Role of Helicobacters in Neuropsychiatric Disease: A Systematic Review in Idiopathic Parkinsonism

Abstract

<jats:p>Interest in an aetiopathogenic role for Helicobacter in neuropsychiatric diseases started with idiopathic parkinsonism (IP), where the cardinal signs can be assessed objectively. This systematic review, using an EMBASE database search, addresses Oxford Centre for Evidence-Based Medicine based questions on the inter-relationship of Helicobacter and IP, the benefits of eradicating Helicobacter in IP and the outcome of not treating. The search strategy was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines: 21 of 204 articles met the inclusion criteria. The results show that the assumption that any benefit of Helicobacter eradication results from improved levodopa bioavailability is unjustified. The inter-relationship between Helicobacter and IP is well-established. H. pylori virulence markers (associated with autoimmunity and immune tolerance) influence the risk, severity and progression of IP. The birth cohort effect for virulence marker antibodies, seen in controls, is obliterated in IP, suggesting causality. Successful H. pylori eradication in IP is disease-modifying (even in anti-parkinsonian treatment-naïve patients) but not preventive. Hypokinesia regresses with eradication and overall motor severity lessens. Eradication may influence gastrointestinal microbiota adversely, unlocking the next stage in the natural history, the development of rigidity. Failed eradication worsens hypokinesia, as does the presence/persistence of H. pylori at molecular level only. Adequate prognostic assessment of the consequences of not treating Helicobacter, for IP, is prevented by a short follow-up. We conclude that Helicobacter is a pathophysiological driver of IP.</jats:p>

The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders—An Evidence Mapping Based on Quantified Evidence

“…According to the AMSTAR-2 criteria, 21 SRs [7,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] scored "critically low," 16 SR [13,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] scored "low," and 5 SR [36,[52][53][54][55] scored "moderate" (Figure 2). The most frequent drawbacks were as follows: no mentioning of the protocol in the systematic overview, no description of the rationale for the study designs included in the review, and no statement of funding for the included studies.…”

Influence of probiotic bacteria on gut microbiota composition and gut wall function in an in-vitro model in patients with Parkinson's disease

“…Because PD patients often have a degree of gut inflammation, faecal calprotectin is frequently raised ( Weis et al, 2019 ) and has been suggested as an early biomarker for PD risk ( Mulak et al, 2019 ). The GI abnormalities (particularly permeability issues and the finding of intestinal inflammation) found in PD are common to many other diseases, but their importance is that these changes may reflect pathophysiological processes that aggravate certain symptoms of PD ( Tucker et al, 2020a , Tucker et al, 2020b ).…”

Infectious Agents as Potential Drivers of α‐Synucleinopathies

“…95 In addition, several reviews have specifically focused on the potential role of the bacterium Helicobacter pylori. 90,[99][100][101][102] The most recent meta-analysis 90 highlighted an increased risk of PD in subjects infected with this bacterium (pooled OR = 1.65 95% CI, 1.43-1.92, 9 studies published before 2019). Nevertheless, the benefit of its eradication on parkinsonian symptoms remains uncertain, 100 in particular in view of a recent randomized clinical trial showing no significant improvement in clinical outcomes at 12 and 52 weeks post-treatment.…”

“…A significant number of literature reviews have recently been published regarding the link between certain pathogens and the onset of PD 89‐110 . Consequently, the objective here is not to provide an exhaustive description of the currently existing results, but to provide a brief summary of the pathogens investigated while presenting the most recent and relevant reviews.…”

“…The second (11 studies published before February 2021, 692 patients with PD and 281 controls) showed a higher prevalence of small intestinal bacterial overgrowth, as measured using either lactulose or glucose hydrogen breath tests, in patients with PD than in controls (pooled odds ratio [OR] = 5.22 95% confidence interval [CI], 3.33–8.19) 95 . In addition, several reviews have specifically focused on the potential role of the bacterium Helicobacter pylori 90,99‐102 . The most recent meta‐analysis 90 highlighted an increased risk of PD in subjects infected with this bacterium (pooled OR = 1.65 95% CI, 1.43–1.92, 9 studies published before 2019).…”