The goal of this observational study is to assess the efficacy and safety of the probiotic Escherichia coli Nissle 1917 (EcN®, Ca.Di.Group S.p.A) in the treatment of symptomatic patients after an episode of both complicated and uncomplicated acute colonic diverticulitis.
The main question it aims to answer are:
* Is the studied probiotic able to significantly reduce symptoms, assessed by means of a validated and dedicated score?
* Is there any difference in microbiota among the study group at baseline and a selected cohort of patients subdivided in subjects with diverticulosis and asymptomatic subjects after an episode of acute uncomplicated diverticulitis or an episode of complicated diverticulitis submitted to surgery with colonic resection without stoma?
* Is there any difference in microbiota in the study group at baseline and after 3 and 6 months of treatment with the probiotic?
* Is there any correlation between microbiota modification and symptoms during follow-up?
* Is there any impact on fecal calprotectin values before and during probiotic therapy?
* Is there any modification of evacuation before and during follow-up?
* Is probiotic able to prevent recurrent episodes of acute diverticulitis during follow-up?
* The safety of the probiotic will be assessed during the follow-up. The study group will be assessed at baseline and during follow-up with a dedicated clinical score and Bristol stool scale. Microbiota and fecal calprotectin values will be also assessed at baseline and during follow-up. Microbiota at baseline will be also evaluated for comparison in the three selected groups with diverticulosis and both asymptomatic and symptomatic after an episode of acute diverticulitis.

开始日期2023-05-01

申办/合作机构

Sapienza University of Rome

ChiCTR2200061970 / Suspended临床4期IIT

Clinical study of the colonization efficiency of Mutaflor capsules in the gut of healthy people: a single-center open-ended study

开始日期2022-07-01

申办/合作机构

南方医科大学珠江医院

100 项与 Escherichia coli strain Nissle 1917(Ardeypharm) 相关的临床结果

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100 项与 Escherichia coli strain Nissle 1917(Ardeypharm) 相关的转化医学

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100 项与 Escherichia coli strain Nissle 1917(Ardeypharm) 相关的专利（医药）

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192

项与 Escherichia coli strain Nissle 1917(Ardeypharm) 相关的文献（医药）

2024-11-14·Nature

Probiotic neoantigen delivery vectors for precision cancer immunotherapy

Article

作者: Rouanne, Mathieu ; Redenti, Andrew ; Sun, William ; Jang, YoungUk ; Ballister, Edward R ; Ballister, Edward R. ; Vincent, Rosa L ; Vardoshivilli, Ana ; Gurbatri, Candice R ; Komaranchath, Meghna ; Arpaia, Nicholas ; Sheng, Zeren ; Hahn, Jaeseung ; Redenti, Benjamin ; Danino, Tal ; Im, Jongwon ; Gurbatri, Candice R. ; Huang, Shunyu ; Li, Fangda ; Vincent, Rosa L.

Microbial systems have been synthetically engineered to deploy therapeutic payloads in vivo^1,2. With emerging evidence that bacteria naturally home in on tumours^3,4 and modulate antitumour immunity^5,6, one promising application is the development of bacterial vectors as precision cancer vaccines^2,7. Here we engineered probiotic Escherichia coli Nissle 1917 as an antitumour vaccination platform optimized for enhanced production and cytosolic delivery of neoepitope-containing peptide arrays, with increased susceptibility to blood clearance and phagocytosis. These features enhance both safety and immunogenicity, achieving a system that drives potent and specific T cell-mediated anticancer immunity that effectively controls or eliminates tumour growth and extends survival in advanced murine primary and metastatic solid tumours. We demonstrate that the elicited antitumour immune response involves recruitment and activation of dendritic cells, extensive priming and activation of neoantigen-specific CD4⁺ and CD8⁺ T cells, broader activation of both T and natural killer cells, and a reduction of tumour-infiltrating immunosuppressive myeloid and regulatory T and B cell populations. Taken together, this work leverages the advantages of living medicines to deliver arrays of tumour-specific neoantigen-derived epitopes within the optimal context to induce specific, effective and durable systemic antitumour immunity.

