Risultati per: GUT

Does AD change the gut microbiome, or does the gut microbiome influence risk for developing AD?

Dietary fibers are mainly fermented by the gut microbiota, but their roles in colorectal cancer (CRC) are largely unclear. Here, we investigated the associations of different fibers with colorectal tumorigenesis in mice.

This case-control study compares differences in the fecal microbiota—including overall diversity, composition, and putative function—between control participants and patients with melanoma and between patients with early- and late-stage melanoma.

The gut contains approximately 100 trillion commensal microorganisms, including viruses, archaea, bacteria, and unicellular eukaryotes that influence the development and function of the human neurological, immunological, and digestive systems from birth through adulthood. These collective microbes and their genes comprise the gut microbiome, which has gained clinical interest in many specialties as a diagnostic and potential therapeutic tool for several diseases and malignant neoplasms. The bacterial component of the gut microbiome is the most well-characterized and can be studied in a culture-independent manner using 16S ribosomal RNA sequencing. Alpha diversity describes the richness (number of unique species) in a single sample. Beta diversity describes differences between population samples. Dysbiosis describes a deviation from normal composition or metabolic activity.

Introduction
Excess body weight is associated with a state of low-grade chronic inflammation and alterations of the gut microbiome. Powdered meal replacements (PMR) have been shown to be an effective strategy for weight management; however, their effect on inflammation and the gut microbiome remains unclear. The aim of this 12-week randomised control clinical trial is to investigate the effects of PMR consumption, here given as a soy-yoghurt-honey formula, on inflammation, gut microbiome and overall metabolism in individuals with excessive body weight.

Methods and analysis
Healthy adults with excess body weight (n=88) are being recruited and randomly assigned to one of the following groups: (1) Control group (CON): maintaining usual diet for 12 weeks, or (2) PMR group: replacing morning and afternoon snacks daily with a PMR for 12 weeks. Participants are asked to maintain body weight throughout the study and fill out a journal with information about PMR consumption, body weight, food intake, appetite sensations and medications. Three study visits are required: baseline, week 6 and week 12. Outcome measures include systemic inflammatory biomarkers, gut microbiome composition, metabolic blood markers, host energy metabolism, body composition, appetite sensations and host gene expression profile.

Ethics and dissemination
This research protocol was approved by the University of Alberta Ethics Board (Pro00070712) and adheres to the Canadian Tri-Council Policy statement on the use of human participants in research. Procedures and potential risks are fully discussed with participants. Study findings will be disseminated in peer-reviewed journals, conference presentations and social media.

Trial registration number
NCT03235804.

Recently, we read the article by Ng et al with great interest,1 which identified several gut microbiota harbour the potential to improve immune response and reduce adverse events following COVID-19 vaccines, and demonstrated that gut microbiota has the potential to complement the effectiveness of vaccines. Together with several recent studies, gut microbiota plays a key role in modulating immune responses of vaccination2–4 and is related to the severity of COVID-19 patients,5 6 however, the comprehensive assessment of host’s response, particularly the role of gut microbiota in antibodies production is limited and should be seriously considered because the vaccination of SARS-CoV-2 is the most promising approach for curbing the COVID-19 pandemic.4 7 Therefore, we recruited 30 young volunteers (20–23 years old), including 15 male and 15 female volunteers, and collected 143 faecal and 120…

Objectives
Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by the Orthohepadnavirus genus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis.

Design
HBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.
C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed on in vitro models of the gut barrier. HBx-silencing experiments were performed in vitro and in vivo.

Results
HBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotype in vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunity ex vivo and in vivo.

Conclusion
This study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

Microbiota are a source of low-grade inflammation during obesity and contribute to insulin resistance and poor blood glucose control among other mechanisms in the progression of type 2 diabetes.1 Nearly all bacteria that reside within the host are found in the intestine, but it is not yet clear how microbiota are a source of inflammation in the circulation or metabolic tissues during obesity. A key knowledge gap is understanding how obesity or certain diets promote gut barrier dysfunction that allows increased permeability for bacteria or bacterial components that can engage immune response and promote inflammation-induced metabolic dysfunction. Metabolic endotoxaemia is the key example of a bacterial source of inflammation. Obesity or diet-induced increases in lipopolysaccharides (LPS or endotoxin), that escape the gut lumen, penetrate the intestinal barrier and enter into the host circulation, cells and tissues. This low-level increase in LPS activate toll-like receptor 4, increase inflammation…

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.

A Southeast Asian man in his early 20s with no medical history presented with persistent abdominal pain and nausea for 3 weeks. He reported no recent sick contacts and no travel in the past 5 years since arrival to the USA. Physical examination was notable for right lower quadrant tenderness. CT of the abdomen and pelvis showed hyperaemia and fat stranding near the terminal ileum and cecum, concerning for appendicitis. He underwent laparoscopic appendectomy with pathology showing acute granulomatous appendicitis. Bacterial, fungal and acid-fast bacilli (AFB) stains were negative. Given the presence of granulomas, interferon gamma release assay and ACE levels were obtained which were unremarkable. HIV-1/2 testing was negative. He unfortunately developed recurrent abdominal pain 4 weeks postoperatively. CT imaging at that time showed pelvic fluid collections, treated empirically with amoxicillin–clavulanic acid for presumed abscesses. The collections persisted despite additional antibiotic rounds, and he eventually presented to the…

We read with interest the study by Kartal et al1 showing that the gut-microbiota-derived biomarkers for disease stratification are often shared by subjects across disease cohorts. Here, we confirmed their observations with findings from a newly diagnosed natural killer/T-cell lymphoma (NKTCL) cohort, in which the gut biomarkers were significantly overlapped with those of multiple disease cohorts and consistently enriched/depleted in subjects with those diseases. Importantly, many of the shared biomarkers were remarkably associated with patient outcomes in our cohort, implying that they may have broad prognostic values in multiple diseases. ‘Microbiota-gut-lymphoma axis’ represents a fascinating avenue of microbiota-mediated lymphomagenesis and intervention opportunity,2 but the implications of gut microbiota in NKTCL remain enigmatic. To identify gut microbiota-derived diagnostic biomarkers for NKTCL, we recruited a discovery cohort consisting of 30 treatment-naïve patients and 20 healthy controls (HCs), and a validation cohort, including 12 patients and 13 HCs,…

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.