Risultati per: GUT

Objective
Ample evidence exists for the role of abnormal gut microbiota composition and increased gut permeability (‘leaky gut’) in chronic inflammation that commonly co-occurs in the gut in both obesity and diabetes, yet the detailed mechanisms involved in this process have remained elusive.

Design
In this study, we substantiate the causal role of the gut microbiota by use of faecal conditioned media along with faecal microbiota transplantation. Using untargeted and comprehensive approaches, we discovered the mechanism by which the obese microbiota instigates gut permeability, inflammation and abnormalities in glucose metabolism.

Results
We demonstrated that the reduced capacity of the microbiota from both obese mice and humans to metabolise ethanolamine results in ethanolamine accumulation in the gut, accounting for induction of intestinal permeability. Elevated ethanolamine increased the expression of microRNA-miR-101a-3p by enhancing ARID3a binding on the miR promoter. Increased miR-101a-3p decreased the stability of zona occludens-1 (Zo1) mRNA, which in turn, weakened intestinal barriers and induced gut permeability, inflammation and abnormalities in glucose metabolism. Importantly, restoring ethanolamine-metabolising activity in gut microbiota using a novel probiotic therapy reduced elevated gut permeability, inflammation and abnormalities in glucose metabolism by correcting the ARID3a/miR-101a/Zo1 axis.

Conclusion
Overall, we discovered that the reduced capacity of obese microbiota to metabolise ethanolamine instigates gut permeability, inflammation and glucose metabolic dysfunctions, and restoring ethanolamine-metabolising capacity by a novel probiotic therapy reverses these abnormalities.

Trial registration number
NCT02869659 and NCT03269032.

Pien-Tze-Huang (PZH) is a well-established Traditional Medicine with beneficial effects against inflammation and cancer. We aim to explore the chemopreventive effect of PZH in colorectal cancer (CRC) through modulating gut microbiota.

Circulation, Volume 148, Issue 8, Page 701-702, August 22, 2023.

Introduction
Chronic inflammatory diseases like rheumatoid arthritis (RA) and neurodegenerative disorders like Parkinson’s disease (PD) have recently been associated with a decreased diversity in the gut microbiome, emerging as key driver of various diseases. The specific interactions between gut-borne microorganisms and host pathophysiology remain largely unclear. The microbiome can be modulated by interventions comprising nutrition.
The aim of our clinical study is to (1) examine effects of prolonged fasting (PF) and time-restricted eating (TRE) on the outcome parameters and the immunophenotypes of RA and PD with (2) special consideration of microbial taxa and molecules associated with changes expected in (1), and (3) identify factors impacting the disease course and treatment by in-depth screening of microorganisms and molecules in personalised HuMiX gut-on-chip models, to identify novel targets for anti-inflammatory therapy.

Methods and analysis
This trial is an open-label, multicentre, controlled clinical trial consisting of a cross-sectional and a longitudinal study. A total of 180 patients is recruited. For the cross-sectional study, 60 patients with PD, 60 patients with RA and 60 healthy controls are recruited at two different, specialised clinical sites. For the longitudinal part, 30 patients with PD and 30 patients with RA undergo 5–7 days of PF followed by TRE (16:8) for a period of 12 months. One baseline visit takes place before the PF intervention and 10 follow-up visits will follow over a period of 12 months (April 2021 to November 2023).

Ethics and dissemination
Ethical approval was obtained to plan and conduct the trial from the institutional review board of the Charité-Universitätsmedizin Berlin (EA1/204/19), the ethics committee of the state medical association (Landesärztekammer) of Hessen (2021–2230-zvBO) and the Ethics Review Panel (ERP) of the University of Luxembourg (ERP 21–001 A ExpoBiome). The results of this study will be disseminated through peer-reviewed publications, scientific presentations and social media.

Trial registration number
NCT04847011.

Objectives
Diagnostic delay in cancer is a challenge in primary care. Although screening tests are effective in diagnosing some cancers such as breast, colorectal and cervical cancers, symptom-based cancer diagnosis is often difficult due to its low incidence in primary care and the influence of patient anxiety, doctor–patient relationship and psychosocial context. A general practitioner’s gut feeling for cancer may play a role in the early diagnosis of cancer in primary care where diagnostic resources are limited. The aim of this study is to summarise existing evidence about the test accuracy of gut feeling (index test) in symptomatic adult patients presenting to general practice, compared with multidisciplinary team-confirmed diagnosis of cancer (reference standard).

Design
Diagnostic accuracy review following Cochrane methods was performed.

Data sources
MEDLINE, EMBASE, Cochrane Library, the Database of Abstracts of Reviews of Effects and Medion databases.

Eligibility criteria
Cross-sectional, cohort and randomised studies of test accuracy that compared gut feeling (index test) with an appropriate cancer diagnosis (reference standard). No language or publication status restrictions were applied. We included all studies published before 25 March 2022.

