Risultati per: Microbiota e steatosi epatica: quali evidenze?

Con anticipo di 5 anni, studio Università Bari con Airc

Objective
Faecal microbiota transplantation (FMT) has variable efficacy in treating UC. Recently, oral lyophilised FMT was found to induce remission in patients with UC, with one donor having 100% efficacy compared with a second donor (36% efficacy). We characterised differences in the gut microbiota of these two donors with the aim of improving FMT donor selection.

Design
Faecal samples from the two donors were collected over a period of 44 (donor 1) or 70 (donor 2) weeks. The microbiome and metabolome were profiled using shotgun metagenomics and untargeted metabolomics

Results
Gut microbiome long-term stability was highly evident in the effective donor. Donor microbiota species evenness was a robust feature associated with clinical efficacy across two clinical trials of FMT in UC, leading to increased donor species engraftment in patients. Alpha diversity and beta diversity of donor gut microbiotas significantly differed. 90 bacterial species and one archaeon were differentially abundant between donors, 44 of which were >0.1% in relative abundance. 17/44 species were enriched in the effective donor, 11 of which (64.7%) were assembled into high-quality genomes that were prevalent (≥75% samples) in that donor, and six showed evidence of engraftment in patients. Taxonomic differences between donors translated to substantial microbial functional differences that were validated using metabolomics.

Conclusion
Donor microbiota stability and species evenness were identified as novel metrics that were associated with therapeutic efficacy in UC, beyond individual microbial species or metabolites. These metrics may represent community resilience that translates to better engraftment in the host.

Trial registration number
ACTRN12619000611123.

After becoming an established therapy for recurrent Clostridioides difficile infection (rCDI), faecal microbiota transplantation (FMT) has been investigated also in non-communicable disorders, including IBD, IBS, metabolic syndrome, neurological disease and others.1 While the transfer of a healthy biomass appears to be effective regardless of its composition in rCDI (which is an example of acute, elementary dysbiosis), increasing evidence suggests that the clinical success of FMT in chronic disorders is influenced by several factors, including donor microbiome composition2 or FMT working protocols,3 and that these effects may be mediated by the engraftment capacity of the donor microbiome into the recipient gut.4 Haifer et al5 have published in the latest issue of Gut a subanalysis of a recent randomised trial (the LOTUS trial) of FMT for UC,6 where they had observed a significant variability of clinical efficacy between the…

Accumulating evidence indicates that gut transit time is a key factor in shaping the gut microbiota composition and activity, which are linked to human health. Both population-wide and small-scale studies have identified transit time as a top covariate contributing to the large interindividual variation in the faecal microbiota composition. Despite this, transit time is still rarely being considered in the field of the human gut microbiome. Here, we review the latest research describing how and why whole gut and segmental transit times vary substantially between and within individuals, and how variations in gut transit time impact the gut microbiota composition, diversity and metabolism. Furthermore, we discuss the mechanisms by which the gut microbiota may causally affect gut motility. We argue that by taking into account the interindividual and intraindividual differences in gut transit time, we can advance our understanding of diet–microbiota interactions and disease-related microbiome signatures, since these may often be confounded by transient or persistent alterations in transit time. Altogether, a better understanding of the complex, bidirectional interactions between the gut microbiota and transit time is required to better understand gut microbiome variations in health and disease.

Objective
Cigarette smoking is a major risk factor for colorectal cancer (CRC). We aimed to investigate whether cigarette smoke promotes CRC by altering the gut microbiota and related metabolites.

Design
Azoxymethane-treated C57BL/6 mice were exposed to cigarette smoke or clean air 2 hours per day for 28 weeks. Shotgun metagenomic sequencing and liquid chromatography mass spectrometry were parallelly performed on mice stools to investigate alterations in microbiota and metabolites. Germ-free mice were transplanted with stools from smoke-exposed and smoke-free control mice.

