ehrlich, S.D.; Wang, J. A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 2010, 464(7285), 59-65.
[http://dx.doi.org/10.1038/nature08821] [PMID: 20203603]

Yano, J.M.; Yu, K.; Donaldson, G.P.; Shastri, G.G.; Ann, P.; Ma, L.; Nagler, C.R.; Ismagilov, R.F.; Mazmanian, S.K.; Hsiao, E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 2015, 161(2), 264-276.
[http://dx.doi.org/10.1016/j.cell.2015.02.047] [PMID: 25860609]

Mao, K.; Baptista, A.P.; Tamoutounour, S.; Zhuang, L.; Bouladoux, N.; Martins, A.J.; Huang, Y.; Gerner, M.Y.; Belkaid, Y.; Germain, R.N. Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism. Nature, 2018, 554(7691), 255-259.
[http://dx.doi.org/10.1038/nature25437] [PMID: 29364878]

Pusceddu, M.M.; El Aidy, S.; Crispie, F.; O’Sullivan, O.; Cotter, P.; Stanton, C.; Kelly, P.; Cryan, J.F.; Dinan, T.G. N-3 Polyunsaturated Fatty Acids (PUFAs) Reverse the Impact of Early-Life Stress on the Gut Microbiota. PLoS One, 2015, 10(10), e0139721-e0139721.
[http://dx.doi.org/10.1371/journal.pone.0139721] [PMID: 26426902]

El Aidy, S.; van Baarlen, P.; Derrien, M.; Lindenbergh-Kortleve, D.J.; Hooiveld, G.; Levenez, F.; Doré, J.; Dekker, J.; Samsom, J.N.; Nieuwenhuis, E.E.S.; Kleerebezem, M. Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice. Mucosal Immunol., 2012, 5(5), 567-579.
[http://dx.doi.org/10.1038/mi.2012.32] [PMID: 22617837]

Kelly, J.R.; Borre, Y.; O’ Brien, C.; Patterson, E.; El Aidy, S.; Deane, J.; Kennedy, P.J.; Beers, S.; Scott, K.; Moloney, G.; Hoban, A.E.; Scott, L.; Fitzgerald, P.; Ross, P.; Stanton, C.; Clarke, G.; Cryan, J.F.; Dinan, T.G. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. J. Psychiatr. Res., 2016, 82, 109-118.
[http://dx.doi.org/10.1016/j.jpsychires.2016.07.019] [PMID: 27491067]

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(10), 1303-1307.
[http://dx.doi.org/10.1211/jpp/61.10.0005] [PMID: 19814861]

Enright, E.F.; Gahan, C.G.; Joyce, S.A.; Griffin, B.T. The impact of the gut microbiota on drug metabolism and clinical outcome. Yale J. Biol. Med., 2016, 89(3), 375-382.
[PMID: 27698621]

Hsu, A.; Yao, H.M.; Gupta, S.; Modi, N.B. Comparison of the pharmacokinetics of an oral extended‐release capsule formulation of carbidopa‐levodopa (IPX066) with immediate‐release carbidopa‐levodopa (Sinemet®), sustained‐release carbidopa‐levodopa (Sinemet® CR), and carbidopa‐levodopa‐entacapone (Stalevo®). J. Clin. Pharmacol., 2015, 55(9), 995-1003.
[http://dx.doi.org/10.1002/jcph.514] [PMID: 25855267]

Longo, D.M.; Yang, Y.; Watkins, P.B.; Howell, B.A.; Siler, S.Q. Elucidating differences in the hepatotoxic potential of tolcapone and entacapone with DILIsym®, a mechanistic model of drug‐induced liver injury. CPT Pharmacometrics Syst. Pharmacol., 2016, 5(1), 31-39.
[http://dx.doi.org/10.1002/psp4.12053] [PMID: 26844013]

