Risultati per: GUT

Introduction
Autism (formally autism spectrum disorder) encompasses a group of complex neurodevelopmental conditions, characterised by differences in communication and social interactions. Co-occurring chronic gastrointestinal symptoms are common among autistic individuals and can adversely affect their quality of life. This study aims to evaluate the efficacy of oral encapsulated faecal microbiome transfer (FMT) in improving gastrointestinal symptoms and well-being among autistic adolescents and adults.

Methods and analysis
This double-blind, randomised, placebo-controlled trial will recruit 100 autistic adolescents and adults aged 16–45 years, who have mild to severe gastrointestinal symptoms (Gastrointestinal Symptoms Rating Scale (GSRS) score ≥2.0). We will also recruit eight healthy donors aged 18–32 years, who will undergo extensive clinical screening. Recipients will be randomised 1:1 to receive FMT or placebo, stratified by biological sex. Capsules will be administered over two consecutive days following an overnight bowel cleanse with follow-up assessments at 6, 12 and 26 weeks post-treatment. The primary outcome is GSRS score at 6 weeks. Other assessments include anthropometry, body composition, hair cortisol concentration, gut microbiome profile, urine/plasma gut-derived metabolites, plasma markers of gut inflammation/permeability and questionnaires on general well-being, sleep quality, physical activity, food diversity and treatment tolerability. Adverse events will be recorded and reviewed by an independent data monitoring committee.

Ethics and dissemination
Ethics approval for the study was granted by the Central Health and Disability Ethics Committee on 24 August 2021 (reference number: 21/CEN/211). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.

Trial registration number
ACTRN12622000015741.

Introduction
Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC).

Methods/design
This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1–3 and one meal/day in months 4–6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1–2 pounds per week.

Ethics and dissemination
The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563).

Trial registration number
NCT04780477.

Stroke, Volume 55, Issue Suppl_1, Page A108-A108, February 1, 2024. Neonatal hypoxic ischemic encephalopathy (HIE) increases the risk for attention deficit disorder and autism spectrum disorders in children. Perturbations in the gut microbiome are associated with behavioral changes in pre-clinical models of neurological injury and development. However, the role of the gut microbiome in behavior after HIE has not been investigated. Also, the therapeutic potential of gut microbiota modification after HIE remains unexplored. We hypothesize that altering the gut microbiome after HIE can improve chronic behavioral deficits in mice. The Rice Vannucci Model (RVM) was used to model HIE on 9-day old C57BL/6 mice. 2 months after injury, fecal samples were collected for 16s rRNA sequencing and behavioral tests were performed. We treated HIE and sham mice with fecal microbiota transfers (FMT) from naïve donors. To determine if the microbiota from HIE mice drives behavioral deficits, we also gave FMT from HIE or sham donors into naïve. Tests were repeated 1 and 3 months after FMT, and mice were sacrificed at 5 months of age. 2 months after injury, baseline open field tests revealed a hyperactive phenotype in HIE mice. There was increased mean velocity, distance moved, and cumulative time in border coupled with decreased cumulative time in center compared to shams (P&lt0.0001, P&lt0.0001, P=0.0168, P=0.025; T test, two cohorts, n=14-18). PCoA on calculated weighted UniFrac distances reveal a significant difference in β-diversity in males (P=0.015) and females (P=0.033) at 2 months. At 5 months, HIE mice with a naïve FMT had normalization of their hyperactive phenotype, measured by a reduction in mean velocity and distance moved (P=0.028 and P=0.0322; Repeated Measures One-way ANOVA, Dunnett’s test), while sham mice had no change. Surprisingly, naïve mice given a FMT from HIE donors became hypoactive with reduced mean velocity and distance moved (P=0.0004 and P=0.0004; Mixed effects Model, Tukey’s test, 2 cohorts n=6-11), while Naive mice with sham FMT had no change. In conclusion, gut microbiota modification through FMT in adult mice with a history of HIE reduced the severity of their hyperactive phenotype. Conversely, FMT from HIE mice into naïve mice induced mild behavioral changes but did not reproduce the hyperactivity seen in HIE mice.

