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      Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson’s Disease

      review-article
      , *
      Journal of Parkinson's Disease
      IOS Press
      Microbiota composition, bacterial metabolites, immune modulators, Parkinson’s disease, levodopa, dopamine

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          Abstract

          Increasing evidence is supporting the hypothesis of α-synuclein pathology spreading from the gut to the brain although the exact etiology of Parkinson’s disease (PD) is unknown. Furthermore, it has been proposed that inflammation, via the gastrointestinal tract, potentially through infections, may contribute to α-synuclein pathogenesis, and thus to the risk of developing PD. Recently, many studies have shown that PD patients have an altered microbiota composition compared to healthy controls. Inflammation in the gut might drive microbiota alterations or vice versa. Many studies focused on the detection of biomarkers of the etiology, onset, or progression of PD however also report metabolites from bacterial origin. These metabolites might reflect the bacterial composition and as well play an important role in immune homeostasis, ultimately affecting the progression of PD. Besides the bacterial metabolites, pharmacological treatment of PD might play a crucial role during the progression and thus treatment of the disease on the immune system. This review aims to establish a link between the microbial composition with the observed alterations of bacterial metabolites and their impact on the immune system, which could have influential effect in onset, progression and etiology of PD.

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          Most cited references62

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          Hydrogen sulfide and cell signaling.

          Hydrogen sulfide (H₂S) is a gaseous mediator synthesized from cysteine by cystathionine γ lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H₂S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation. That H₂S inhibits cytochrome c oxidase and reduces cell energy production has been known for many decades, but more recently, a number of additional pharmacological targets for this gas have been identified. H₂S activates K(ATP) and transient receptor potential (TRP) channels but usually inhibits big conductance Ca²(+)-sensitive K(+) (BK(Ca)) channels, T-type calcium channels, and M-type calcium channels. H₂S may inhibit or activate NF-κB nuclear translocation while affecting the activity of numerous kinases including p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), and Akt. These disparate effects may be secondary to the well-known reducing activity of H₂S and/or its ability to promote sulfhydration of protein cysteine moieties within the cell.
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            Discovery and characterization of gut microbiota decarboxylases that can produce the neurotransmitter tryptamine.

            Several recent studies describe the influence of the gut microbiota on host brain and behavior. However, the mechanisms responsible for microbiota-nervous system interactions are largely unknown. Using a combination of genetics, biochemistry, and crystallography, we identify and characterize two phylogenetically distinct enzymes found in the human microbiome that decarboxylate tryptophan to form the β-arylamine neurotransmitter tryptamine. Although this enzymatic activity is exceedingly rare among bacteria more broadly, analysis of the Human Microbiome Project data demonstrate that at least 10% of the human population harbors at least one bacterium encoding a tryptophan decarboxylase in their gut community. Our results uncover a previously unrecognized enzymatic activity that can give rise to host-modulatory compounds and suggests a potential direct mechanism by which gut microbiota can influence host physiology, including behavior. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Links between diet, gut microbiota composition and gut metabolism.

              The gut microbiota and its metabolic products interact with the host in many different ways, influencing gut homoeostasis and health outcomes. The species composition of the gut microbiota has been shown to respond to dietary change, determined by competition for substrates and by tolerance of gut conditions. Meanwhile, the metabolic outputs of the microbiota, such as SCFA, are influenced both by the supply of dietary components and via diet-mediated changes in microbiota composition. There has been significant progress in identifying the phylogenetic distribution of pathways responsible for formation of particular metabolites among human colonic bacteria, based on combining cultural microbiology and sequence-based approaches. Formation of butyrate and propionate from hexose sugars, for example, can be ascribed to different bacterial groups, although propionate can be formed via alternative pathways from deoxy-sugars and from lactate by a few species. Lactate, which is produced by many gut bacteria in pure culture, can also be utilised by certain Firmicutes to form butyrate, and its consumption may be important for maintaining a stable community. Predicting the impact of diet upon such a complex and interactive system as the human gut microbiota not only requires more information on the component groups involved but, increasingly, the integration of such information through modelling approaches.
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                Author and article information

                Journal
                J Parkinsons Dis
                J Parkinsons Dis
                JPD
                Journal of Parkinson's Disease
                IOS Press (Nieuwe Hemweg 6B, 1013 BG Amsterdam, The Netherlands )
                1877-7171
                1877-718X
                09 October 2019
                30 October 2019
                2019
                : 9
                : Suppl 2 , Special Issue: The Gut-Brain Axis in Parkinson’s Disease Revisited
                : S359-S370
                Affiliations
                [1]Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen , Groningen, The Netherlands
                Author notes
                [* ]Correspondence to: Sahar El Aidy, Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute (GBB), University of Groningen, Nijenborgh 7, 9747 AG Groningen, The Netherlands. Tel.: +31 50 36 32201; Fax: +31 50 36 32154; E-mail: sahar.elaidy@ 123456rug.nl .
                Article
                JPD191780
                10.3233/JPD-191780
                6839483
                31609701
                ea0cb53b-a723-4a0f-8e41-4af128f5e6b0
                © 2019 – IOS Press and the authors. All rights reserved

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 18 September 2019
                Categories
                Review

                microbiota composition,bacterial metabolites,immune modulators,parkinson’s disease,levodopa,dopamine

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