NapBiome trial: Targeting gut microbiota to improve sleep rhythm and developmental and behavioural outcomes in early childhood in a birth cohort in Switzerland – a study protocol

Introduction
The gut–brain axis plays a crucial role in the regulation and development of psychological and physical processes. The first year of life is a critical period for the development of the gut microbiome, which parallels important milestones in establishing sleep rhythm and brain development. Growing evidence suggests that the gut microbiome influences sleep, cognition and early neurodevelopment. For term-born and preterm-born infants, difficulties in sleep regulation may have consequences on health. Identifying effective interventions on the gut–brain axis in early life is likely to have long-term implications for the health and development of at-risk infants.

Methods and analyses
In this multicentre, four-group, double-blinded, placebo (PLC)-controlled randomised trial with a factorial design, 120 preterm-born and 260 term-born infants will be included. The study will investigate whether the administration of daily synbiotics or PLC for a duration of 3 months improves sleep patterns and neurodevelopmental outcomes up to 2 years of age. The trial will also: (1) determine the association between gut microbiota, sleep patterns and health outcomes in children up to 2 years of age; and (2) leverage the interactions between gut microbiota, brain and sleep to develop new intervention strategies for at-risk infants.

Ethics and dissemination
The NapBiome trial has received ethical approval by the Committee of Northwestern and Central Switzerland and Canton Vaud, Switzerland (#2024–01681). Outcomes will be disseminated through publication and will be presented at scientific conferences. Metagenomic data will be shared through the European Nucleotide Archive.

Trial registration number
The US National Institutes of Health NCT06396689.

Leggi
Marzo 2025

Blood Biomarkers to Detect Alzheimer Disease

To the Editor In their excellent research, Dr Palmqvist and colleagues report high diagnostic accuracy of blood biomarkers in the diagnosis of Alzheimer disease. The authors used the STROBE checklist for observational studies, but this is a prospective diagnostic accuracy study, for which the STARD checklist is more appropriate.

Leggi
Febbraio 2025

Cirrhosis and Faecal microbiota Transplantation (ChiFT) protocol: a Danish multicentre, randomised, placebo-controlled trial in patients with decompensated liver cirrhosis

Introduction
Liver cirrhosis is a progressive disease with high mortality. Gut microbiota derangement, increased gut permeability, bacterial translocation and chronic inflammation all drive disease progression. This trial aims to investigate whether faecal microbiota transplantation (FMT) may improve the disease course in patients with acute decompensation of liver cirrhosis.

Methods and analysis
In this Danish, multicentre, randomised, double-blinded, placebo-controlled trial, 220 patients with acute decompensation of liver cirrhosis and a Child-Pugh score≤12 will be randomised (1:1) to oral, encapsulated FMT or placebo in addition to standard of care. Before the intervention, the patients will be examined and biological samples obtained, and this is repeated at 1 and 4 weeks and 3, 6 and 12 months after the intervention. The primary outcome is the time from randomisation to new decompensation or death. Secondary endpoints include mortality, number of decompensation events during follow-up and changes in disease severity and liver function.

Ethics and dissemination
The Central Denmark Region Research Ethics Committee approved the trial protocol (no. 1-10-72-302-20). The results will be published in an international peer-reviewed journal, and all patients will receive a summary of the results.

Trial registration number
ClinicalTrials.gov study identifier NCT04932577.

Leggi
Febbraio 2025

Human Papillomavirus, Human Immunodeficiency Virus, and Oral Microbiota Interplay in Nigerian Youth (HOMINY): A Prospective Cohort Study Protocol

Introduction
Persistent oral infections with high-risk human papillomavirus (HR-HPV) are a potential cause of most oropharyngeal cancers (OPCs). Oral HR-HPV infection and persistence are significantly higher in people living with HIV (PLWH). Most data on oral HR-HPV in PLWH come from developed countries or adult cohorts. This study aims to investigate oral HR-HPV susceptibility and persistence among children and adolescents living with HIV (CALHIV) and to understand the roles of perinatal HIV exposure, infection, antiretroviral treatment, and the oral microbiome.

Methods and analysis
This prospective cohort study is ongoing at the University of Benin Teaching Hospital (UBTH), Nigeria, involving mother-child pairs followed at 6-month intervals for 2 years. Participants include children aged 9–18 and their mothers aged 18 and above. The study targets 690 adolescents in three groups: 230 CALHIV, 230 HIV-exposed but uninfected and 230 HIV-unexposed and uninfected. Oral rinse, saliva, buccal swabs and supragingival plaque samples are collected at each visit. Blood samples are tested for HIV, Hepatitis B virus (HBV) and Hepatitis C virus (HCV), with CD4, CD8 and full blood counts performed. Oral HPV is assessed for incidence, persistence, and clearance. Statistical analyses to look for associations between cohort baseline characteristics and findings will be conducted using univariable and multivariable models for repeated data and high-dimensional microbiome data. All statistical tests will be two-sided; a p value

Leggi
Febbraio 2025

Abstract TP393: Reducing Neutrophil Sialic Acid Residues Alleviates Cerebral Hypoperfusion in Alzheimer’s Models

Stroke, Volume 56, Issue Suppl_1, Page ATP393-ATP393, February 1, 2025. Dysregulation of the immune system is a contributing factor in the progression of Alzheimer’s Disease (AD), likely by increased vascular inflammation triggered by brain or peripheral inflammation. Our research has demonstrated that neutrophils play a role in causing hypoperfusion by adhering to and obstructing blood vessels, as seen in both mouse models for and patients with AD. Notably, protein glycosylation of membrane proteins is essential for regulating the adhesion properties of neutrophils to immune cells and the vasculature.Here, we utilize lectin blots to show that sialic acid residues, which are the terminal caps of glycosylation chains, are increased on neutrophil membrane proteins from an amyloidosis Alzheimer’s mouse model. Furthermore, we evaluated the efficacy of the sialyltransferase inhibitor alpha 2,3 sialyltransferase-IN-1 by lectin blot analyses, identifying it to be an effective compound for removing sialic acid from neutrophil membrane proteins. Notably, we performedin vivomultiphoton imaging of cerebral blood flow and capillary stalling in AD mice injected with alpha 2,3 sialyltransferase-IN-1. Our findings demonstrated that reducing sialic acid residues on neutrophils improved cerebral blood flow and capillary stalling.This work suggests that the altered glycosylation pattern, specifically aberrant sialylation residues of neutrophil glycoproteins, are a significant contributing factor to the hypoperfusion observed in AD mouse models and patients. Modulating the glycosylation profile may present a potential therapeutic approach for improving the vascular dysfunction associated with AD pathogenesis.

Leggi
Gennaio 2025