Data extraction and synthesis
Methodological quality was appraised, using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria. Meta-analysis with hierarchical summary receiver operating characteristic (HSROC) models was used.

Results
Of 1286 potentially relevant studies identified, six met the inclusion criteria. For two of the six studies, data could not be extracted despite contacting authors. No studies satisfied all QUADAS-2 criteria. After meta-analysis of data from the remaining studies, the summary point of HSROC had a sensitivity of 0.40 (95% CI: 0.28, 0.53) and a specificity of 0.85 (95% CI: 0.75, 0.92).

Conclusions
Gut feeling for cancer when used in symptomatic adult patients in general practice has a relatively low sensitivity and high specificity. When the prevalence of cancer in the symptomatic population presenting in general practice exceeds 1.15%, the performance of gut feeling reaches the National Institute for Health and Care Excellence 3% positive predictive value threshold for action, which recommends urgent access to specialist care and further investigations. The findings support the continued and expanded use of gut feeling items in referral pathways.

Background
Several randomised clinical trials (RCTs) performing faecal microbiota transplantation (FMT) for the management of inflammatory bowel disease (IBD), particularly for ulcerative colitis, have recently been published, but with major variations in study design. These include differences in administered dose, route and frequency of delivery, type of placebo and evaluated endpoints. Although the overall outcomes appear to be promising, they are highly dependent on both donor and recipient factors.

Objective
To develop concensus-based statements and recommendations for the evaluation, management and potential treatment of IBD using FMT in order to move towards standardised practices.

Design
An international panel of experts convened several times to generate evidence-based guidelines by performing a deep evaluation of currently available and/or published data. Twenty-five experts in IBD, immunology and microbiology collaborated in different working groups to provide statements on the following key issues related to FMT in IBD: (A) pathogenesis and rationale, (B) donor selection and biobanking, (C) FMT practices and (D) consideration of future studies and perspectives. Statements were evaluated and voted on by all members using an electronic Delphi process, culminating in a plenary consensus conference and generation of proposed guidelines.

Results and conclusions
Our group has provided specific statements and recommendations, based on best available evidence, with the end goal of providing guidance and general criteria required to promote FMT as a recognised strategy for the treatment of IBD.

Objective
Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.

Design
Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated.

Results
The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis.

Conclusions
P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.

Circulation, Ahead of Print. BACKGROUND:Gut microbiota have been implicated in atherosclerotic disease, but their relation with subclinical coronary atherosclerosis is unclear. This study aimed to identify associations between the gut microbiome and computed tomography–based measures of coronary atherosclerosis and to explore relevant clinical correlates.METHODS:We conducted a cross-sectional study of 8973 participants (50 to 65 years of age) without overt atherosclerotic disease from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study). Coronary atherosclerosis was measured using coronary artery calcium score and coronary computed tomography angiography. Gut microbiota species abundance and functional potential were assessed with shotgun metagenomics sequencing of stool, and associations with coronary atherosclerosis were evaluated with multivariable regression models adjusted for cardiovascular risk factors. Associated species were evaluated for association with inflammatory markers, metabolites, and corresponding species in saliva.RESULTS:The mean age of the study sample was 57.4 years, and 53.7% were female. Coronary artery calcification was detected in 40.3%, and 5.4% had at least 1 stenosis with >50% occlusion. Sixty-four species were associated with coronary artery calcium score independent of cardiovascular risk factors, with the strongest associations observed forStreptococcus anginosusandStreptococcusoralissubsporalis(P

Introduction
Individuals with anorexia nervosa (AN) harbour distinct gut microbiomes compared with healthy individuals, which are sufficient to induce weight loss and anxiety-like behaviours when transplanted into germ-free mice. We hypothesise that faecal microbiome transfer (FMT) from healthy donors would help restore the gut microbiome of individuals with AN, which in turn, may aid patient recovery.

Methods
We aim to conduct an open-label pilot study in 20 females aged 16–32 years in Auckland, New Zealand who meet the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria for AN and have a body mass index 13–19 kg/m2. We will recruit four healthy, lean, female donors, aged 18–32 years, who will undergo extensive clinical screening prior to stool donation. Faecal microbiota will be harvested from donors and double encapsulated in delayed release, acid-resistant capsules. All participants will receive a single course of 20 FMT capsules (five from each donor) which they can choose to take over two or four consecutive days. Stool and blood samples will be collected from participants over a period of 3 months to assess their gut microbiome profile, metabolome, levels of intestinal inflammation and nutritional status. Our primary outcome is a shift in the gut microbiome composition at 3 weeks post-FMT (Bray-Curtis dissimilarity). We will also monitor participants’ body composition (whole-body dual-energy X-ray absorptiometry scans), eating disorder psychopathology, mental health and assess their views on, and tolerability of, treatment. All adverse events will be recorded and reviewed by an independent data monitoring committee.