Gray, R.; Patel, S.; Ives, N.; Rick, C.; Woolley, R.; Muzerengi, S.; Gray, A.; Jenkinson, C.; McIntosh, E.; Wheatley, K.; Williams, A.; Clarke, C.E.; Young, K.; Price, H.; Price, J.; Lambert, A.; Reeve, R.; Sewell, M.; Broome, S.; Williams, A.; Baker, M.; Clarke, C.; Fitzpatrick, R.; Gray, A.; Greenhall, R.; Jenkinson, C.; Mant, D.; McIntosh, E.; Sandercock, P.; Baugent, C.; Crome, P.; Au, P.; Boodell, T.; Cheed, V.C.; Daniels, J.; Dowling, F.; Evans, L.; Hawker, R.; Kaur, S.; Rick, C.; Wheatley, K.; Winkles, N.; Hingley, D.; Sturdy, L.; Wooley, R.; Ottridge, R.; Peto, L.; Hilken, N.; Counsell, C.; Caie, L.; Caslake, R.; Coleman, R.; Crowley, P.; Gerrie, L.; Gordon, J.; Harris, C.; Leslie, V.; MacLeod, M.A.; Taylor, K.; Worth, P.; Barker, R.A.; Forsyth, D.; Halls, M.; Young, J.; Phillips, W.; Manford, M.; Thangarajah, N.; Blake, D.; Prescott, R.; Carr, P.; Cochrane, L.; Rose, A.; McLaren, A.; Drover, M.; Karunaratne, P.; Eady, A.; Wislocka-Kryjak, M.; Ghaus, N.; Grueger, A.; Mallinson, B.; Wihl, G.; Ballantyne, S.; Hutchinson, S.; Lewthwaite, A.; Nicholl, D.; Ritch, A.; Coyle, S.; Hornabrook, R.; Irfan, H.; Poxon, S.; Nath, U.; Davison, J.; Dodds, S.; Robinson, G.; Gray, C.; Fletcher, P.; Morrow, P.; Sliva, M.; Folkes, E.; Gilbert, A.; Hayes, H.; Burrows, E.; Donaldson, S.; Lawrence, J.; Rhind, G.; Baxter, G.; Bell, J.; Gorman, J.; Guptha, S.; Noble, C.; Hindle, J.; Jones, S.; Ohri, P.; Subashchandran, R.; Roberts, E.; Raw, J.; Wadhwa, U.; Aspden, L.; Partington, L.; Vanek, H.; Whone, A.; Barber, R.; Haywood, B.; Heywood, P.; Lewis, H.; O’Sullivan, K.; Prout, K.; Whelan, L.; Medcalf, P.; Sliva, M.; Fuller, G.; Morrish, P.; Wales, E.; Dalziel, J.; Overstall, P.; Bouifraden, K.; Evans, C.; Ward, G.; Matheson, P.; Lockington, T.; Graham, A.; Grimmer, S.F.M.; Sheehan, L.J.; Williams, H.; Hubbard, I.; Walters, R.; Glasspool, R.; Critchley, P.; Abbott, R.; Kendall, B.; Lawden, M.; Lo, N.; Rajaally, Y.; Simpson, B.; Martey, J.; Wray, L.G.; Omar, M.; Sharma, A.; Gale, A.; Phirii, D.; Sekaran, L.; Wijayasiri, S.; Silverdale, M.; Walker, D.; Fleary, H.; Monaghan, A.; Senthil, V.; Reynolds, S.; Chong, M.S.; Diem, D.; Kundu, B.; Arnold, D.; Quinn, N.; Benamer, H.; Billings, J.; Corston, R.; D’Costa, D.; Green, M.; Shuri, J.; Noble, J.M.; Cassidy, T.; Gani, A.; Lawson, R.; Nirubin, A.; Cochius, J.; Dick, D.; Lee, M.; Payne, B.; Roche, M.; Sabanathan, K.; Shields, S.; Hipperson, M.; Reading, F.; Saunders, J.; Harper, G.; Honan, W.; Gill, L.; Stanley, J.; Vernon, N.; Skinner, A.; McCann, P.; Walker, R.; Edmonds, P.; O’Hanlon, S.; Wood, B.; Hand, A.; Robinson, L.; Liddle, J.; Bolam, D.; Raha, S.; Ebebezer, L.; Thompson, S.; Pall, H.; Praamstra, P.; Crouch, R.; Healy, K.; Johnson, M.; Jenkinson, M.; Abdel-Hafiz, A.; Al-Modaris, F.; Dutta, S.; Mallik, T.; Mondal, B.; Roberts, J.; Sinha, S.; Amar, K.; Atkins, S.; Devadason, G.; Martin, A.; Cox, C.; Malone, T.; Fenwick, G.; Gormley, K.; Gutowski, N.; Harris, S.; Harrower, T.; Hemsley, A.; James, M.; Jeffreys, M.O.; Pearce, V.; Sheridan, R.; Sword, J.; Zeman, A.; Soper, C.; Vassallo, J.; Bennett, J.; Lyell, V.; Robertson, D.; Howcroft, D.; Mugweni, K.; Stephens, A.; Whelan, E.; Wright, A.; Chamberlain, J.; Padiachy, D.; Marigold, J.; Lee, J.; Roberts, H.; Adams, J.; Dulay, J.; Evans, S.; Frankel, J.; Gove, R.; Turner, G.; Mallik, N.; McElwaine, T.; Morgan, S.; Phipps, H.; Pressly, V.; Queen, V.; Tan, R.; Grossett, D.; Macphee, G.; Vennard, C.; Rektorova, I.; Dhakam, Z.; Carey, G.; Castledon, B.; Sunderland, C.; Kalcantera, E.; Long, C.; Mandal, B.; Martin, V.; Nari, R.; Nicholas, V.; Moffitt, V.; Hammans, S.; Rice-Oxley, M.; Webb, J.; Franks, S.; Cooper, S.; Hussain, M.; Solanki, T.; Darch, W.; Homan, J.; Sharratt, D.; Griggs, G.; Kendall, G.; Ford, A.; Stocker, K.; Strens, L.; Grubneac, A.; Ponsford, J.; Teare, L.; Moore, A.P.; O’Brien, I.; Watling, D.; Wyatt, L.; Rizvi, S.; Walker, E.; Berry, G.; Russell, N.; Rashed, K.; Baker, K.; Qadiri, M.R.; Buckley, C.; Bulley, S.; Gibbons, D.; Goodland, R.; Heywood, P.; Jones, L.; Martin, L.; Rowland-Axe, R.; Stone, A.; Whittuck, M.R. Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy. JAMA Neurol., 2022, 79(2), 131-140.
[http://dx.doi.org/10.1001/jamaneurol.2021.4736] [PMID: 34962574]

