Peripheral aetiopathogenic drivers and mediators of Parkinson’s disease and co-morbidities: role of gastrointestinal microbiota
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- 作者：Sylvia M. Dobbs ; R. John Dobbs ; Clive Weller ; André Charlett…
- 关键词：Aetiology ; Pathogenesis ; Parkinson’s and overlap diseases ; Helicobacter ; Intestinal dysbiosis ; Autoimmunity ; Bystander damage
- 刊名：Journal of NeuroVirology
- 出版年：2016
- 出版时间：February 2016
- 年：2016
- 卷：22
- 期：1
- 页码：22-32
- 全文大小：1,682 KB
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R. John Dobbs (1) (2) (3)
Clive Weller (1)
André Charlett (1) (4)
Aisha Augustin (1) (2)
David Taylor (1) (2)
Mohammad A. A. Ibrahim (5)
Ingvar Bjarnason (3)
1. Pharmaceutical Sciences, King’s College London, London, UK
2. The Maudsley Hospital, London, UK
3. Department of Gastroenterology, King’s College Hospital, London, UK
4. Statistics Unit, National Infection Service, Public Health England, London, UK
5. Diagnostic Immunology Laboratory, King’s College and St Thomas’s Hospitals, London, UK - 刊物主题：Neurosciences; Virology; Infectious Diseases; Immunology; Neurology;
- 出版者：Springer US
- ISSN：1538-2443
文摘
We seek an aetiopathogenic model for the spectrum of Parkinson’s disease (PD), functional bowel disease, depression and cognitive impairment. The adopted concept is that systemic immuno-inflammatory processes mediate neuro-inflammation. The model would be based on phenotype, exposome (including gastrointestinal microbiome), milieu (immuno-inflammatory and metabolome), human genetics and their interactions. It would enable a patient’s position, to be understood in terms of drivers, perpetuators and mediators, and a future position, with and without intervention, predicted. Even the cardinal facets of PD may have different drivers: halting one may allow escape down subordinate pathways. Peptic ulceration is prodromal to PD. In our randomised placebo-controlled trial, hypokinesia improved over the year following biopsy-proven Helicobacter pylori eradication and rigidity worsened. This was independent of any (stable, long t½) antiparkinsonian medication. There are pointers to an autoimmune process: for example, surveillance-confirmed hypokinesia effect was indication specific. During surveillance, successive antimicrobial courses, other than for Helicobacter, were associated with cumulative increase in rigidity. Exhibiting laxatives appeared to stem the overall temporal increase, despite antiparkinsonian medication, in rigidity. Thus, intestinal dysbiosis may be a major source of bystander neuronal damage. There are biological gradients of objective measures of PD facets on circulating inflammatory markers and leucocyte subset counts. Moreover, lactulose hydrogen breath test positivity for small-intestinal bacterial overgrowth (present in two thirds of PD patients) is associated with the same subsets: higher natural killer and total CD4+ counts and lower neutrophils. With greater aetiopathogenic understanding, relatively low cost and on-the-shelf medication could have a major impact. A new generation of animal models, based on the gut microbiome, is envisaged. Keywords Aetiology Pathogenesis Parkinson’s and overlap diseases Helicobacter Intestinal dysbiosis Autoimmunity Bystander damage