Ethics and dissemination
Ethics approval was provided by the Central Health and Disability Ethics Committee (Ministry of Health, New Zealand, 21/CEN/212). Results will be published in peer-reviewed journals and presented to both scientific and consumer group audiences.

Trial registration number
ACTRN12621001504808.

Objective
To explore the interplay between dietary modifications, microbiome composition and host metabolic responses in a dietary intervention setting of a personalised postprandial-targeting (PPT) diet versus a Mediterranean (MED) diet in pre-diabetes.

Design
In a 6-month dietary intervention, adults with pre-diabetes were randomly assigned to follow an MED or PPT diet (based on a machine-learning algorithm for predicting postprandial glucose responses). Data collected at baseline and 6 months from 200 participants who completed the intervention included: dietary data from self-recorded logging using a smartphone application, gut microbiome data from shotgun metagenomics sequencing of faecal samples, and clinical data from continuous glucose monitoring, blood biomarkers and anthropometrics.

Results
PPT diet induced more prominent changes to the gut microbiome composition, compared with MED diet, consistent with overall greater dietary modifications observed. Particularly, microbiome alpha-diversity increased significantly in PPT (p=0.007) but not in MED arm (p=0.18). Post hoc analysis of changes in multiple dietary features, including food-categories, nutrients and PPT-adherence score across the cohort, demonstrated significant associations between specific dietary changes and species-level changes in microbiome composition. Furthermore, using causal mediation analysis we detect nine microbial species that partially mediate the association between specific dietary changes and clinical outcomes, including three species (from Bacteroidales, Lachnospiraceae, Oscillospirales orders) that mediate the association between PPT-adherence score and clinical outcomes of hemoglobin A1c (HbA1c), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Finally, using machine-learning models trained on dietary changes and baseline clinical data, we predict personalised metabolic responses to dietary modifications and assess features importance for clinical improvement in cardiometabolic markers of blood lipids, glycaemic control and body weight.

Conclusions
Our findings support the role of gut microbiome in modulating the effects of dietary modifications on cardiometabolic outcomes, and advance the concept of precision nutrition strategies for reducing comorbidities in pre-diabetes.

Trial registration number
NCT03222791.

We read with great interest the paper by Ha et al1 demonstrating that circulating levels of serotonin (5-hydroxytryptamine, 5-HT) are increased in COVID-19 and correlate with disease severity and gastrointestinal symptoms such as diarrhoea. Another recent paper by Lin et al2 in this journal demonstrated that diarrhoea is the most common GI symptom in patients with COVID-19. Almost all 5-HT in our body is produced by enterochromaffin (EC) cells within the epithelium of the GI tract, which constitute approximately half of all enteroendocrine (EE) cells. Gut-derived 5-HT modulates gut peristalsis and exacerbates inflammatory responses by acting as a chemotactic molecule for various immune cells and by triggering cytokine release.3 While most gut epithelial cell types are susceptible to SARS-CoV-2 infection, EE cells have the greatest proportion of cells infected at 12 hours after viral exposure.4 In addition, the use of selective…

Clinical presentation A 63-year-old man presented with an increasing number of pruritic, light to dark brown papules affecting his scalp, forehead and trunk (figure 1). The skin lesions started growing approximately 2 years prior. Clinical diagnosis of seborrhoeic keratoses (SK) was confirmed by histopathological examination (figure 2). Work-up of new intermittent dragging pain localised on the lower right abdominal quadrant showed well-differentiated neuroendocrine tumours (G1; somatostatin receptor 2a (SSTR2A) positive) of the ileum and the appendix. The ileum tumour had a diameter of 16 mm, with muscularis propria infiltration, invasion of lymphatic as well as blood vessels, and metastases in 3 out of 14 examined mesenteric lymph nodes (pT2pN2 (3/14) G1 L1 Pn0 R0). The appendix tumour had a diameter of 3 mm, muscularis propria infiltration and without vessel invasion (pT1a/pT1 G1 L0 V0 Pn0 R0). Immunohistochemical SK staining with SSTR2A was negative (

We read with interest the recent article by Ng et al. (Gut, 2022; 71:910–8), who reported inhibition of the gut microbiota trajectory in patients with autism spectrum disorder.1 Similarly, the human gut microbiota ages in adults.2 3 Transplantation of gut microbes from elderly hosts, compared with their younger counterparts, deteriorates recipients’ age-related metabolic alternations.4 5 However, the gut microbiota in humans could differ in its pace of ageing, namely, accelerated or delayed microbiota ageing, even among those with similar chronological ages (figure 1A); this process is analogous to biological ageing.6 Therefore, we wondered whether the gut microbiota ageing trajectory could be used as a biomarker for metabolic diseases in adults. We analysed the gut microbiota compositions of 6376 participants of a population-level survey7 with Quantitative Insights Into Microbial Ecology (QIIME),8 among…

This metabolome-wide association study evaluates the association of metabolic factors and the human gut microbiome and metabolome with major depressive disorder.