van Kessel, S.P.; Frye, A.K.; El-Gendy, A.O.; Castejon, M.; Keshavarzian, A.; van Dijk, G.; El Aidy, S. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nat. Commun., 2019, 10(1), 310.
[http://dx.doi.org/10.1038/s41467-019-08294-y] [PMID: 30659181]

Zhang, K.; Ni, Y. Tyrosine decarboxylase from Lactobacillus brevis: Soluble expression and characterization. Protein Expr. Purif., 2014, 94, 33-39.
[http://dx.doi.org/10.1016/j.pep.2013.10.018] [PMID: 24211777]

Perez, M.; Calles-Enríquez, M.; Nes, I.; Martin, M.C.; Fernandez, M.; Ladero, V.; Alvarez, M.A. Tyramine biosynthesis is transcriptionally induced at low pH and improves the fitness of Enterococcus faecalis in acidic environments. Appl. Microbiol. Biotechnol., 2015, 99(8), 3547-3558.
[http://dx.doi.org/10.1007/s00253-014-6301-7] [PMID: 25529314]

Adibi, S.A.; Mercer, D.W. Protein digestion in human intestine as reflected in luminal, mucosal, and plasma amino acid concentrations after meals. J. Clin. Invest., 1973, 52(7), 1586-1594.
[http://dx.doi.org/10.1172/JCI107335] [PMID: 4718954]

Abrams, W.B.; Coutinho, C.B.; Leon, A.S.; Spiegel, H.E. Absorption and metabolism of levodopa. JAMA, 1971, 218(13), 1912-1914.
[http://dx.doi.org/10.1001/jama.1971.03190260028007] [PMID: 5171067]

Maini, R.V.; Bess, E.N.; Bisanz, J.E.; Turnbaugh, P.J.; Balskus, E.P. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science, 2019, 364(6445), eaau6323.
[http://dx.doi.org/10.1126/science.aau6323] [PMID: 31196984]

Whitfield, A.C.; Moore, B.T.; Daniels, R.N. Classics in chemical neuroscience: levodopa. ACS Chem. Neurosci., 2014, 5(12), 1192-1197.
[http://dx.doi.org/10.1021/cn5001759] [PMID: 25270271]

Bisanz, J.E.; Soto-Perez, P.; Lam, K.N.; Bess, E.N.; Haiser, H.J.; Allen-Vercoe, E.; Rekdal, V.M.; Balskus, E.P.; Turnbaugh, P.J. Illuminating the microbiome’s dark matter: a functional genomic toolkit for the study of human gut Actinobacteria. bioRxiv, 2018.
[http://dx.doi.org/10.1101/304840]

Martínez-del Campo, A.; Bodea, S.; Hamer, H.A.; Marks, J.A.; Haiser, H.J.; Turnbaugh, P.J.; Balskus, E.P. Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria. MBio, 2015, 6(2), e00042-15.
[http://dx.doi.org/10.1128/mBio.00042-15] [PMID: 25873372]

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. Gut bacterial deamination of residual levodopa medication for Parkinson’s disease. BMC Biol., 2020, 18(1), 137.
[http://dx.doi.org/10.1186/s12915-020-00876-3] [PMID: 33076930]

Donia, M.S.; Fischbach, M.A. Small molecules from the human microbiota. Science, 2015, 349(6246), 1254766.
[http://dx.doi.org/10.1126/science.1254766] [PMID: 26206939]

Barker, H.A. Amino acid degradation by anaerobic bacteria. Annu. Rev. Biochem., 1981, 50(1), 23-40.
[http://dx.doi.org/10.1146/annurev.bi.50.070181.000323] [PMID: 6791576]