2024-10-23·Applied and Environmental Microbiology

Engineering probiotic Escherichia coli Nissle 1917 to block transfer of multiple antibiotic resistance genes by exploiting a type I CRISPR-Cas system

Article

作者: Sun, Dongchang ; Yang, Hua ; Fei, Mingyue ; Tang, Biao ; Liu, Zhizhi ; Wang, Chenyu ; Zhang, Ruiting ; Fang, Mengdie

ABSTRACT Many multidrug-resistant (MDR) bacteria have evolved through the accumulation of antibiotic resistance genes (ARGs). Although the potential risk of probiotics as reservoirs of ARGs has been recognized, strategies for blocking the transfer of ARGs while using probiotics have rarely been explored. The probiotic Escherichia coli Nissle 1917 (EcN) has long been used for treating intestinal diseases. Here, we demonstrate frequent transfer of ARGs into EcN both in vitro and in vivo , raising concerns about its potential risk of accumulating antibiotic resistance. Given that no CRISPR-Cas system was found in natural EcN, we integrated the type I-E CRISPR-Cas3 system derived from E. coli BW25113 into EcN. The engineered EcN was able to efficiently cleave multiple ARGs [i.e., mcr-1 , blaNDM-1 , and tet (X)] encoding enzymes for degrading last-resort antibiotics. Through co-incubation of EcN expressing Cas3-Cascade and that expressing Cas9, we showed that the growth of the former strain outcompeted the latter strain, demonstrating a better clinical application prospect of EcN expressing the type I-E CRISPR-Cas3 system. In the intestine of a model animal (i.e., zebrafish), the engineered EcN exhibited immunity against the transfer of CRISPR-targeted ARGs. Our work equips EcN with immunity against the transfer of multiple ARGs by exploiting the exogenous type I-E CRISPR-Cas3 system, thereby reducing the risk of the spread of ARGs while using it as a probiotic chassis for generating living therapeutics. IMPORTANCE To reduce the development of antibiotic resistance, probiotics have been considered as a substitute for antibiotics. However, probiotics themselves are reservoirs of antibiotic resistance genes (ARGs). This study introduces a new strategy for limiting the spread of ARGs by engineering the typical probiotic strain Escherichia coli Nissle 1917 (EcN), which has been used for treating intestinal diseases and developed as living therapeutics. We also demonstrate that the type I CRISPR-Cas system imposes a lower growth burden than the type II CRISPR-Cas system, highlighting its promising clinical application potential. Our work not only provides a new strategy for restricting the transfer of ARGs while using probiotics but also enriches the genetic engineering toolbox of EcN, paving the way for the safe use and development of probiotics as living therapeutics.

2024-09-01·Biomaterials

Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery

Article

作者: Liu, Nanhui ; Miao, Yu ; Liu, Yi ; Yang, Yang ; Niu, Le ; Wu, Yumin ; Zhu, Jiafei ; Li, Maoyi ; Bai, Boxiong ; Chen, Qian ; Chen, Linfu

Inflammatory bowel disease (IBD) is a kind of auto-immune disease characterized by disrupted intestinal barrier and mucosal epithelium, imbalanced gut microbiome and deregulated immune responses. Therefore, the restoration of immune equilibrium and gut microbiota could potentially serve as a hopeful approach for treating IBD. Herein, the oral probiotic Escherichia coli Nissle 1917 (ECN) was genetically engineered to express secretable interleukin-2 (IL-2), a kind of immunomodulatory agent, for the treatment of IBD. In our design, probiotic itself has the ability to regulate the gut microenvironment and IL-2 at low dose could selectively promote the generation of regulatory T cells to elicit tolerogenic immune responses. To improve the bioavailability of ECN expressing IL-2 (ECN-IL2) in the gastrointestinal tract, enteric coating Eudragit L100-55 was used to coat ECN-IL2, achieving significantly enhanced accumulation of engineered probiotics in the intestine. More importantly, L100-55 coated ECN-IL2 could effectively activated Treg cells to regulate innate immune responses and gut microbiota, thereby relieve inflammation and repair the colon epithelial barrier in dextran sodium sulfate (DSS) induced IBD. Therefore, genetically and chemically modified probiotics with excellent biocompatibility and efficiency in regulating intestinal microflora and intestinal inflammation show great potential for IBD treatment in the future.

100 项与 Escherichia coli strain Nissle 1917(Ardeypharm) 相关的药物交易

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