Risultati per: È confermato il legame tra la malattia di Alzheimer e microbiota intestinale

In Alzheimer disease (AD) research and care, novel biomarkers that measure amyloid-β (Aβ) and phosphorylated tau (P-tau)–the principal components of amyloid plaques and neurofibrillary tangles–have facilitated early detection and biomarker-supported diagnosis. Therapeutics that modify the biology of AD are being tested in clinical trials, leveraging biomarkers so that investigators select the right patients, evaluate target engagement, and gauge the effects of therapy on AD pathophysiology. The first class of therapies to reach the clinic in this modern era of AD drug development are Aβ-targeting monoclonal antibodies, which bind different species in the Aβ aggregation cascade. This treatment approach is grounded in the “amyloid hypothesis,” which postulates that Aβ aggregation triggers a cascade of pathophysiologic events, including synaptic and network dysfunction, neuroinflammation, and aggregation and spread of P-tau tangles. The spread of tangles is associated with synaptic loss and neurodegeneration, culminating in cognitive decline and dementia. By binding Aβ aggregates, monoclonal antibodies facilitate Aβ clearance from the brain, potentially mitigating both direct and downstream deleterious effects of Aβ and hence slowing cognitive decline.

Background
Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.

Objective
To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.

Design
An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.

Results and conclusions
Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.

Introduction
Aseptic abscess (AA) syndrome is a rare disease whose pathophysiology is unknown. It is often associated with inflammatory bowel disease and characterised by sterile inflammation with collections of neutrophils affecting several organs, especially the spleen. Microbiota are known to influence local and systemic immune responses, and both gut and oral microbiota perturbations have been reported in diseases associated with AA syndrome. However, interactions between these factors have never been studied in AA syndrome. The purpose of this translational case-control study (ABSCESSBIOT) is to investigate gut and/or oral microbiota in patients with AA syndrome compared with healthy controls. Moreover, microbiota associated metabolites quantification and Treg/Th17 balance characterisation will give a mechanistic insight on how microbiota may be involved in the pathophysiology of AA syndrome.

Methods and analysis
This French multicentre case-control study including 30 French centres (University hospital or regional hospital) aims to prospectively enrol 30 patients with AA syndrome with 30 matched controls and to analyse microbiota profiling (in stools and saliva), microbial metabolites quantification in stools and circulating CD4+ T cell populations.

Ethics and dissemination
This study protocol was reviewed and approved by an independent French regional review board (n° 2017-A03499-44, Comité de Protection des Personnes Ile de France 1) on 10 October 2022, and declared to the competent French authority (Agence Nationale de Sécurité du Médicament et des produits de santé, France). Oral and written informed consent will be obtained from each included patient and the control participant. Study results will be reported to the scientific community at conferences and in peer-reviewed scientific journals.

Trial registration number
Clinical Trials web-based platform (NCT05537909).

Gli operatori: “Reazione sorprendente” con la bambola iconica

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