Yvon, M.; Thirouin, S.; Rijnen, L.; Fromentier, D.; Gripon, J.C. An aminotransferase from Lactococcus lactis initiates conversion of amino acids to cheese flavor compounds. Appl. Environ. Microbiol., 1997, 63(2), 414-419.
[http://dx.doi.org/10.1128/aem.63.2.414-419.1997] [PMID: 9023921]

Nierop Groot, M.N.; de Bont, J.A.M. Conversion of phenylalanine to benzaldehyde initiated by an aminotransferase in lactobacillus plantarum. Appl. Environ. Microbiol., 1998, 64(8), 3009-3013.
[http://dx.doi.org/10.1128/AEM.64.8.3009-3013.1998] [PMID: 9687465]

Elsden, S.R.; Hilton, M.G.; Waller, J.M. The end products of the metabolism of aromatic amino acids by clostridia. Arch. Microbiol., 1976, 107(3), 283-288.
[http://dx.doi.org/10.1007/BF00425340] [PMID: 1275638]

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.; Sonnenburg, J.L. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature, 2017, 551(7682), 648-652.
[http://dx.doi.org/10.1038/nature24661] [PMID: 29168502]

Bansal, T.; Alaniz, R.C.; Wood, T.K.; Jayaraman, A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc. Natl. Acad. Sci. USA, 2010, 107(1), 228-233.
[http://dx.doi.org/10.1073/pnas.0906112107] [PMID: 19966295]

Schiering, C.; Wincent, E.; Metidji, A.; Iseppon, A.; Li, Y.; Potocnik, A.J.; Omenetti, S.; Henderson, C.J.; Wolf, C.R.; Nebert, D.W.; Stockinger, B. Feedback control of AHR signalling regulates intestinal immunity. Nature, 2017, 542(7640), 242-245.
[http://dx.doi.org/10.1038/nature21080] [PMID: 28146477]

Bhattarai, Y.; Williams, B.B.; Battaglioli, E.J.; Whitaker, W.R.; Till, L.; Grover, M.; Linden, D.R.; Akiba, Y.; Kandimalla, K.K.; Zachos, N.C.; Kaunitz, J.D.; Sonnenburg, J.L.; Fischbach, M.A.; Farrugia, G.; Kashyap, P.C. Gut Microbiota-Produced Tryptamine Activates an Epithelial G-Protein-Coupled Receptor to Increase Colonic Secretion. Cell Host Microbe, 2018, 23(6), 775-785.e5.
[http://dx.doi.org/10.1016/j.chom.2018.05.004] [PMID: 29902441]

Venkatesh, M.; Mukherjee, S.; Wang, H.; Li, H.; Sun, K.; Benechet, A.P.; Qiu, Z.; Maher, L.; Redinbo, M.R.; Phillips, R.S.; Fleet, J.C.; Kortagere, S.; Mukherjee, P.; Fasano, A.; Le Ven, J.; Nicholson, J.K.; Dumas, M.E.; Khanna, K.M.; Mani, S. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity, 2014, 41(2), 296-310.
[http://dx.doi.org/10.1016/j.immuni.2014.06.014] [PMID: 25065623]

Morgan, J.P.; Bianchine, J.R.; Spiegel, H.E.; Rivera-Calimlim, L.; Hersey, R.M. Metabolism of levodopa in patients with Parkinson’s disease. Radioactive and fluorometric assays. Arch. Neurol., 1971, 25(1), 39-44.
[http://dx.doi.org/10.1001/archneur.1971.00490010049007] [PMID: 5146410]

Bianchine, J.R.; Messiha, F.S.; Hsu, T.H. Peripheral aromatic L-amino acids decarboxylase inhibitor in parkinsonism. II. Effect on metabolism of L-2-14C-dopa. Clin. Pharmacol. Ther., 1972, 13(4), 584-594.
[http://dx.doi.org/10.1002/cpt1972134584] [PMID: 5042372]

Sasahara, K.; Nitanai, T.; Habara, T.; Kojima, T.; Kawahara, Y.; Morioka, T.; Nakajima, E. 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(7), 730-733.
[http://dx.doi.org/10.1002/jps.2600700705] [PMID: 7264915]

Goldin, B.R.; Peppercorn, M.A.; Goldman, P. Contributions of host and intestinal microflora in the metabolism of L-dopa by the rat. J. Pharmacol. Exp. Ther., 1973, 186(1), 160-166.
[PMID: 4723308]

Dickert, S.; Pierik, A.J.; 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(12), 3874-3884.
[http://dx.doi.org/10.1046/j.1432-1327.2000.01427.x] [PMID: 10849007]

Dickert, S.; Pierik, A.J.; Buckel, W. Molecular characterization of phenyllactate dehydratase and its initiator from Clostridium sporogenes. Mol. Microbiol., 2002, 44(1), 49-60.
[http://dx.doi.org/10.1046/j.1365-2958.2002.02867.x] [PMID: 11967068]

