Risultati per: Microbiota intestinale e cancro al pancreas

Introduction
The enteric microbiota drives inflammation in Crohn’s disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn’s disease. The Microbial Restoration (MIRO) study aims to establish this evidence.

Methods and analysis
At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn’s Disease Activity Index (CDAI) reduction ≥100 points or to

Nursing Up, per operatori salute rischio tumori del 10% in più

Nursing Up, per operatori salute rischio tumori del 10% in più

Objective
Live biotherapeutic products (LBPs) are biological products composed of living micro-organisms, developed to prevent, treat, or cure diseases. Examples include cultured strains of Akkermansia muciniphila and Christensenella minuta, as well as treatments using purified Firmicutes spores for recurrent Clostridioides difficile infections. There is a need for guidelines over the increasing interest in developing LBPs. A panel of microbiome experts from Asia-Pacific countries articulates their perspectives on key considerations for LBP development.

Design
Experts in microbiome research, microbiology, gastroenterology, internal medicine and biotherapeutics industry were invited to form a panel. During the 2023 Inauguration Conference of the Asia-Pacific Microbiota Consortium, an organised, iterative roundtable discussion was conducted to build expert consensus on critical issues surrounding the development of LBP.

Results
The consensus statements were organised into three main aspects: (a) rationales of LBP development, (b) preclinical studies and (c) preparation for clinical studies. The panel strongly recommended to prioritise human-derived and food-sourced strains for development, with indications based on clinical need and efficacy shown in studies. Preclinical evaluation should involve thorough screening, genotyping and phenotyping, as well as comprehensive in vitro and animal studies to assess functional mechanisms and microbiological safety. Rigorous cell banking practices and genetic monitoring are essential to ensure product consistency and safety throughout the manufacturing process. Clinical trials, including postmarketing surveillance, must be carefully designed and closely monitored, with robust safety and risk management protocols in place.

Conclusions
The development of LBP should be approached with a strong emphasis on microbiological evaluation, clinical relevance, scientific mechanisms and safety at every stage. These measures are essential to ensure the safety, effectiveness and long-term success of the product.

Background
Non-absorbed dietary emulsifiers, including carboxymethylcellulose (CMC), directly disturb intestinal microbiota, thereby promoting chronic intestinal inflammation in mice. A randomised controlled-feeding study (Functional Research on Emulsifiers in Humans, FRESH) found that CMC also detrimentally impacts intestinal microbiota in some, but not all, healthy individuals.

Objectives
This study aimed to establish an approach for predicting an individual’s sensitivity to dietary emulsifiers via their baseline microbiota.

Design
We evaluated the ability of an in vitro microbiota model (MiniBioReactor Arrray, MBRA) to reproduce and predict an individual donor’s sensitivity to emulsifiers. Metagenomes were analysed to identify signatures of emulsifier sensitivity.

Results
Exposure of human microbiotas, maintained in the MBRA, to CMC recapitulated the differential CMC sensitivity previously observed in FRESH subjects. Furthermore, select FRESH control subjects (ie, not fed CMC) had microbiotas that were highly perturbed by CMC exposure in the MBRA model. CMC-induced microbiota perturbability was associated with a baseline metagenomic signature, suggesting the possibility of using one’s metagenome to predict sensitivity to dietary emulsifiers. Transplant of human microbiotas that the MBRA model deemed CMC-sensitive, but not those deemed insensitive, into IL-10–/– germfree mice resulted in overt colitis following CMC feeding.

Conclusion
These results suggest that an individual’s sensitivity to emulsifier is a consequence of, and can thus be predicted by, examining their baseline microbiota, paving the way to microbiota-based personalised nutrition.

PaperClipThe adult pancreas protects against cancer by actively expelling genetically mutated cells. Pancreatic cancer starts with cells carrying KRAS mutations; however, it is not clear how some KRAS mutant cells override cell elimination mechanisms to survive in tissues.MethodsWe used an in vivo mouse model of sporadic tumorigenesis to induce Kras and/or Tp53 mutations in low numbers of cells in the adult pancreas. We monitored mutant cell fate over time using quantitative fluorescence imaging.

The gut microbiome is involved in human health and disease, and its comprehensive understanding is necessary to exploit it as a diagnostic or therapeutic tool. Multi-omics approaches, including metagenomics, metatranscriptomics, metabolomics, and metaproteomics, enable depicting the complexity of the gut microbial ecosystem. However, these tools generate a large data stream, which integration is needed to produce clinically useful readouts but, in turn, might be difficult to carry out with conventional statistical methods.

Introduction
Acute-on-chronic liver failure (ACLF) patients have the highest propensity for post-liver transplantation (LT) infections and mortality. Liver-associated diseases have been one of the primary targets for synbiotic therapy to augment immunity and mitigate infections. However, despite multiple studies showing benefits of synbiotics in liver diseases, data on their use following LT are sparse.

Methods and analysis
This randomised placebo-controlled study aims to assess the impact of synbiotics in ACLF patients undergoing living donor liver transplantation (LDLT). Following randomisation by computer-generated block number sequence, 3 days prior to LDLT, the intervention arm will receive standard medical treatment and synbiotics (VSL#3 a probiotic, and Yogut, prebiotic and probiotic combination) for 6 weeks, while the control arm will receive standard medical treatment with a placebo. The patients will be followed up for 6 months to study the clinical and biochemical outcomes. The primary objective is to compare the difference in the occurrence of infectious complications between the patients who receive synbiotics versus placebo during the 6-month period following LDLT. The secondary objectives include assessing the qualitative and quantitative change in microbiota with synbiotics and LDLT, adverse reactions due to synbiotics, and post-LT morbidity and mortality. The minimum sample size comes to 71 in each group. The first 50 patients in the study protocol will undergo gut microbiome analysis using 16s metagenomic and nanopore sequencing to analyse the microbial composition before starting synbiotics/placebo and at 6 weeks after LDLT.

Ethics and dissemination
The study is approved by the Research Ethics Committee of Amrita Institute of Medical Sciences, Kochi, India (IEC-AIMS-2022-GISUR-203) and registered in the Clinical Trial Registry of India (CTRI) CTRI/2022/10/046327. The results of the trial will be disseminated by presentation at national/international conferences and publication in peer-reviewed journals.

Trial registration number
CTRI/2022/10/046327 – Clinical Trial Registry of India

Studio, una bevanda al giorno aumenta il rischio di 5 volte

Studio, una bevanda al giorno aumenta il rischio di 5 volte

We have read with interest the contribution by Bedke et al,1 reporting changes in the stool microbiota associated with primary sclerosing cholangitis (PSC) in human and murine models of the disease. These changes coincide with an expansion of FoxP3+T reg cells, a response also linked with luminal butyrate concentrations and/or other goods and services arising from select commensal bacteria.2 Furthermore, the authors find patients with PSC with an associated IBD (PSC-IBD) as well as mice receiving faecal transfer from such patients experience a milder form of IBD, or attenuation of colitis, respectively. Their findings expand on those from Awoniyi et al, linking bile acid ecology and select stool bacteria deemed protective or pathogenic in a murine model of PSC, as well as an association of these microbial signatures with disease severity in patients with PSC.3 Attribution of the beneficial effects to the luminal/stool…