Stroke, Volume 55, Issue Suppl_1, Page ATMP118-ATMP118, February 1, 2024. The microbiome plays a significant role in influencing general health. A disruption of the gut biome homeostasis, dysbiosis, can be both the effect of disease or a precondition. The maternal biome has been shown to play a vital role in offspring brain and immune development by shaping the metabolic environment for the embryo. Therefore, an aged dysbiotic maternal biome may increase stroke risk factors among offspring and additionally, worsen stroke outcome. Young female C57B6 mice 3-month (M) of age had their host gut bacteria cleared via antibiotic treatment prior to recolonization via fecal microbiome transplants from 3M control, and 14M middle aged female mice. After breeding, the subsequent offspring was aged to 14 months, followed by behavioral tests, glucose tolerance, prior to a transient 60-minute middle cerebral artery occlusion (MCAO or sham surgery). The maternal biome had a significant effect on offspring biome at 2M, 6M and 9M of age, shifting the beta-diversity of females significantly (p=0.01). Once the offspring had been subjected to a 60 min MCAO, a spontaneous recovery was observed in NDS scores in all females and in the control males, but not in males from dysbiotic mothers, suggesting that male stroke outcome is negatively affected by dysbiotic mothers. The maternal microbiome has a significant impact on offspring biome composition and health. Mice from mothers with aged microbiome exhibited sex specific early life motor function and cognitive impairment. Additionally, male offspring from dysbiotic mothers have a worsened stroke outcome.

Disorders of gut-brain interaction (DGBIs) are characterized by chronic gastrointestinal symptoms, in the absence of abnormal endoscopic or radiologic findings or objective biomarkers that can be identified during routine clinical evaluation. The assessment of the symptom pattern and severity therefore is the key modality to evaluate the presence, impact and evolution of these conditions, both for clinical and regulatory purposes. Patient-reported outcomes (PROs) are structured symptom assessment questionnaires designed to evaluate symptom patterns, quantify severity of symptoms, and evaluate response to treatment at follow-up.

The development of real-time and non-invasive methods for monitoring gut health, signaling, and inflammatory status has the potential to transform the diagnosis, treatment, management, and drug development of numerous pathologies of the gut. Inflammatory bowel disease (IBD) represents one such area of large unmet clinical and pharmaceutical needs as it affects a large proportion of the population, has continued to increase in prevalence over time, and can have devastating consequences when not appropriately diagnosed and managed.

The understanding of the role of intestinal bacteria in various intestinal diseases has been limited due to the lack of suitable in vitro models. However, recent advancements in Gut-on-a-Chip culture technology provide a promising avenue for exploring complex interactions between intestinal epithelium and bacteria. In this study, we aimed to create a microfluidic Gut-on-a-Chip co-culture system using dogs as a model. Dogs share similarities with humans in terms of intestinal disease pathophysiology, clinical presentations, and intestinal microbiome, making them a relevant model for various intestinal diseases, including inflammatory bowel disease (IBD).

Inflammatory bowel disease (IBD) is a spectrum of disorders, namely Crohn’s Disease (CD) and Ulcerative Colitis (UC), characterized by distinct patterns of intestinal inflammation, a dysregulated intestinal immune response, and an altered gut microbiota. Given the growing number of new IBD diagnoses (70,000 new cases reported each year) and the inconsistent results of current treatment options, there is a major unmet need to understand IBD pathophysiology to develop more effective treatments. Previous reports indicate that IBD patients have an altered gut microbiota that can influence the development of inflammatory innate and adaptive immune cells that cause intestinal tissue damage and drive IBD pathogenesis.