Roager, H.M.; Hansen, L.B.S.; Bahl, M.I.; Frandsen, H.L.; Carvalho, V.; Gøbel, R.J.; Dalgaard, M.D.; Plichta, D.R.; Sparholt, M.H.; Vestergaard, H.; Hansen, T.; Sicheritz-Pontén, T.; Nielsen, H.B.; Pedersen, O.; Lauritzen, L.; Kristensen, M.; Gupta, R.; Licht, T.R. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat. Microbiol., 2016, 1(9), 16093.
[http://dx.doi.org/10.1038/nmicrobiol.2016.93] [PMID: 27562254]

Jin, J.S.; 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(12), 2252-2256.
[http://dx.doi.org/10.1248/bpb.b12-00726] [PMID: 23207778]

Haiser, H.J.; Gootenberg, D.B.; Chatman, K.; Sirasani, G.; Balskus, E.P.; Turnbaugh, P.J. Predicting and manipulating cardiac drug inactivation by the human gut bacterium Eggerthella lenta. Science, 2013, 341(6143), 295-298.
[http://dx.doi.org/10.1126/science.1235872] [PMID: 23869020]

Fasano, A.; Visanji, N.P.; Liu, L.W.C.; Lang, A.E.; Pfeiffer, R.F. Gastrointestinal dysfunction in Parkinson’s disease. Lancet Neurol., 2015, 14(6), 625-639.
[http://dx.doi.org/10.1016/S1474-4422(15)00007-1] [PMID: 25987282]

Panagamuwa, B.; Kumar, D.; Ortiz, J.; Keighley, M.R.B. Motor abnormalities in the terminal ileum of patients with chronic idiopathic constipation. Br. J. Surg., 2005, 81(11), 1685-1688.
[http://dx.doi.org/10.1002/bjs.1800811142] [PMID: 7827908]

Van Der Sijp, J.R.M.; Kamm, M.A.; Nightingale, J.M.D.; Britton, K.E.; Granowska, M.; Mather, S.J.; Akkermans, L.M.A.; Lennard-Jones, J.E. Disturbed gastric and small bowel transit in severe idiopathic constipation. Dig. Dis. Sci., 1993, 38(5), 837-844.
[http://dx.doi.org/10.1007/BF01295909] [PMID: 8482182]

Broadley, K.J. The vascular effects of trace amines and amphetamines. Pharmacol. Ther., 2010, 125(3), 363-375.
[http://dx.doi.org/10.1016/j.pharmthera.2009.11.005] [PMID: 19948186]

Lindemann, L.; Hoener, M.C. A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol. Sci., 2005, 26(5), 274-281.
[http://dx.doi.org/10.1016/j.tips.2005.03.007] [PMID: 15860375]

Nagatsu, T.; Nakashima, A.; Ichinose, H.; Kobayashi, K. Human tyrosine hydroxylase in Parkinson’s disease and in related disorders. J. Neural Transm. (Vienna), 2019, 126(4), 397-409.
[http://dx.doi.org/10.1007/s00702-018-1903-3] [PMID: 29995172]

Hayashi, H.; Mizuguchi, H.; Kagamiyama, H. Rat liver aromatic L-amino acid decarboxylase: Spectroscopic and kinetic analysis of the coenzyme and reaction intermediates. Biochemistry, 1993, 32(3), 812-818.
[http://dx.doi.org/10.1021/bi00054a011] [PMID: 8422386]

Kim; Cho, K.H.; Shin, M.S.; Lee, J.M.; Cho, H.S.; Kim, C.J.; Shin, D.H.; Yang, H.J. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson’s disease. Int. J. Mol. Med., 2014, 33(4), 870-878.
[http://dx.doi.org/10.3892/ijmm.2014.1656] [PMID: 24535622]

Kwon, I.H.; Choi, H.S.; Shin, K.S.; Lee, B.K.; Lee, C.K.; Hwang, B.Y.; Lim, S.C.; Lee, M.K. Effects of berberine on 6-hydroxydopamine-induced neurotoxicity in PC12 cells and a rat model of Parkinson’s disease. Neurosci. Lett., 2010, 486(1), 29-33.
[http://dx.doi.org/10.1016/j.neulet.2010.09.038] [PMID: 20851167]

Wang, Y.; Tong, Q.; Ma, S.R.; Zhao, Z.X.; Pan, L.B.; Cong, L.; Han, P.; Peng, R.; Yu, H.; Lin, Y.; Gao, T.L.; Shou, J.W.; Li, X.Y.; Zhang, X.F.; Zhang, Z.W.; Fu, J.; Wen, B.Y.; Yu, J.B.; Cao, X.; Jiang, J.D. Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota. Signal Transduct. Target. Ther., 2021, 6(1), 77.
[http://dx.doi.org/10.1038/s41392-020-00456-5] [PMID: 33623004]

