Search Results for: È confermato il legame tra la malattia di Alzheimer e microbiota intestinale

This Viewpoint discusses how data gaps in published research impede clinicians’ ability to clearly discuss the risks and benefits of amyloid-lowering drugs for treating Alzheimer disease.

Introduction
A better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an elevated risk of AD and related dementias based on health registry information. Here, we establish the protocol for an observational clinical recall and biomarker study called TWINGEN with the aim to identify individuals at high risk of AD by assessing cognition, health and AD-related biomarkers. Suitable candidates were identified and invited to participate in the new study among THL Biobank donors according to TWINGEN study criteria.

Methods and analysis
A multi-centre study (n=800) to obtain blood-based biomarkers, telephone-administered and web-based memory and cognitive parameters, questionnaire information on lifestyle, health and psychological factors, and accelerometer data for measures of physical activity, sedentary behaviour and sleep. A subcohort is being asked to participate in an in-person neuropsychological assessment (n=200) and wear an Oura ring (n=50). All participants in the TWINGEN study have genome-wide genotyping data and up to 48 years of follow-up data from the population-based older Finnish Twin Cohort (FTC) study of the University of Helsinki. The data collected in TWINGEN will be returned to THL Biobank from where it can later be requested for other biobank studies such as FinnGen that supported TWINGEN.

Ethics and dissemination
This recall study consists of FTC/THL Biobank/FinnGen participants whose data were acquired in accordance with the Finnish Biobank Act. The recruitment protocols followed the biobank protocols approved by Finnish Medicines Agency. The TWINGEN study plan was approved by the Ethics Committee of Hospital District of Helsinki and Uusimaa (number 16831/2022). THL Biobank approved the research plan with the permission no: THLBB2022_83.

Gastrointestinal biofilms are highly heterogenic and spatially organised polymicrobial communities that can expand and cover large areas in the gastrointestinal tract. Gut microbiota dysbiosis, mucus disruption, and epithelial invasion are associated with pathogenic biofilms that have been linked to gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), gastric cancer, and colon cancer. Intestinal biofilms are highly prevalent in ulcerative colitis and IBS patients, and most endoscopists will have observed such biofilms during colonoscopy, maybe without appreciating their biological and clinical importance.

I consulenti dell’Fda hanno approvato il farmaco di Eli Lilly. Entro la fine dell’anno si attende l’ok definitivo da parte dell’Ente regolatorio

Introduction
The observed alteration of the intestinal microbiota in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the effect of transferring a healthy gut flora from a faecal donor using a faecal microbiota transplantation (FMT) will be explored in this trial.

Methods and analysis
This is a protocol for a randomised, double-blind, placebo-controlled, parallel-group, single-centre trial, with 12 months follow-up. 80 participants will be included and randomised (1:1:2) to either donor FMT (from two different donors) or placebo (autologous FMT). Participants will be included by the International Clinical Criteria for ME/CFS. The clinical measures of ME/CFS and disease activity include Modified DePaul Questionnaire, Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), 36-Item Short Form Health Survey (SF-36), ROMA IV criteria, Food Frequency Questionnaire, Repeatable Battery for the Assessment of Neuropsychological Status, heart rate variability testing and reports on the use of antibiotics and food supplements, as well as biobanking of blood, urine and faeces.
The primary endpoint is proportion with treatment success in FSS score in donor versus autologous FMT group 3 months after treatment. Treatment success is defined as an FSS improvement of more than 1.2 points from baseline at 3 months after treatment. Adverse events will be registered throughout the study.

Ethics and dissemination
The Regional Committee for Medical Research Ethics Northern Norway has approved the study. The study has commenced in May 2019. Findings will be disseminated in international peer-reviewed journal(s), submitted to relevant conferences, and trial participants will be informed via phone calls.

Trial registration number
NCT03691987.

Circulation, Ahead of Print. BACKGROUND:A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-β peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction).METHODS:In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0–30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSEs score of ≥3 points), cognitive impairment (MMSE score

The current European guidelines (Maastricht VI/Florence consensus report) on the management of Helicobacter pylori infection1 recommend population-based H. pylori screening programmes for asymptomatic individuals in the general population to eradicate the microorganism for gastric cancer prevention. However, this is expected to result in a considerable increase in antibiotic use2 as half of the global population are estimated to be infected.3 Therefore, the guidelines suggest that caution is required in choosing the appropriate antibiotics to minimise antimicrobial resistance.1 The importance of gut resistome induction following H. pylori eradication therapies has been debated for years, and the available information is controversial; the general thought is that normal gut microbiota is restored 3–6 months after antibiotic treatment.4 Therefore, we conducted a randomised controlled clinical trial as part of the GISTAR study5 in Latvia by evaluating alterations in gut microbiota before…

We read with interest the recent report by Nashed et al that described changes in the microbiota caused by viral infections, which in turn affected the severity of the clinical disease.1–4 Interactions between viral infections and microbiota complicate their relationship with host immunity and clinical diseases. However, it is unclear whether those associations are causal. Furthermore, the interactions between the microbiota and infections, as well as the outcomes of those interactions, have only been studied to a limited extent.5–8 We conducted an in-depth statistical analysis based on two-sample bidirectional Mendelian randomisation (MR) to broaden our understanding and provide a comprehensive assessment of the causal relationship between 9 common infections, 140 microbes and 38 clinical diseases. As instrumental variables for MR analysis, independent genetic variants with genome-wide suggestive significance (p