Fiber free exclusive enteral nutrition (EEN) is an effective steroid-sparing treatment used to induce clinical remission in children with Crohn’s disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. We have generated a novel mouse strain that harbors mutations in two CD susceptibility genes (i.e, NOD2 and CYBB) and found that these mice spontaneously develop an early-onset (4 weeks of age), TH1-type gut inflammation, that closely recapitulates the human disease when exposed to a specific murine microbiota.

Objectives
This study aimed to pool the efficacy in bowel movement and explore the change of gut microbiota on adult functional constipated patients after probiotics-containing products treatment.

Design
Systematic review and meta-analysis.

Data sources
PubMed, Cochrane Library for published studies and ClinicalTrials.gov for ‘grey’ researches were independently investigated for randomised controlled trials up to November 2022.

Eligibility criteria, data extraction and synthesis
The intervention was probiotics-containing product, either probiotics or synbiotics, while the control was placebo. The risk of bias was conducted. The efficacy in bowel movement was indicated by stool frequency, stool consistency and Patient Assessment of Constipation Symptom (PAC-SYM), while the change of gut microbiota was reviewed through α diversity, β diversity, change/difference in relative abundance and so on. The subgroup analysis, sensitivity analysis and random-effect meta-regression were conducted to explore the heterogeneity. The Grading of Recommendations Assessment Development and Evaluation was conducted to grade the quality of evidence.

Results
17 studies, comprising 1256 participants, were included with perfect agreements between two researchers (kappa statistic=0.797). Compared with placebo, probiotics-containing products significantly increased the stool frequency (weighted mean difference, WMD 0.93, 95% CI 0.47 to 1.40, p=0.000, I²=84.5%, ‘low’), improved the stool consistency (WMD 0.38, 95% CI 0.05 to 0.70, p=0.023, I²=81.6%, ‘very low’) and reduced the PAC-SYM (WMD –0.28, 95% CI: –0.45 to –0.11, p=0.001, I²=55.7%, ‘very low’). In subgroup analysis, synbiotics was superior to probiotics to increase stool frequency. Probiotics-containing products might not affect α or β diversity, but would increase the relative abundance of specific strain.

Conclusions
Probiotics-containing products, significantly increased stool frequency, improved stool consistency, and alleviated functional constipation symptoms. They increased the relative abundance of specific strain. More high-quality head-to-head randomised controlled trials are needed.

Circulation, Volume 149, Issue 3, Page 276-276, January 16, 2024.

Circulation, Volume 149, Issue 3, Page 274-275, January 16, 2024.

Objective
The gut virome is a dense community of viruses inhabiting the gastrointestinal tract and an integral part of the microbiota. The virome coexists with the other components of the microbiota and with the host in a dynamic equilibrium, serving as a key contributor to the maintenance of intestinal homeostasis and functions. However, this equilibrium can be interrupted in certain pathological states, including inflammatory bowel disease, causing dysbiosis that may participate in disease pathogenesis. Nevertheless, whether virome dysbiosis is a causal or bystander event requires further clarification.

Design
This review seeks to summarise the latest advancements in the study of the gut virome, highlighting its cross-talk with the mucosal microenvironment. It explores how cutting-edge technologies may build upon current knowledge to advance research in this field. An overview of virome transplantation in diseased gastrointestinal tracts is provided along with insights into the development of innovative virome-based therapeutics to improve clinical management.

Results
Gut virome dysbiosis, primarily driven by the expansion of Caudovirales, has been shown to impact intestinal immunity and barrier functions, influencing overall intestinal homeostasis. Although emerging innovative technologies still need further implementation, they display the unprecedented potential to better characterise virome composition and delineate its role in intestinal diseases.

Conclusions
The field of gut virome is progressively expanding, thanks to the advancements of sequencing technologies and bioinformatic pipelines. These have contributed to a better understanding of how virome dysbiosis is linked to intestinal disease pathogenesis and how the modulation of virome composition may help the clinical intervention to ameliorate gut disease management.