Feng, R.; Shou, J.W.; Zhao, Z.X.; He, C.Y.; Ma, C.; Huang, M.; Fu, J.; Tan, X.S.; Li, X.Y.; Wen, B.Y.; Chen, X.; Yang, X.Y.; Ren, G.; Lin, Y.; Chen, Y.; You, X.F.; Wang, Y.; Jiang, J.D. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci. Rep., 2015, 5(1), 12155.
[http://dx.doi.org/10.1038/srep12155] [PMID: 26174047]

Kim, H.L.; Park, Y.S. Maintenance of cellular tetrahydrobiopterin homeostasis. BMB Rep., 2010, 43(9), 584-592.
[http://dx.doi.org/10.5483/BMBRep.2010.43.9.584] [PMID: 20846489]

Surwase, S.N.; Jadhav, J.P. Bioconversion of l-tyrosine to l-DOPA by a novel bacterium Bacillus sp. JPJ. Amino Acids, 2011, 41(2), 495-506.
[http://dx.doi.org/10.1007/s00726-010-0768-z] [PMID: 20963458]

Houck, D.R.; Hanners, J.L.; Unkefer, C.J.; van Kleef, M.A.G.; Duine, J.A. PQQ: Biosynthetic studies inMethylobacterium AM1 andHyphomicrobium X using specific13C labeling and NMR. Antonie van Leeuwenhoek, 1989, 56(1), 93-101.
[http://dx.doi.org/10.1007/BF00822589] [PMID: 2549867]

Muñoz, A.J.; Hernández-Chávez, G.; de Anda, R.; Martínez, A.; Bolívar, F.; Gosset, G. Metabolic engineering of Escherichia coli for improving l-3,4-dihydroxyphenylalanine (l-DOPA) synthesis from glucose. J. Ind. Microbiol. Biotechnol., 2011, 38(11), 1845-1852.
[http://dx.doi.org/10.1007/s10295-011-0973-0] [PMID: 21512819]

Connolly, B.S.; Lang, A.E. Pharmacological treatment of Parkinson disease: a review. JAMA, 2014, 311(16), 1670-1683.
[http://dx.doi.org/10.1001/jama.2014.3654] [PMID: 24756517]

Gey, K.F.; Pletscher, A. Distribution and metabolism of DL -3,4-dihydroxy[2-14C]-phenylalanine in rat tissues. Biochem. J., 1964, 92(2), 300-308.
[http://dx.doi.org/10.1042/bj0920300] [PMID: 5838073]

Bergmann, S.; Curzon, G.; Friedel, J.; Godwin-Austen, R.B.; Marsden, C.D.; Parkes, J.D. The absorption and metabolism of a standard oral dose of levodopa in patients with Parkinsonism. Br. J. Clin. Pharmacol., 1974, 1(5), 417-424.
[http://dx.doi.org/10.1111/j.1365-2125.1974.tb00280.x] [PMID: 22454921]

Cotzias, G.C.; Papavasiliou, P.S.; Ginos, J.; Steck, A.; Düby, S. Metabolic modification of Parkinson’s disease and of chronic manganese poisoning. Annu. Rev. Med., 1971, 22(1), 305-326.
[http://dx.doi.org/10.1146/annurev.me.22.020171.001513] [PMID: 4944422]

Goldenberg, M.M. Medical management of Parkinson’s disease. P&T, 2008, 33(10), 590-606.
[PMID: 19750042]

Burkhard, P.; Dominici, P.; Borri-Voltattorni, C.; Jansonius, J.N.; Malashkevich, V.N. Structural insight into Parkinson’s disease treatment from drug-inhibited DOPA decarboxylase. Nat. Struct. Biol., 2001, 8(11), 963-967.
[http://dx.doi.org/10.1038/nsb1101-963] [PMID: 11685243]

Montioli, R.; Voltattorni, C.B.; Bertoldi, M. Parkinson’s Disease: Recent Updates in the Identification of Human Dopa Decarboxylase Inhibitors. Curr. Drug Metab., 2016, 17(5), 513-518.
[http://dx.doi.org/10.2174/138920021705160324170558] [PMID: 27025882]

Parkinson Disease Agents. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury; National Institute of Diabetes and Digestive and Kidney Diseases: Bethesda, MD, 2012.

