Neurogenic and anti-inflammatory effects of probiotics in Parkinson's disease: A systematic review of preclinical and clinical evidence

TY - JOUR

T1 - Neurogenic and anti-inflammatory effects of probiotics in Parkinson's disease

T2 - A systematic review of preclinical and clinical evidence

AU - Leta, Valentina

AU - Ray Chaudhuri, K.

AU - Milner, Oliver

AU - Chung-Faye, Guy

AU - Metta, Vinod

AU - Pariante, Carmine M.

AU - Borsini, Alessandra

N1 - Funding Information: VL has received grants from BRC, Parkinson’s UK, a travel and congress grant from Bial UK Ltd, speaker-related activities fees from Britannia pharmaceuticals, Bial UK, and consultancy fees from Invisio Pharmaceuticals, outside the submitted work. KRC has received honoraria for Advisory board from AbbVie, UCB, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile, Sunovion, Roche, Theravance, Scion, Britannia; honoraria for lectures from AbbVie, Britannia, UCB, Mundipharma, Zambon, Novartis, Boeringer Ingelheim; Grants (Investigator Initiated) from Britannia Pharmaceuticals, AbbVie, UCB, GKC, Bial; Academic grants from EU, IMI EU, Horizon 2020, Parkinson's UK, NIHR, PDNMG, EU (Horizon 2020), Kirby Laing Foundation, NPF, MRC, Wellcome Trust, outside the submitted work. OM has nothing to declare. AB and CMP are funded by the UK Medical Research Council (grants MR/L014815/1, MR/J002739/1 and MR/N029488/1), the European Commission Horizon 2020 (grant SC1-BHC-01-2019) and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London; they have also received research funding from Johnson & Johnson for research on depression and inflammation, but this paper is independent from this funding. In addition, CMP is funded by the Wellcome Trust strategy award to the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) Consortium (104025), which is also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer, but, again, this paper is independent from this funding. Funding Information: The authors acknowledge the support of the Movement Disorder Society Non-Motor PD Study Group, the National Institute for Health Research (NIHR) London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.Fig. 1 was created using Lucidchart.com. Fig. 2 was created using BioRender.com. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Funding Information: The authors acknowledge the support of the Movement Disorder Society Non-Motor PD Study Group, the National Institute for Health Research (NIHR) London South Clinical Research Network and the NIHR Biomedical Research Centre. This article represents independent collaborative research part-funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Fig. 1 was created using Lucidchart.com. Fig. 2 was created using BioRender.com. Publisher Copyright: © 2021 The Authors Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - There is increasing evidence highlighting the potential role of the gut-brain axis in the pathogenesis of Parkinson's disease (PD) and on the use of probiotics as a therapeutic strategy for this neurodegenerative disorder. While several studies have been published on the topic in recent years, there is still a lack of a comprehensive understanding of the effects of probiotics in PD and their possible underlying mechanisms. Through this systematic review, we collected a total of 17 articles, consisting of preclinical and clinical models of PD investigating the effect of probiotics on (1) energy metabolism, (2) inflammation and oxidative stress, (3) neurodegeneration, as well as (4) motor and (5) non-motor function. Articles were obtained from PubMed/Medline, Scopus, Web of Science and Embase databases. Findings from preclinical studies suggest that treatment with probiotics increases glucose metabolism (increased secretion of glucagon-like peptide-1), reduces peripheral and central inflammation (reduced interleukin-6 and tumor necrosis factor-α (TNF-α)), reduces peripheral and central oxidative stress (reduced peripheral superoxide anion levels and increased central antioxidant glutathione levels), decreases neurodegeneration (increased numbers of tyrosine hydroxylase dopaminergic neurons and levels of brain-derived neurotrophic factor), increases motor function (increased motor agility) and non-motor function (decreased memory deficits). Similarly, findings from clinical studies suggest that probiotics increase glucose metabolism (reduced insulin resistance), reduce peripheral inflammation (reduced peripheral TNF-α expression and C-reactive protein levels), and increase motor and non-motor function (decreased overall PD symptomatology and constipation); however, findings on oxidative stress were inconclusive across studies. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of probiotics on molecular and cellular mechanisms, as well as behavioural phenotypes, in either preclinical or clinical studies in PD. However, additional and more robust studies are still needed to confirm these outcomes, and should aim to focus more on bench-to-bedside approaches, in order to address the existing gaps between preclinical and clinical findings in this field.

AB - There is increasing evidence highlighting the potential role of the gut-brain axis in the pathogenesis of Parkinson's disease (PD) and on the use of probiotics as a therapeutic strategy for this neurodegenerative disorder. While several studies have been published on the topic in recent years, there is still a lack of a comprehensive understanding of the effects of probiotics in PD and their possible underlying mechanisms. Through this systematic review, we collected a total of 17 articles, consisting of preclinical and clinical models of PD investigating the effect of probiotics on (1) energy metabolism, (2) inflammation and oxidative stress, (3) neurodegeneration, as well as (4) motor and (5) non-motor function. Articles were obtained from PubMed/Medline, Scopus, Web of Science and Embase databases. Findings from preclinical studies suggest that treatment with probiotics increases glucose metabolism (increased secretion of glucagon-like peptide-1), reduces peripheral and central inflammation (reduced interleukin-6 and tumor necrosis factor-α (TNF-α)), reduces peripheral and central oxidative stress (reduced peripheral superoxide anion levels and increased central antioxidant glutathione levels), decreases neurodegeneration (increased numbers of tyrosine hydroxylase dopaminergic neurons and levels of brain-derived neurotrophic factor), increases motor function (increased motor agility) and non-motor function (decreased memory deficits). Similarly, findings from clinical studies suggest that probiotics increase glucose metabolism (reduced insulin resistance), reduce peripheral inflammation (reduced peripheral TNF-α expression and C-reactive protein levels), and increase motor and non-motor function (decreased overall PD symptomatology and constipation); however, findings on oxidative stress were inconclusive across studies. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of probiotics on molecular and cellular mechanisms, as well as behavioural phenotypes, in either preclinical or clinical studies in PD. However, additional and more robust studies are still needed to confirm these outcomes, and should aim to focus more on bench-to-bedside approaches, in order to address the existing gaps between preclinical and clinical findings in this field.

KW - Inflammation

KW - Metabolism

KW - Motor symptoms

KW - Neurodegeneration

KW - Non-motor symptoms

KW - Parkinson's disease

KW - Probiotics

UR - http://www.scopus.com/inward/record.url?scp=85112814077&partnerID=8YFLogxK

U2 - 10.1016/j.bbi.2021.07.026

DO - 10.1016/j.bbi.2021.07.026

M3 - Review article

AN - SCOPUS:85112814077

SN - 0889-1591

VL - 98

SP - 59

EP - 73

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

ER -