Risultati per: GUT

Introduction
During the pandemic, overweight and obese adolescents were at a higher risk of COVID-19 infection. Indonesia’s government has implemented prevention programmes and immunisation; however, the rise in SARS-CoV-2 infections among adolescents is exacerbated by low-quality diet and lifestyle habits. Also, the vaccine programme is not prioritised in this population. To address this, a solution involves providing probiotics and counselling on healthy lifestyle habits to improve diet and immunity. Therefore, we designed a protocol for a randomised controlled trial with a 20-week intervention to investigate the effect of probiotics supplementation and counselling on healthy lifestyle habits, including healthy eating and physical activity, and psychosocial stimulation, on nutritional status and antibody response against SARS-CoV-2 in this group.

Methods and analysis
This clinical trial aims to investigate the effects of probiotic supplementation on healthy overweight and obese adolescents. The study will involve 440 adolescents aged 12–17 living in Jakarta, Surabaya or Yogyakarta for at least 6 months and have completed at least two doses of the COVID-19 vaccine. The intervention group will receive daily probiotic supplementation of three strains, including Bifidobacterium animalis subsp. Lactis (BB-12), Lactobacillus acidophilus (LA-5) and Lactobacillus rhamnosus (LGG), at the level of 109–1010 colony-forming units for 20 weeks, while the control group will receive a placebo. Both groups will receive weekly counselling on healthy eating habits, physical activity and psychosocial stimulation. The primary outcomes will be changes in the body mass index for age z-score and IgG specific to SARS-CoV-2 titre concentrations between groups. The secondary outcomes will include changes in secretory IgA specific to SARS-CoV-2 titre concentrations, monoclonal antibodies against SARS-CoV-2 spike protein, gut microbiota diversity and the score of Healthy Eating Index 2015.

Ethics and dissemination
The study protocol was approved by the Ethics Committee of the Faculty of Medicine, Universitas Indonesia-Cipto Mangunkusumo Hospital (KET 763/UN2.F1/ETIK/PPM.00.02/2022: 1 August 2022). The study results will be disseminated in open-access international journals, scientific meetings and conferences with stakeholders.

Trial registration number
The study has been registered at https://clinicaltrials.gov with identifier number NCT05623007.

The gut microbiome is involved in human health and disease, and its comprehensive understanding is necessary to exploit it as a diagnostic or therapeutic tool. Multi-omics approaches, including metagenomics, metatranscriptomics, metabolomics, and metaproteomics, enable depicting the complexity of the gut microbial ecosystem. However, these tools generate a large data stream, which integration is needed to produce clinically useful readouts but, in turn, might be difficult to carry out with conventional statistical methods.

Introduction
Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis, is characterised by chronic and relapsing inflammation of the gastrointestinal tract, leading to significant morbidity and reduced quality of life. The global rise in IBD incidence is driven by a complex interplay of genetic, environmental, dietary and microbiome-related factors. Despite advancements in treatment, such as biologics, response rates remain variable, highlighting the need for personalised approaches. Recent research suggests that specific microbiome signatures may serve as biomarkers for predicting therapeutic efficacy, offering a potential tool for optimising treatment strategies in CD. The aim of the Optimising IBD Patient Treatment with Integrated Microbiome Investigation for Specialised Therapeutics (OPTIMIST) study is to evaluate microbiome profiles across various sample types in a Canadian CD cohort starting or already on advanced therapy, with the goal of developing predictive models for personalised therapeutics.

Methods and analysis
This study is a two-phase, longitudinal, prospective observational pilot study conducted in British Columbia, Canada, involving both CD patients and non-IBD controls. Phase 1 focuses on baseline microbiome differences across participant cohorts through cross-sectional analysis. Phase 2 follows participants over 12 months to assess microbiome changes and their association with treatment response. Stool samples, intestinal biopsies from the left colon, right colon and ileum, as well as mucosal wash samples from the proximal part of the distal colon, will undergo metagenomics, metaproteomics and metabolomics analyses to explore compositional and functional differences. Data will be analysed using alpha and beta diversity metrics, differential abundance analyses and multivariate analyses to identify microbiome-based predictors of therapeutic response.

Ethics and dissemination
Ethical approval was received by the Research Ethics Board (REB) of University of British Columbia-Providence Healthcare (UBC-PHC) with a REB number H23-02927. All amendments to the protocol are reported and adapted based on the requirements of the REB. The results of this study will be submitted to peer-reviewed journals and will be communicated in editorials/articles by the IBD Centre of BC and BC Children’s Hospital Research Institute.

