Risultati per: GUT

Circulation, Volume 146, Issue Suppl_1, Page A12294-A12294, November 8, 2022. Introduction:Modest experimental and human evidence implicate a role for physical activity or sedentary lifestyle in the perturbation of the gut microbiome, yet large human studies are lacking.Methods:This study included 1846 US Hispanic/Latino adults without diabetes aged 23-82 years (mean age 48 years, 49% women) with gut microbiome data by shotgun sequencing of stools and accelerometer-measured moderate-to-vigorous physical activity (MVPA) and sedentary time from the HCHS/SOL population based cohort (2014-2017). We examined associations of MVPA and sedentary time with gut microbial features – Bray-Curtis dissimilarity by PERMANOVA, and alpha diversity and centered log ratio transformed relative abundance of species and KEGG pathway modules by a linear regression accounting for the complex survey design.Results:Prolonged sedentary time was associated with higher Shannon index (0.03 per 1 hr of sedentary time, SE=0.02, P=0.077) and Bray-Curtis dissimilarity (R2=0.32%, P

Accumulating evidence not only supports the functional role of the gut microbiome in cancer development and progression but also its role in defining the efficacy and toxicity of chemotherapeutic agents (5-fluorouracil, CTX, Irinotecan, Oxaliplatin, Gemcitabine, Methotrexate) and immunotherapeutic (anti-PD-L1/ anti-PD-1 and anti-CTLA-4) compounds. This evidence is supported in numerous in-vitro, animal and clinical studies which highlight the importance of microbial mechanisms in defining therapeutic responses.

Objective
Aberrant lipid metabolism is a hallmark of colorectal cancer (CRC). Squalene epoxidase (SQLE), a rate-limiting enzyme in cholesterol biosynthesis, is upregulated in CRC. Here, we aim to determine oncogenic function of SQLE and its interplay with gut microbiota in promoting colorectal tumourigenesis.

Design
Paired adjacent normal tissues and CRC from two cohorts were analysed (n=202). Colon-specific Sqle transgenic (Sqle tg) mice were generated by crossing Rosa26-lsl-Sqle mice to Cdx2-Cre mice. Stools were collected for metagenomic and metabolomic analyses.

Results
SQLE messenger RNA and protein expression was upregulated in CRC (p

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 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…

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.

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.

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

Objective
The human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and long-term stability of gut mycobiome among middle-aged and elderly adults. We further explored the interplay between gut fungi and bacteria on metabolic health.

Design
The present study included 1244 participants from the Guangzhou Nutrition and Health Study. We characterised the long-term stability and determinants of the human gut mycobiome, especially long-term habitual dietary consumption. The comprehensive multiomics analyses were performed to investigate the ecological links between gut bacteria, fungi and faecal metabolome. Finally, we examined whether the interaction between gut bacteria and fungi could modulate the metabolic risk.

Results
The gut fungal composition was temporally stable and mainly determined by age, long-term habitual diet and host physiological states. Specifically, compared with middle-aged individuals, Blastobotrys and Agaricomycetes spp were depleted, while Malassezia was enriched in the elderly. Dairy consumption was positively associated with Saccharomyces but inversely associated with Candida. Notably, Saccharomycetales spp interacted with gut bacterial diversity to influence insulin resistance. Bidirectional mediation analyses indicated that bacterial function or faecal histidine might causally mediate an impact of Pichia on blood cholesterol.

Conclusion
We depict the sociodemographic and dietary determinants of human gut mycobiome in middle-aged and elderly individuals, and further reveal that the gut mycobiome may be closely associated with the host metabolic health through regulating gut bacterial functions and metabolites.

Objective
The role of the brain–gut axis is of increasing interest in IBD, as the link between common mental disorders and GI inflammation may be bidirectional. We performed a systematic review examining these issues.

Design
We searched EMBASE Classic and EMBASE, Medline, and APA PsychInfo (to 11 July 2021) for longitudinal follow-up studies examining effect of symptoms of anxiety or depression on subsequent adverse outcomes in IBD, or effect of active IBD on subsequent development of symptoms of anxiety or depression. We pooled relative risks (RRs) and HRs with 95% CIs for adverse outcomes (flare, escalation of therapy, hospitalisation, emergency department attendance, surgery or a composite of any of these) according to presence of symptoms of anxiety or depression at baseline, or RRs and HRs with 95% CIs for new onset of symptoms of anxiety or depression according to presence of active IBD at baseline.

Results
We included 12 separate studies, recruiting 9192 patients. All 12 studies examined brain-to-gut effects. Anxiety at baseline was associated with significantly higher risks of escalation of therapy (RR=1.68; 95% CI 1.18 to 2.40), hospitalisation (RR=1.72; 95% CI 1.01 to 2.95), emergency department attendance (RR=1.30; 95% CI 1.21 to 1.39), or a composite of any adverse outcome. Depression at baseline was associated with higher risks of flare (RR=1.60; 95% CI 1.21 to 2.12), escalation of therapy (RR=1.41; 95% CI 1.08 to 1.84), hospitalisation (RR=1.35; 95% CI 1.17 to 1.57), emergency department attendance (RR=1.38; 95% CI 1.22 to 1.56), surgery (RR=1.63; 95% CI 1.19 to 2.22) or a composite of any of these. Three studies examined gut-to-brain effects. Active disease at baseline was associated with future development of anxiety or depression (RR=2.24; 95% CI 1.25 to 4.01 and RR=1.49; 95% CI 1.11 to 1.98, respectively).

Conclusion
Bidirectional effects of the brain–gut axis are present in IBD and may influence both the natural history of the disease and psychological health.

Circadian timekeeping in intestinal organoids is reset by gut microbe-generated short- chain fatty acids through an epigenetic mechanism of histone deacetylases inhibition.

Gut commensal bacteria modulate synthesis of resolvin D1 in colonic tuft cells. Decreased synthesis of colonic resolvin D1 may contribute to the development of pain in patients with irritable bowel syndrome with diarrhea.