Risultati per: È confermato il legame tra la malattia di Alzheimer e microbiota intestinale

Objective
Helicobacter pylori infection is the most prevalent bacterial infection worldwide. Besides being the most important risk factor for gastric cancer development, epidemiological data show that infected individuals harbour a nearly twofold increased risk to develop colorectal cancer (CRC). However, a direct causal and functional connection between H. pylori infection and colon cancer is lacking.

Design
We infected two Apc-mutant mouse models and C57BL/6 mice with H. pylori and conducted a comprehensive analysis of H. pylori-induced changes in intestinal immune responses and epithelial signatures via flow cytometry, chip cytometry, immunohistochemistry and single cell RNA sequencing. Microbial signatures were characterised and evaluated in germ-free mice and via stool transfer experiments.

Results
H. pylori infection accelerated tumour development in Apc-mutant mice. We identified a unique H. pylori-driven immune alteration signature characterised by a reduction in regulatory T cells and pro-inflammatory T cells. Furthermore, in the intestinal and colonic epithelium, H. pylori induced pro-carcinogenic STAT3 signalling and a loss of goblet cells, changes that have been shown to contribute—in combination with pro-inflammatory and mucus degrading microbial signatures—to tumour development. Similar immune and epithelial alterations were found in human colon biopsies from H. pylori-infected patients. Housing of Apc-mutant mice under germ-free conditions ameliorated, and early antibiotic eradication of H. pylori infection normalised the tumour incidence to the level of uninfected controls.

Conclusions
Our studies provide evidence that H. pylori infection is a strong causal promoter of colorectal carcinogenesis. Therefore, implementation of H. pylori status into preventive measures of CRC should be considered.

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 Medical News article discusses research presented at the recent American Academy of Neurology Conference.

Stroke, Ahead of Print. Background:Respiratory and urinary tract infections are frequent complications in patients with severe stroke. Stroke-associated infection is mainly due to opportunistic commensal bacteria of the microbiota that may translocate from the gut. We investigated the mechanisms underlying gut dysbiosis and poststroke infection.Methods:Using a model of transient cerebral ischemia in mice, we explored the relationship between immunometabolic dysregulation, gut barrier dysfunction, gut microbial alterations, and bacterial colonization of organs, and we explored the effect of several drug treatments.Results:Stroke-induced lymphocytopenia and widespread colonization of lung and other organs by opportunistic commensal bacteria. This effect correlated with reduced gut epithelial barrier resistance, and a proinflammatory sway in the gut illustrated by complement and nuclear factor-κB activation, reduced number of gut regulatory T cells, and a shift of gut lymphocytes to γδT cells and T helper 1/T helper 17 phenotypes. Stroke increased conjugated bile acids in the liver but decreased bile acids and short-chain fatty acids in the gut. Gut fermenting anaerobic bacteria decreased while opportunistic facultative anaerobes, notably Enterobacteriaceae, suffered an expansion. Anti-inflammatory treatment with a nuclear factor-κB inhibitor fully abrogated the Enterobacteriaceae overgrowth in the gut microbiota induced by stroke, whereas inhibitors of the neural or humoral arms of the stress response were ineffective at the doses used in this study. Conversely, the anti-inflammatory treatment did not prevent poststroke lung colonization by Enterobacteriaceae.Conclusions:Stroke perturbs homeostatic neuro-immuno-metabolic networks facilitating a bloom of opportunistic commensals in the gut microbiota. However, this bacterial expansion in the gut does not mediate poststroke infection.

Soldi per comprare terapia genica

Eventi promossi da Aisla a Roma e Palermo

Prepared by isolating firmicutes spores from screened donors, VOWST is currently the only FDA-approved oral FMT option.

Ritardi fino a 20 anni; dai cardiologi anche l’idea di un registro

Objective
Colorectal cancer (CRC) is the third most diagnosed cancer, and requires surgical resection and reconnection, or anastomosis, of the remaining bowel to re-establish intestinal continuity. Anastomotic leak (AL) is a major complication that increases mortality and cancer recurrence. Our objective is to assess the causal role of gut microbiota in anastomotic healing.

Design
The causal role of gut microbiota was assessed in a murine AL model receiving faecal microbiota transplantation (FMT) from patients with CRC collected before surgery and who later developed or not, AL. Anastomotic healing and gut barrier integrity were assessed after surgery. Bacterial candidates implicated in anastomotic healing were identified using 16S rRNA gene sequencing and were isolated from faecal samples to be tested both in vitro and in vivo.

Results
Mice receiving FMT from patients that developed AL displayed poor anastomotic healing. Profiling of gut microbiota of patients and mice after FMT revealed correlations between healing parameters and the relative abundance of Alistipes onderdonkii and Parabacteroides goldsteinii. Oral supplementation with A. onderdonkii resulted in a higher rate of leaks in mice, while gavage with P. goldsteinii improved healing by exerting an anti-inflammatory effect. Patients with AL and mice receiving FMT from AL patients presented upregulation of mucosal MIP-1α, MIP-2, MCP-1 and IL-17A/F before surgery. Retrospective analysis revealed that patients with AL present higher circulating neutrophil and monocyte counts before surgery.

Conclusion
Gut microbiota plays an important role in surgical colonic healing in patients with CRC. The impact of these findings may extend to a vast array of invasive gastrointestinal procedures.

Eli Lilly, ‘trial su 1.200 persone, chiederemo l’autorizzazione’

Nature Communication, un gene forma le ossa dove non dovrebbe

Nature Communication, un gene forma le ossa dove non dovrebbe

Introduction
Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) is a major treatment for many haematological malignancies. The procedure has a good success rate but high transplant-related toxicity (TRM). TRM is mostly related to graft-versus-host disease (GvHD) and infectious complications. Alterations of the intestinal microbiota plays a major role in the development of allo-HSCT complications. The gut microbiota could be restored by faecal microbiota transplantation (FMT). However, there are no published randomised studies assessing the efficacy of FMT for GvHD prophylaxis.

Methods and analysis
This prospective, open-label, multi-centre, parallel-group, randomised phase-II clinical trial has been designed to assess the effect of FMT on toxicity in patients treated with myeloablative allo-HSCT for haematological malignancy. Based on Fleming’s single-stage sample size estimation procedure, the design plans to include 60 male and female patients aged 18 or over per arm, to be randomly assigned to two groups, one with and one without (control group) FMT. The primary endpoint is GvHD-free relapse-free survival rate at 1 year after allo-HSCT. Secondary endpoints are outcome measures of the impact of FMT on allo-HSCT-related morbidity and mortality (overall survival and progression-free survival at 1 and 2 years, haematological parameters, infectious complications, tolerance and safety of FMT). The primary endpoint will be evaluated according to assumptions of the single-stage Fleming design, compared between groups by a log-rank test and further investigated in a multivariate marginal structural Cox model taking into account centre effect. The proportional-hazard hypothesis will be verified using Schoenfeld’s test and by plotting residuals.

Ethics and dissemination
The local institutional review board (CPP Sud-Est II, France) issued approval on 27 January 2021. The French national authorities issued approval on 15 April 2021. The outcome of the study will be disseminated via peer-reviewed publications and at congresses.

Trial registration number
NCT04935684.