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

Mangiano tanto ma restano magri, problema in centraline cellule

Una piena riconferma per il Segretario Generale Silvestro Scotti e il suo Esecutivo Nazionale, con l’ingresso in squadra di una donna sotto i quarant’anni come prevedeva lo statuto nella modifica voluta nel corso del mandato dall’Esecutivo uscente

We read with great interest the recent article by Yeoh et al, demonstrating an altered stool microbiome composition in patients with COVID-19 compared with controls, with greater dysbiosis correlating with elevated inflammatory markers.1 Additionally, dysbiosis was seen after disease resolution.1 To our knowledge, gut microbiome studies in young children with COVID-19 have not been reported. Critically, the developing gut microbiome of very young children differs from adults and establishes immune and inflammatory pathways.2 3 Moreover, children with COVID-19 can subsequently develop autoimmune and autoinflammatory diseases including Multisystem Inflammatory Syndrome in Children (MIS-C)4 5, which may in part be microbiome mediated, given recent findings by Yeoh et al.1 It is difficult to study this in young children, as many with SARS-CoV-2 infection are asymptomatic and rarely tested.6 To address this, knowing that SARS-CoV-2 can…

Objective
This study is to investigate the role of gut dysbiosis in triggering inflammation in the brain and its contribution to Alzheimer’s disease (AD) pathogenesis.

Design
We analysed the gut microbiota composition of 3xTg mice in an age-dependent manner. We generated germ-free 3xTg mice and recolonisation of germ-free 3xTg mice with fecal samples from both patients with AD and age-matched healthy donors.

Results
Microbial 16S rRNA sequencing revealed Bacteroides enrichment. We found a prominent reduction of cerebral amyloid-β plaques and neurofibrillary tangles pathology in germ-free 3xTg mice as compared with specific-pathogen-free mice. And hippocampal RNAseq showed that inflammatory pathway and insulin/IGF-1 signalling in 3xTg mice brain are aberrantly altered in the absence of gut microbiota. Poly-unsaturated fatty acid metabolites identified by metabolomic analysis, and their oxidative enzymes were selectively elevated, corresponding with microglia activation and inflammation. AD patients’ gut microbiome exacerbated AD pathologies in 3xTg mice, associated with C/EBPβ/asparagine endopeptidase pathway activation and cognitive dysfunctions compared with healthy donors’ microbiota transplants.

Conclusions
These findings support that a complex gut microbiome is required for behavioural defects, microglia activation and AD pathologies, the gut microbiome contributes to pathologies in an AD mouse model and that dysbiosis of the human microbiome might be a risk factor for AD.

We read with interest the work by Camilleri and Vella1 reporting the potential role of ‘leaky gut’ or reduced barrier function in some pathophysiological states. The detrimental effects of dietary emulsifiers on host intestinal barrier have also been evaluated.1–3 However, their role on promoting skin-related diseases and whether modulation of the microbiota can reversibly impact their underlying chemical effects are unknown. Herein, we showed that a common emulsifier, polysorbate-80 (P80), together with a soybean-deprived diet, promoted alopecia in mice. Importantly, the pathogenic process was exacerbated by antibiotics through aggravating gut dysbiosis and reversed following faecal microbiota transplantation (FMT) or administration of a targeted probiotic (Bifidobacterium longum HK003) isolated from faeces of healthy subjects (figures 1A–C and 2A,B). P80 and antibiotics-treated mice developed severe alopecia with large balding patches. Antibiotics exacerbated the microbial compositions induced by P80 including…

We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and validate the results with follow-up, Japanese 4D microbiome cohort, and non-Japanese datasets.

