Risultati per: GUT

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

Introduction
Yeast beta-glucan (YBG) are recognised for enhancing the immune system by activating macrophages, a key defence mechanism. Given the global prevalence and impact of upper respiratory tract infections (URTIs) on productivity and healthcare costs, YBG has shown promise as a potential therapeutic and preventive strategy for recurrent respiratory tract infections. However, little is known regarding the efficacy of YBG at lower dosages in relation to URTI, fatigue, immune response and uncertainties of how they affect the gut microbiota composition.

Methods and analysis
This 12-week randomised, double-blinded, placebo control, parallel-group clinical trial aims to evaluate the efficacy of YBG 1,3/1,6 on respiratory tract infection, fatigue, immune markers and gut health among adults with moderate stress. The study involves 198 adults aged 18–59 years with moderate stress levels as assessed using Perceived Stress Scale 10 (score 14–26) and Patient Health Questionnaire 9 (score ≥9); and had symptoms of common colds for the past 6 months as assessed using Jackson Cold Scale. These participants will be randomised into three groups, receiving YBG 1,3/1,6 at either 120 mg, 204 mg or a placebo. The outcomes measures include respiratory infection symptoms, fatigue, mood state and quality of life assessed using Wisconsin Upper Respiratory Symptoms Scale, Multidimensional Fatigue Inventory, Profile of Mood State and Short Form 36 Health Survey Questionnaire, respectively. In addition, full blood analysis and assessment of immune, inflammatory and oxidative stress biomarkers will be taken. Secondary outcome includes gut microbiota analysis using stool samples via 16S rRNA sequencing.

Ethics and dissemination
The research protocol of the study was reviewed and approved by the Research Ethics Committee of Universiti Kebangsaan Malaysia (UKM/PPI/111/8/JEP-2023–211). The findings will be disseminated to participants, healthcare professionals and researchers via conference presentations and peer-reviewed publications.

Trial registration number
ISRCTN48336189

In their review, Inamura et al.1 emphasise the need for prospective cohort studies to establish the role of the microbiome as an essential exposome in tumourigenesis. However, establishing the relationship between gut microbiota and sporadic colorectal cancer (CRC) is challenging due to the extended time required for precancerous lesions to develop into cancer.2 Thus, we believe the rapid onset of CRC in patients with familial adenomatous polyposis (FAP) presents a unique opportunity for longitudinal research into the role of the gut microbiome in colorectal carcinogenesis. Previous studies have demonstrated the association of the gut microbiome and metabolites with tumourigenesis in sporadic CRC.3–5 Here, with informed consent and institutional review board approval, we collected stool samples from 130 FAP patients who had not undergone surgery but had undergone repetitive intensive endoscopic reduction of polyp burden (IER)6 7

Background
The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity.

Objective
To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues.

Design
Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose).

Results
Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes.

Conclusion
These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.Cite Now

Introduction
Although evidence exists on the impact of microbiota on pregnancy outcomes in many high-resource settings, there is a lack of research in many low-resource settings like Ethiopia. This study aims to fill this gap by studying the gut and vaginal microbiota changes throughout pregnancy and assess how these changes relate to pregnancy outcomes among a cohort of pregnant women in eastern Ethiopia.

Methods and analysis
Vaginal and stool samples will be collected using DNA/RNA Shield Collection kits three times starting at 12–22 weeks, 28–36 weeks and at birth (within 7 days). Postnatally, newborns’ skin swabs (at birth) and rectal swabs will be obtained until 2 years of age. Moreover, breast milk samples at birth and 6 months and environmental samples (water, indoor air and soil) will be collected at enrolment, birth, 6, 12 and 24 months post partum. DNA will be extracted using Roche kits. Metagenomic sequencing will be performed to identify metataxonomic profiling and assess variations in microbial profiles, and α and β diversity of the microbiota. Information on socioeconomic, behavioural, household and biological factors will be collected at enrolment. The collected data will be coded, entered into EpiData 3.1 and analysed using Stata 17.

Ethics and dissemination
The Institutional Health Research Ethics Review Committee (Ref No. IHRERC/033/2022) of Haramaya University, Ethiopia has approved this study ethically. Written informed consent regarding the study and sample storage for biobanking will be obtained from all participants. Results will be published in international peer-reviewed journals, and summaries will be provided to the study funders. Clinical study data will be submitted to Data Compass (https://datacompass.lshtm.ac.uk/), and molecular profiles of the microbiome and whole-genome sequences will be submitted to the European Nucleotide Archive (https://www. ebi.ac.uk/ena). Requests for data should be directed to daberaf@gmail.com. The decision to share data will be made by the study steering committee under the College of Health and Medical Sciences, Haramaya University, Ethiopia.