Trial registration number
NCT06453720.

Protocol version
2024-06-21, version 3.0.

We have read with interest the article by Bonfils et al, which explores the impact of parental IBD on offspring risk using a large Danish cohort.1 Their findings underscore the significance of genetic predisposition and shared environmental factors, with maternal IBD diagnosis before childbirth showing the highest risk (adjusted HR 6.27) and a similar pattern observed with paternal IBD (adjusted HR 5.26). Despite the clear inheritance pattern indicated by Bonfils et al, previous genome-wide association studies (GWAS) have shown that genetic predisposition accounts for only a small portion of IBD risk, ranging from 8.2% to 13.1%.2 This suggests that a substantial portion of IBD risk remains unexplained by genetics alone. Traditional GWAS approaches typically focus on direct associations between single nucleotide polymorphisms (SNPs) and disease phenotypes, overlooking complex biological interactions among genes, gut microbiota and blood metabolites that shape IBD.3 Furthermore, the extent…

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.

Objectives
To compare costs, health outcomes and cost-effectiveness of using intravenous lidocaine (bolus given at induction of anaesthesia, followed by infusion for 6–12 hours) during colorectal surgery to improve the return of gastrointestinal function.

Design
Within-trial planned analysis of data from a randomised controlled trial using an intention-to-treat approach.

Setting
27 hospitals from across the UK.

Participants
557 patients aged 25–91 having minimally invasive elective colorectal resection.

Intervention
A 1:1 randomisation between intravenous lidocaine and placebo, minimised for age (

We recently showed that a bacterial infection can break oral tolerance to food and lead to IgE-dependent mast cell activation and food-induced abdominal pain, which could constitute an important pathogenic mechanism in post-infectious irritable bowel syndrome (IBS). Here, we investigated whether similar immune mechanisms in response to psychological stress lead to food-evoked pain signaling, and thus potentially explain the pathophysiology in a larger group of patients with IBS.

The benefits of regular physical activity (PA) on disease prevention and treatment outcomes have been recognized for centuries. However, only recently has interorgan communication triggered by the release of “myokines” from contracting skeletal muscles emerged as a putative mechanism by which exercise confers protection against numerous disease states. Cross-talk between active skeletal muscles and the gut microbiota reveal how regular PA boosts host immunity, facilitates a more diverse gut microbiome and functional metabolome, and plays a positive role in energy homeostasis and metabolic regulation.

Advances in understanding the pathogenesis of inflammatory bowel disease (IBD) point toward a key role of the gut microbiome. We review the data describing the changes in the gut microbiome from IBD case-control studies and compare these findings with emerging data from studies of the preclinical phase of IBD. What is apparent is that assessing changes in the composition and function of the gut microbiome during the preclinical phase helps address confounding factors, such as disease activity and drug therapy, which can directly influence the gut microbiome.

Stroke, Volume 56, Issue Suppl_1, Page ATP337-ATP337, February 1, 2025. Background and Purpose:Our previous studies in a rat model of ischemic stroke identified that intraperitoneal (IP), but not intracerebroventricular (ICV) administration of IGF-1 reduced stroke-induced gut leakiness and peripheral inflammation in the acute phase and attenuated stroke-induced impairment in acyclic middle-aged female rats. These data suggest that the gut may be implicated in IGF-1-mediated effects on stroke-induced cognitive impairment. To directly assess whether the effect of IGF-1 on behavioral improvement is mediated by the gut, study utilized a novel tet-inducible rAAV construct to block IGF1R specifically in the gut.Methods:Female Sprague Dawley rats (9-11 mo) were intragastrically gavaged with either recombinant rAAV construct containing IGFR-shRNA (IGFR-sh) downstream of the IESC promoter Lgr5 in a Tet-inducible system or rAAV-empty vector (Scr-sh) 4 weeks prior to experimental ischemia. Animals were subjected to endothelin-1 induced MCAo. Doxycycline was administered 4h later and IGF-1 was given ip at 4 and 24 h post-stroke. Sensorimotor function as well as peripheral inflammation (in serum samples) was assessed at 5d post-stroke and long-term cognitive impairment was evaluated after 60 days.Results:The mCherry reporter in the rAAV construct was observed in the intestinal crypt, indicating appropriate delivery of the construct. Sensorimotor function evaluated by vibrissae evoked forelimb placement task was significantly impaired in the ipsilateral paw after stroke in IGFR-Sh+IGF-1 compared to Scr-sh+IGF-1(p