Stroke, Ahead of Print. BACKGROUND:Species-specific differences in astrocytes and their Alzheimer disease-associated pathology may influence cellular responses to other insults. Herein, human glial chimeric mice were generated to evaluate how Alzheimer disease predisposing genetic background in human astrocytes contributes to behavioral outcome and brain pathology after cortical photothrombotic ischemia.METHODS:Neonatal (P0) immunodeficient mice of both sexes were transplanted with induced pluripotent stem cell–derived astrocyte progenitors from Alzheimer disease patients carryingPSEN1exon 9 deletion (PSEN1ΔE9), with isogenic controls, with cells from a healthy donor, or with mouse astrocytes or vehicle. After 14 months, a photothrombotic lesion was produced with Rose Bengal in the motor cortex. Behavior was assessed before ischemia and 1 and 4 weeks after the induction of stroke, followed by tissue perfusion for histology.RESULTS:Open field, cylinder, and grid-walking tests showed a persistent locomotor and sensorimotor impairment after ischemia and female mice had larger infarct sizes; yet, these were not affected by astrocytes withPSEN1ΔE9 background. Staining for human nuclear antigen confirmed that human cells successfully engrafted throughout the mouse brain. However, only a small number of human cells were positive for astrocytic marker GFAP (glial fibrillary acidic protein), mostly located in the corpus callosum and retaining complex human-specific morphology with longer processes compared with host counterparts. While host astrocytes formed the glial scar, human astrocytes were scattered in small numbers close to the lesion boundary. Aβ (beta-amyloid) deposits were not present inPSEN1ΔE9 astrocyte-transplanted mice.CONCLUSIONS:Transplanted human cells survived and distributed widely in the host brain but had no impact on severity of ischemic damage after cortical photothrombosis in chimeric mice. Only a small number of transplanted human astrocytes acquired GFAP-positive glial phenotype or migrated toward the ischemic lesion forming glial scar.PSEN1ΔE9 astrocytes did not impair behavioral recovery after experimental stroke.

Introduction
Gut microbiota (GM) appears critical for gastrointestinal symptoms, but whether alterations in GM are associated with increased risk of postoperative gastrointestinal dysfunction (POGID) in older patients with colon cancer (CC) undergoing elective colon resection remains unclear.

Methods and analysis
This study aims to prospectively recruit 284 elderly patients with CC undergoing elective colon resection. GM of fresh faeces specimens is characterised using 16S rRNA gene sequencing. Data are collected preoperatively, daily postoperatively during the in-hospital stay, and follow-up visits are scheduled four times within 30 days after discharge. Associations with POGID will be investigated using logistic regression models to calculate ORs with 95% CIs. The models include the adjustment for age, sex, frequency of spicy diet, coffee drinking and tea drinking, tobacco and alcohol history, diabetes, obesity, gastroenteritis, preoperative gut microbial composition. Furthermore, we will use joint modelling for longitudinal data to study several outcome variables simultaneously.

Ethics and dissemination
This study was approved by the Institutional Review Board of West China Hospital, Sichuan University (IRB Number: 20201334). The results will be disseminated through peer-reviewed publications or conference presentations.

Trial registration number
It has been registered in PROSPERO, number CRD42019145032. It has been registered in the Chinese clinical trial registry, number ChiCTR2100043646.

Comunicato del 07/09/2022 n°37

Objective
Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis.

Design
The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry.

Results
L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum-treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size

This multicenter cohort study analyzes the associations between intratumoral microbiota and prognostication in patients with nasopharyngeal carcinoma.

Objective
Reducing FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) can be clinically beneficial in IBS but the mechanism is incompletely understood. We aimed to detect microbial signatures that might predict response to the low FODMAP diet and assess whether microbiota compositional and functional shifts could provide insights into its mode of action.

Design
We used metagenomics to determine high-resolution taxonomic and functional profiles of the stool microbiota from IBS cases and household controls (n=56 pairs) on their usual diet. Clinical response and microbiota changes were studied in 41 pairs after 4 weeks on a low FODMAP diet.

Results
Unsupervised analysis of baseline IBS cases pre-diet identified two distinct microbiota profiles, which we refer to as IBSP (pathogenic-like) and IBSH (health-like) subtypes. IBSP microbiomes were enriched in Firmicutes and genes for amino acid and carbohydrate metabolism, but depleted in Bacteroidetes species. IBSH microbiomes were similar to controls. On the low FODMAP diet, IBSH and control microbiota were unaffected, but the IBSP signature shifted towards a health-associated microbiome with an increase in Bacteroidetes (p=0.009), a decrease in Firmicutes species (p=0.004) and normalisation of primary metabolic genes. The clinical response to the low FODMAP diet was greater in IBSP subjects compared with IBSH (p=0.02).

Conclusion
50% of IBS cases manifested a ‘pathogenic’ gut microbial signature. This shifted towards the healthy profile on the low FODMAP diet; and IBSP cases showed an enhanced clinical responsiveness to the dietary therapy. The effectiveness of FODMAP reduction in IBSP may result from the alterations in gut microbiota and metabolites produced. Microbiota signatures could be useful as biomarkers to guide IBS treatment; and investigating IBSP species and metabolic pathways might yield insights regarding IBS pathogenic mechanisms.