Postprandial, or meal-related, symptoms, such as abdominal pain, early satiation, fullness or bloating, are often reported by patients with disorders of gut-brain interaction, including functional dyspepsia (FD) or irritable bowel syndrome (IBS). We propose that postprandial symptoms arise via a distinct pathophysiological process. A physiological or psychological insult, for example, acute enteric infection, leads to loss of tolerance to a previously tolerated oral food antigen. This enables interaction of both the microbiota and the food antigen itself with the immune system, causing a localised immunological response, with activation of eosinophils and mast cells, and release of inflammatory mediators, including histamine and cytokines. These have more widespread systemic effects, including triggering nociceptive nerves and altering mood. Dietary interventions, including a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols, elimination of potential food antigens or gluten, IgG food sensitivity diets or salicylate restriction may benefit some patients with IBS or FD. This could be because the restriction of these foods or dietary components modulates this pathophysiological process. Similarly, drugs including proton pump inhibitors, histamine-receptor antagonists, mast cell stabilisers or even tricyclic or tetracyclic antidepressants, which have anti-histaminergic actions, all of which are potential treatments for FD and IBS, act on one or more of these mechanisms. It seems unlikely that food antigens driving intestinal immune activation are the entire explanation for postprandial symptoms in FD and IBS. In others, fermentation of intestinal carbohydrates, with gas release altering reflex responses, adverse reactions to food chemicals, central mechanisms or nocebo effects may dominate. However, if the concept that postprandial symptoms arise from food antigens driving an immune response in the gastrointestinal tract in a subset of patients is correct, it is paradigm-shifting, because if the choice of treatment were based on one or more of these therapeutic targets, patient outcomes may be improved.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Background
The mechanism by which proton pump inhibitors (PPIs) alter gut microbiota remains to be elucidated. We aimed to learn whether PPI induced gut microbiota alterations by promoting oral microbial translocation.

Methods
Healthy adult volunteers were randomly assigned: PP group (n=8, 40 mg esomeprazole daily for seven days) and PM group (n=8, 40 mg esomeprazole along with chlorhexidine mouthwash after each meal for seven days). Fecal and saliva samples were analysed using 16S ribosomal RNA sequencing. Mouse models were introduced to confirm the findings in vivo, while the effect of pH on oral bacteria proliferation activity was investigated in vitro.

Results
Taxon-based analysis indicated that PPI administration increased Streptococcus abundance in gut microbiota (P

Objective
We aim to compare the effects of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) on the gut microbiota through longitudinal analysis.

Design
Healthy volunteers were randomly assigned to receive either PPI (n=23) or H2RA (n=26) daily for seven consecutive days. We collected oral (saliva) and faecal samples before and after the intervention for metagenomic next-generation sequencing. We analysed intervention-induced alterations in the oral and gut microbiome including microbial abundance and growth rates, oral-to-gut transmissions, and compared differences between the PPI and H2RA groups.

Results
Both interventions disrupted the gut microbiota, with PPIs demonstrating more pronounced effects. PPI usage led to a significantly higher extent of oral-to-gut transmission and promoted the growth of specific oral microbes in the gut. This led to a significant increase in both the number and total abundance of oral species present in the gut, including the identification of known disease-associated species like Fusobacterium nucleatum and Streptococcus anginosus. Overall, gut microbiome-based machine learning classifiers could accurately distinguish PPI from non-PPI users, achieving an area under the receiver operating characteristic curve (AUROC) of 0.924, in contrast to an AUROC of 0.509 for H2RA versus non-H2RA users.

Conclusion
Our study provides evidence that PPIs have a greater impact on the gut microbiome and oral-to-gut transmission than H2RAs, shedding light on the mechanism underlying the higher risk of certain diseases associated with prolonged PPI use.

Trial registration number
ChiCTR2300072310.

As reviewed by us recently,1 an increasing number of studies suggest that the gut microbiota is an important regulator of immune responses to vaccination. Consistent with these data, several recent clinical studies,2–4 including three published in Gut,5–7 uncover correlations between the composition of the faecal/gut microbiota and antibody responses to different COVID-19 vaccines. Additionally, recent antibiotic usage has also been associated with a lower seroconversion rate following BNT162b2 vaccination.8 These studies suggest that the gut microbiota plays a significant role in regulating optimal immune responses to COVID-19 vaccines. Despite these important studies, the causal and mechanistic links between the gut microbiota and responses to COVID-19 vaccines remain to be elucidated. To investigate these links, we turned to two well-established models used previously to assess the relationship between the gut microbiota and responses to…

L’Italia beneficerebbe di maggiori export verso i Paesi africani più colpiti dalla malattia per oltre 280 milioni di dollari entro il 2030

La malattia trasmessa dalle zanzare comincia a diffondersi anche a queste latitudini a causa dei cambiamenti climatici