Fabbri, M.; Ferreira, J.J.; Rascol, O. COMT Inhibitors in the Management of Parkinson’s Disease. CNS Drugs, 2022, 36(3), 261-282.
[http://dx.doi.org/10.1007/s40263-021-00888-9] [PMID: 35217995]

Alonso, C.A.; Luquin, P.R.; García, Ruiz-Espiga, P.; Burguera, J.A.; Campos Arillo, V.; Castro, A.; Linazasoro, G.; López Del Val, J.; Vela, L.; Martínez Castrillo, J.C. Dopaminergic agonists in Parkinson’s disease. Neurologia, 2014, 29(4), 230-241.
[http://dx.doi.org/10.1016/j.nrl.2011.04.012] [PMID: 21724302]

Latt, M.D.; Lewis, S.; Zekry, O.; Fung, V.S.C. Factors to consider in the selection of dopamine agonists for older persons with Parkinson’s disease. Drugs Aging, 2019, 36(3), 189-202.
[http://dx.doi.org/10.1007/s40266-018-0629-0] [PMID: 30623310]

Tan, Y.Y.; Jenner, P.; Chen, S.D. Monoamine oxidase-B inhibitors for the treatment of Parkinson’s disease: Past, present, and future. J. Parkinsons Dis., 2022, 12(2), 477-493.
[http://dx.doi.org/10.3233/JPD-212976] [PMID: 34957948]

Nafisah, W.; Najman, A.H.; Hamizah, R.; Azmin, S.; Rabani, R.; Shah, S.; Norlinah, M. High prevalence of Helicobacter pylori infection in Malaysian Parkinson’s disease patients. Research and Reviews in Parkinsonism, 2013, 3, 63-67.

Pierantozzi, M.; Pietroiusti, A.; Galante, A.; Sancesario, G.; Lunardi, G.; Fedele, E.; Giacomini, P.; Stanzione, P. Helicobacter pylori-induced reduction of acute levodopa absorption in parkinson’s disease patients. Ann. Neurol., 2001, 50(5), 686-687.
[http://dx.doi.org/10.1002/ana.1267] [PMID: 11706979]

Rees, K.; Stowe, R.; Patel, S.; Ives, N.; Breen, K.; Clarke, C.E.; Ben-Shlomo, Y. Helicobacter pylori eradication for Parkinson’s disease. Cochrane Libr., 2011, (11), CD008453.
[http://dx.doi.org/10.1002/14651858.CD008453.pub2] [PMID: 22071847]

Pierantozzi, M.; Pietroiusti, A.; Brusa, L.; Galati, S.; Stefani, A.; Lunardi, G.; Fedele, E.; Sancesario, G.; Bernardi, G.; Bergamaschi, A.; Magrini, A.; Stanzione, P.; Galante, A. Helicobacter pylori eradication and l-dopa absorption in patients with PD and motor fluctuations. Neurology, 2006, 66(12), 1824-1829.
[http://dx.doi.org/10.1212/01.wnl.0000221672.01272.ba] [PMID: 16801644]

Bjarnason, I.T.; Charlett, A.; Dobbs, R.J.; Dobbs, S.M.; Ibrahim, M.A.A.; Kerwin, R.W.; Mahler, R.F.; Oxlade, N.L.; Peterson, D.W.; Plant, J.M.; Price, A.B.; Weller, C. Role of chronic infection and inflammation in the gastrointestinal tract in the etiology and pathogenesis of idiopathic parkinsonism. Part 2: response of facets of clinical idiopathic parkinsonism to Helicobacter pylori eradication. A randomized, double-blind, placebo-controlled efficacy study. Helicobacter, 2005, 10(4), 276-287.
[http://dx.doi.org/10.1111/j.1523-5378.2005.00330.x] [PMID: 16104943]

Beales, I.L.P.; Calam, J. Interleukin 1β and tumour necrosis factor α inhibit acid secretion in cultured rabbit parietal cells by multiple pathways. Gut, 1998, 42(2), 227-234.
[http://dx.doi.org/10.1136/gut.42.2.227] [PMID: 9536948]

El-Omar, E.M. The importance of interleukin 1β in Helicobacter pylori associated disease. Gut, 2001, 48(6), 743-747.
[http://dx.doi.org/10.1136/gut.48.6.743] [PMID: 11358884]

Takashima, M.; Furuta, T.; Hanai, H.; Sugimura, H.; Kaneko, E. Effects of Helicobacter pylori infection on gastric acid secretion and serum gastrin levels in Mongolian gerbils. Gut, 2001, 48(6), 765-773.
[http://dx.doi.org/10.1136/gut.48.6.765] [PMID: 11358893]

Feldman, M.; Cryer, B.; Lee, E. Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings. Am. J. Physiol. Gastrointest. Liver Physiol., 1998, 274(6), G1011-G1017.
[http://dx.doi.org/10.1152/ajpgi.1998.274.6.G1011] [PMID: 9696699]

Thor, P.; Lorens, K.; Tabor, S.; Herman, R.; Konturek, J.W.; Konturek, S.J. Dysfunction in gastric myoelectric and motor activity in Helicobacter pylori positive gastritis patients with non-ulcer dyspesia. J. Physiol. Pharmacol., 1996, 47(3), 469-476.
[PMID: 8877902]

