Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia Original paper
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Divine Aleru
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Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Microbes
Microbes
Microbes, short for microorganisms, are tiny living organisms that are ubiquitous in the environment, including on and inside the human body. They play a crucial role in human health and disease, functioning within complex ecosystems in various parts of the body, such as the skin, mouth, gut, and respiratory tract. The human microbiome, which is […]
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Divine Aleru
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Researched by:
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Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study explores the potential of Escherichia coli Nissle 1917 (EcN) for both the detection and treatment of colorectal neoplasia, focusing on its ability to selectively colonize adenomas in genetically engineered mice and its use in human colorectal cancer (CRC) patients. The research aimed to evaluate the utility of EcN as a platform for non-invasive cancer detection via stool and urine assays, and for delivering therapeutic payloads to treat colorectal tumors. The study employs both pre-clinical murine models and clinical trial data to assess EcN’s ability to colonize tumors, produce screening molecules like salicylate, and deliver immunotherapeutic agents directly to neoplastic sites.
Who was studied?
The study involved a combination of genetically engineered mice, including ApcMin/+ mice (a model for familial adenomatous polyposis) and orthotopic models of CRC, to examine tumor colonization and therapeutic efficacy of EcN. In addition, clinical data from colorectal cancer patients were gathered in a prospective, double-blind clinical trial, where patients took either EcN or a placebo for two weeks before undergoing surgical resection of neoplastic and adjacent normal tissue. The study then compared microbial enrichment in tumor samples from the EcN-treated group.
Most important findings
EcN demonstrated selective colonization of colorectal adenomas in genetically engineered and orthotopic mouse models, with strong enrichment in tumor tissues over normal adjacent tissues. The engineered EcN strains, including those producing salicylate for detection and cytokines for therapy, showed potential for non-invasive tracking of adenomas through stool and urine assays. Additionally, EcN engineered to produce immune-modulating therapies (such as GM-CSF and checkpoint inhibitors) significantly reduced adenoma burden by ~50% in the murine models.
Key implications
This study highlights the emerging role of engineered probiotics, like EcN, in the detection and treatment of colorectal cancer. EcN’s ability to selectively target and colonize neoplastic tissue provides a novel method for early detection and non-invasive monitoring of CRC. The successful reduction of adenoma burden through engineered EcN supports its therapeutic potential, particularly for treating CRC subtypes traditionally unresponsive to immunotherapy. This approach could revolutionize CRC treatment by combining diagnostic and therapeutic capabilities in a single oral delivery platform, reducing the need for invasive procedures like colonoscopy.