Gut bacterial tyrosine decarboxylases restrict the bioavailability of levodopa, the primary treatment in Parkinson’s disease

Abstract

22Human gut bacteria play a critical role in the regulation of immune and metabolic systems, as well as 23 in the function of the nervous system. The microbiota senses its environment and responds by 24 releasing metabolites, some of which are key regulators of human health and disease. In this study, we 25 identify and characterize gut-associated bacteria in their ability to decarboxylate L-3,4-26 dihydroxyphenylalanine (L-DOPA) via the tyrosine decarboxylases, which are mainly present in the 27 class Bacilli. Although the bacterial tyrosine decarboxylases have a higher affinity for tyrosine 28

Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome

“…It has recently become apparent that intestinal bacteria can regulate host serotonin metabolism [ [32] , [33] , [34] ], especially via the kynurenine pathway [ [35] , [36] , [37] ]. This pathway is also involved in the intestinal production of serotonin and dopamine and has been linked to central regulation of food intake in mice as well as intestinal passage time [ 38 ]. Another route of the gut-brain axis to modulate central control of food intake and metabolism may be via production of the short-chain fatty acid (SCFA) butyrate, which in humans is produced by intestinal bacteria from dietary fiber [ 39 ] and absorbed in the colon where it provides energy for colonic epithelial cells.…”

Potential binding modes of the gut bacterial metabolite, 5-hydroxyindole, to the intestinal L-type calcium channels and its impact on the microbiota in rats

“…We compiled a pool of 17 easy-accessible indole derivatives, based on both the availability of the compounds and the main pharmacophore characteristics of the 5-hydroxyindole, e.g. the -OH, -NH along with the substitution pattern, specifically 5-hydroxyindole, 1 4-hydroxyindole, 2 6-hydroxyindole, 3 7-hydroxyindole, 4 5-aminoindole 5 and 5-methoxyindole, 6 5-ethoxyindole, 7 5-hydroxyindole-3-acetic acid, 8 5-hydroxy-2-carboxylic acid, 9 5-hydroxyoxindole, 10 5,6-dihydroxyindole, 11 indole, 12 indole-3-acetic acid, 13 indole-2-carboxylic acid, 14 indole-3-carboxaldehyde, 15 (1 H -Indol-3-yl) methanamine 16 and 1-methylindole 17 ( Figure 3a ). In addition, several of those analogues (i.e., compounds 1, 8, 10, 12, 13 and 15) are common metabolites in humans.…”

“…The gut microbiota produces a wide range of small bioactive molecules derived from various substrates, including dietary precursors and medications. 1 , 2 Such microbial conversion represents a significant regulatory mechanism by which gut microbes can alter intestinal host physiology, including gastrointestinal motility. 3–6 Recently, we have identified 5-hydroxyindole, a product of gut microbial conversion of the dietary supplement and antidepressant 5-hydroxytryptophan, as a potent accelerator of the gastrointestinal motility via its activation of L-type voltage-gated calcium channels (LTCCs) located on the colonic smooth muscle cells.…”

Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels

“…Rats from the vehicle group were treated for the same period of 11 days, but 5-HI was not added to the sucrose solution. A total of 10% sucrose solvent was used only for in vivo experiment as described before [ 1 ]. A total of 30 mg/kg of 5-HI was chosen based on previous report [ 87 ].…”

“…The gastrointestinal (GI) tract is home to trillions of microbes. The gut microbiota produces a wide range of small bioactive molecules derived from various substrates, including dietary precursors and medications [ 1 , 2 ]. Such microbial conversion represents a significant regulatory mechanism by which gut microbes can alter intestinal host physiology, including gut motility [ 3 , 4 ].…”