Miyaji, H.; Azuma, T.; Ito, S.; Abe, Y.; Ono, H.; Suto, H.; Ito, Y.; Yamazaki, Y.; Kohli, Y.; Kuriyama, M. The effect of Helicobacter pylori eradication therapy on gastric antral myoelectrical activity and gastric emptying in patients with non-ulcer dyspepsia. Aliment. Pharmacol. Ther., 1999, 13(10), 1303-1309.
[http://dx.doi.org/10.1046/j.1365-2036.1999.00621.x] [PMID: 10540044]

Doherty, N.C.; Tobias, A.; Watson, S.; Atherton, J.C. The effect of the human gut-signalling hormone, norepinephrine, on the growth of the gastric pathogen Helicobacter pylori. Helicobacter, 2009, 14(3), 223-230.
[http://dx.doi.org/10.1111/j.1523-5378.2009.00682.x] [PMID: 19702852]

Yang, J.C.; Lu, C.W.; Lin, C.J. Treatment of Helicobacter pylori infection: Current status and future concepts. World J. Gastroenterol., 2014, 20(18), 5283-5293.
[http://dx.doi.org/10.3748/wjg.v20.i18.5283] [PMID: 24833858]

Gasbarrini, A.; Lauritano, E.C.; Gabrielli, M.; Scarpellini, E.; Lupascu, A.; Ojetti, V.; Gasbarrini, G. Small intestinal bacterial overgrowth: diagnosis and treatment. Dig. Dis., 2007, 25(3), 237-240.
[http://dx.doi.org/10.1159/000103892] [PMID: 17827947]

Gabrielli, M.; Bonazzi, P.; Scarpellini, E.; Bendia, E.; Lauritano, E.C.; Fasano, A.; Ceravolo, M.G.; Capecci, M.; Rita Bentivoglio, A.; Provinciali, L.; Tonali, P.A.; Gasbarrini, A. Prevalence of small intestinal bacterial overgrowth in Parkinson’s disease. Mov. Disord., 2011, 26(5), 889-892.
[http://dx.doi.org/10.1002/mds.23566] [PMID: 21520278]

Wanitschke, R.; Ammon, H.V. Effects of dihydroxy bile acids and hydroxy fatty acids on the absorption of oleic acid in the human jejunum. J. Clin. Invest., 1978, 61(1), 178-186.
[http://dx.doi.org/10.1172/JCI108916] [PMID: 338629]

Nucera, G.; Gabrielli, M.; Lupascu, A.; Lauritano, E.C.; Santoliquido, A.; Cremonini, F.; Cammarota, G.; Tondi, P.; Pola, P.; Gasbarrini, G.; Gasbarrini, A. Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth. Aliment. Pharmacol. Ther., 2005, 21(11), 1391-1395.
[http://dx.doi.org/10.1111/j.1365-2036.2005.02493.x] [PMID: 15932370]

Spencer, R.P. Intestinal absorption of amino acids. Current concepts. Am. J. Clin. Nutr., 1969, 22(3), 292-299.
[http://dx.doi.org/10.1093/ajcn/22.3.292] [PMID: 4237680]

Dobbs, R.J.; Charlett, A.; Dobbs, S.M.; Weller, C.; Peterson, D.W. Parkinsonism: differential age-trend in Helicobacter pylori antibody. Aliment. Pharmacol. Ther., 2000, 14(9), 1199-1205.
[http://dx.doi.org/10.1046/j.1365-2036.2000.00815.x] [PMID: 10971237]

Zimmermann, M.; Zimmermann-Kogadeeva, M.; Wegmann, R.; Goodman, A.L. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature, 2019, 570(7762), 462-467.
[http://dx.doi.org/10.1038/s41586-019-1291-3] [PMID: 31158845]

Gatto, M.; Fernandez Pardal, M.; Melero, M.; Zurru, C.; Scorticati, C.; Micheli, F. L-dopa malabsorption in a parkinsonian patient with Strongyloides stercoralis duodenitis. Clin. Neuropharmacol., 1994, 17(1), 96-98.
[http://dx.doi.org/10.1097/00002826-199402000-00012] [PMID: 8149365]

Pereira, C.I.; Matos, D.; San Romão, M.V.; Barreto Crespo, M.T. Dual role for the tyrosine decarboxylation pathway in Enterococcus faecium E17: response to an acid challenge and generation of a proton motive force. Appl. Environ. Microbiol., 2009, 75(2), 345-352.
[http://dx.doi.org/10.1128/AEM.01958-08] [PMID: 19011061]

Fallingborg, J. Intraluminal pH of the human gastrointestinal tract. Dan. Med. Bull., 1999, 46(3), 183-196.
[PMID: 10421978]