Results
Mice exposed to cigarette smoke had significantly increased tumour incidence and cellular proliferation compared with smoke-free control mice. Gut microbial dysbiosis was observed in smoke-exposed mice with significant differential abundance of bacterial species including the enrichment of Eggerthella lenta and depletion of Parabacteroides distasonis and Lactobacillus spp. Metabolomic analysis showed increased bile acid metabolites, especially taurodeoxycholic acid (TDCA) in the colon of smoke-exposed mice. We found that E. lenta had the most positive correlation with TDCA in smoke-exposed mice. Moreover, smoke-exposed mice manifested enhanced oncogenic MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated protein kinase 1/2) signalling (a downstream target of TDCA) and impaired gut barrier function. Furthermore, germ-free mice transplanted with stools from smoke-exposed mice (GF-AOMS) had increased colonocyte proliferation. Similarly, GF-AOMS showed increased abundances of gut E. lenta and TDCA, activated MAPK/ERK pathway and impaired gut barrier in colonic epithelium.

Conclusion
The gut microbiota dysbiosis induced by cigarette smoke plays a protumourigenic role in CRC. The smoke-induced gut microbiota dysbiosis altered gut metabolites and impaired gut barrier function, which could activate oncogenic MAPK/ERK signalling in colonic epithelium.

Objective
Microbiome and dietary manipulation therapies are being explored for treating ulcerative colitis (UC). We aimed to examine the efficacy of multidonor faecal microbiota transplantation (FMT) and anti-inflammatory diet in inducing remission followed by long-term maintenance with anti-inflammatory diet in patients with mild-moderate UC.

Design
This open-labelled randomised controlled trial (RCT) randomised patients with mild-moderate (Simple Clinical Colitis Activity Index (SCCAI) 3–9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity (UCEIS) >1) on stable baseline medications in 1:1 ratio to FMT and anti-inflammatory diet (FMT-AID) versus optimised standard medical therapy (SMT). The FMT-AID arm received seven weekly colonoscopic infusions of freshly prepared FMT from multiple rural donors(weeks 0–6) with anti-inflammatory diet. Baseline medications were optimised in the SMT arm. Clinical responders (decline in SCCAI >3) at 8 weeks in both arms were followed until 48 weeks on baseline medications (with anti-inflammatory diet in the FMT-AID arm). Primary outcome measures were clinical response and deep remission (clinical—SCCAI

Circulation, Volume 146, Issue Suppl_1, Page A12300-A12300, November 8, 2022. Introduction:Phenylacetylglutamine (PAGln) has been recently discovered as a gut-microbiota-related metabolite, and circulating PAGln may be related to risks of cardiometabolic abnormalities. Gut microbiota-related dietary intakes and high-protein foods may affect circulating PAGln levels.Hypothesis:We assessed whether circulating PAGln levels may be related to intakes of gut-microbiota-related food intakes, and higher levels of PAGln may be associated with greater degrees of cardiometabolic abnormalities. We also tested a hypothesis that higher levels of circulating PAGln may be related to higher risk of the incident coronary heart disease (CHD).Methods:Circulating levels of PAGln, diet assessed using 7-day dietary records, and cardiometabolic abnormalities were assessed in the Women’s Lifestyle Validation Study (WLVS) (n=723). The associations between plasma PAGln levels and risk of incident CHD were analyzed in a prospective nested case-control of 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses’ Health Study (NHS). We identified incident cases of CHD over 10-14 years of follow-up time.Results:Higher levels of PAGln were associated with higher levels of circulating insulin, triglycerides, as well as lower levels of HDL cholesterol. We found that greater intakes of red meat and processed meat (p=0.01), but not of poultry or fish (p >0.05), and lower intakes of vegetables (p=0.03) were significant factors associated with higher levels of circulating PAGln. In the prospective nested case-control study setting, higher levels of PAGln were associated with higher risk of the incident CHD. Every 1 unit increment of log-transformed PAGln was associated with a relative risk of 1.21 (95% CI: 1.01, 1.45) for the incident CHD.Conclusions:Gut-microbiota-affecting diet quality were related to circulating levels of PAGln. Circulating PAGln levels may be associated with cardiometabolic abnormalities and risk of incident CHD among women.

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.

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 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 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.