Stroke, Volume 56, Issue Suppl_1, Page ATMP116-ATMP116, February 1, 2025. Background and Purpose:Gut microbiota dysfunction is associated with diabetic cognitive impairment (DCI). However, the mechanisms underlying the interaction of gut microbiota dysbiosis and DCI remain poorly understood. We tested the hypothesis that extracellular vesicles generated by diabetic gut microbiota exacerbate DCI by promoting the impairment of cerebral vascular function.Methods:Gut-EVs from the stools of male non-diabetic dm (dm-gut-EVs) and diabetic (db/db mice) with DCI (db-gut-EVs) mice at 20 weeks of age (20W) were isolated and characterized by means of ultracentrifugation and 16S rRNA sequencing, respectively. Given that db/db mice develop cognitive deficits at 20W, prediabetic db/db mice at 8 weeks of age (8W) were treated with gut-EVs at a dose of 1x1010particles/injection intravenously twice a week for 12 weeks. Cognitive performance was assessed using a battery of behavioral tests.Results:16S rRNA analysis revealed significant alterations in the microbiota composition of db-gut-EVs derived from 20W db/db mice with DCI compared to dm-gut-EVs (n=5/group). Db/db mice treated with db-gut-EVs extracted at 20W, but not with dm-gut-EVs, exhibited a significant decline in learning and memory function, as assayed by the Novel object recognition, Social recognition memory, and Morris water maze assay, starting at 16W and worsening at 20W, compared to db/db mice treated with saline (n=10/group). Additionally, db/db mice treated with db-gut-EVs exhibited increased cerebral vascular thrombosis (18±2 vs 11±2 Fibrin+ vessels/mm2in saline, p

Stroke, Volume 56, Issue Suppl_1, Page ATP38-ATP38, February 1, 2025. Introduction:The gut-brain axis is pivotal in recovery after stroke, with the gut microbiome playing a significant role in neurological outcomes.Akkermansia muciniphila(AKK), a beneficial gut bacterium, has shown promise in metabolic conditions. We hypothesize that AKK and its exosomes (AKK-Exo) can enhance stroke recovery by modulating gut-brain interactions.Methods: Human study:fecal samples from 88 ischemic stroke (IS) patients and 23 healthy elderly were analyzed using 16S rDNA sequencing. Animal study: 6-8 months old male mice subjected to photothrombotic middle cerebral artery occlusion were treated intragastrically with either AKK or AKK-Exo. Neurological recovery was evaluated over 2 weeks, accompanied by 16S rDNA sequencing and metabolomics analysis of fecal and plasma samples. The RT-PCR, Western blotting, and immunofluorescence were employed to assess inflammation, microglial activation, and white matter (WM) remodeling in the brain.Results:Human study demonstrated that IS disrupts gut microbiota, with an increase in pathogenic bacteria likeParabacteroidesand a decrease in beneficial microbes likeLachnospira. Patients with higher levels of AKK exhibited better neurological outcomes. In the mouse model, both AKK and AKK-Exo treatments resulted in improvements in neurological function, also led to a restructuring of gut microecology, characterized by a reduction in pro-inflammatory bacteria and an increase in beneficial species. Moreover, the treatments were associated with a decrease in pro-inflammatory cytokine levels in both the brain and intestines. Metabolomics analysis revealed a notable reduction in trimethylamine N-oxide and an increase in beneficial metabolites such as sphingolipids and flavonoids. These metabolic changes were correlated with improved neurological outcomes. Molecular analyses further demonstrated that AKK and AKK-Exo treatments promoted the integrity of the gut barrier, reduced systemic inflammation, and induced an anti-inflammatory M2 microglial phenotype and facilitated WM remodeling in the brain.Conclusion:This study underscores the therapeutic potential of AKK and its exosomes in promoting recovery after IS, highlighting their role in gut-brain axis modulation. Our findings suggest that AKK and AKK-Exo could serve as promising therapeutic agents for improving stroke outcomes through microbiome-based interventions.Keywords:Gut-brain axis, microbiome, ischemic stroke, Akkermansia, neuroinflammation