A genetic safeguard for eliminating target genes in synthetic probiotics in response to a loss of the permissive signal in a gut environment DOI Creative Commons

Nathalie T. Nguyen,

Miaomiao Wang, Li Li

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

SUMMARY Following the development of therapeutic probiotics, there is an emerging demand for constraining engineered microbial activities to ensure biosafety. Many biocontainment studies developed genetic devices that involve cell death and growth inhibition on microbes, which often create basal levels cytotoxicity hamper fitness performance functions; furthermore, these toxic pathways may promote instability leads mutations breakdown circuit. To address this issue, here we explore a circuit design destroys materials in probiotic strain, instead killing cells, under non-permissive conditions. Our safeguard involves two-layered transcriptional regulatory control expression CRISPR system targets genes degradation. In Escherichia coli Nissle 1917 ( EcN ), continuously scavenged destroyed target until no cellular function could be detected, suggesting strategy has potential avoid escapee formation. Additionally, did not affect fitness. We further demonstrated probiotics inhabited mouse guts continued at least 7 days when permissive signal was supplied constantly; provided, became undetectable within two days. Together, support our feasible synthetic applications. HIGHLIGHTS only does kill host microbes It terminated response loss This allowed inhabit week Cellobiose great serve as continuous

Язык: Английский

Microbiome Integrity Enhances the Efficacy and Safety of Anticancer Drug DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomedicines, Год журнала: 2025, Номер 13(2), С. 422 - 422

Опубликована: Фев. 10, 2025

The intricate relationship between anticancer drugs and the gut microbiome influences cancer treatment outcomes. This review paper focuses on role of integrity in enhancing efficacy safety drug therapy, emphasizing pharmacokinetic interactions microbiota. It explores how disruptions to composition, or dysbiosis, can alter metabolism, immune responses, side effects. By examining mechanisms disruption caused by drugs, this highlights specific case studies like cyclophosphamide, 5-fluorouracil, irinotecan, their impact microbial diversity clinical also discusses microbiome-targeted strategies, including prebiotics, probiotics, postbiotics, fecal microbiota transplantation (FMT), as promising interventions enhance treatment. Furthermore, potential profiling personalizing therapy integrating these into practice is explored. Finally, proposes future research directions, developing novel biomarkers a deeper comprehension drug-microbiome interactions, respond current gaps knowledge improve patient outcomes care.

Язык: Английский

Процитировано

4
Yeast paves the way for cancer immunotherapy DOI
Dingjiacheng Jia, Shujie Chen

Cell chemical biology, Год журнала: 2025, Номер 32(1), С. 9 - 11

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Gut Competition Dynamics of Live Bacterial Therapeutics Are Shaped by Microbiome Complexity, Diet, and Therapeutic Transgenes DOI Creative Commons

Nicole Siguenza,

S. E. R. Bailey,

Mohammad Sadegi

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Competitive exclusion is conventionally believed to prevent the establishment of a secondary strain same bacterial species in gut microbiome, raising concerns for deployment live therapeutics (LBTs), especially if chassis native gut. In this study, we investigated factors influencing competition dynamics murine using isogenic Escherichia coli strains. We found that outcomes are context-dependent, modulated by microbiome complexity, LBT transgene expression, intestinal inflammation, and host diet. Furthermore, demonstrated LBTs can establish long-term engraftment alongside parental strain, with transgene-associated fitness effects competition. identified various interventions, including strategic dosing dietary modulation, significantly enhanced colonization levels 2 3 orders magnitude. These insights provide framework optimizing efficacy, supporting their potential translation human therapeutic applications.

Язык: Английский

Процитировано

0
Advances in developing novel therapeutics, strategies, approaches, and use of emerging techniques DOI
Prasann Kumar

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 291 - 318

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
Advanced microbiome therapeutics for oral delivery of peptides and proteins: Advances, challenges, and opportunities DOI Creative Commons

Hitesh P Gelli,

Ruben Vazquez-Uribe, Stephen T. Buckley

и другие.

Advanced Drug Delivery Reviews, Год журнала: 2025, Номер unknown, С. 115603 - 115603

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Enhancing intestinal absorption of a macromolecule through engineered probiotic yeast in the murine gastrointestinal tract DOI Creative Commons

Hitesh P Gelli,

Karl Alex Hedin, Martin Frederik Laursen

и другие.

Trends in biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Oral administration of therapeutic peptides is limited by poor intestinal absorption. Use engineered microorganisms as drug delivery vehicles can overcome the challenges faced conventional methods. The potential to act synergistically with therapeutics they deliver opens new horizons for noninvasive treatment modalities. This study a probiotic yeast, Saccharomyces boulardii, produce cell-penetrating (CPPs) in situ enhanced permeability. Four CPPs were integrated into yeast chromosome: RRL helix, Shuffle, Penetramax, and PN159. In vitro tests on Caco-2 cell model showed that three CPP-producing strains increased permeability without causing permanent damage. vivo experiments mice revealed Sb PN159 over 10 days significantly FITC-dextran translocation bloodstream inflammation. demonstrates, first time, ability an microorganism modulate host improved absorption macromolecule.

Язык: Английский

Процитировано

2
A genetic safeguard for eliminating target genes in synthetic probiotics in response to a loss of the permissive signal in a gut environment DOI Creative Commons

Nathalie T. Nguyen,

Miaomiao Wang, Li Li

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 16, 2024

SUMMARY Following the development of therapeutic probiotics, there is an emerging demand for constraining engineered microbial activities to ensure biosafety. Many biocontainment studies developed genetic devices that involve cell death and growth inhibition on microbes, which often create basal levels cytotoxicity hamper fitness performance functions; furthermore, these toxic pathways may promote instability leads mutations breakdown circuit. To address this issue, here we explore a circuit design destroys materials in probiotic strain, instead killing cells, under non-permissive conditions. Our safeguard involves two-layered transcriptional regulatory control expression CRISPR system targets genes degradation. In Escherichia coli Nissle 1917 ( EcN ), continuously scavenged destroyed target until no cellular function could be detected, suggesting strategy has potential avoid escapee formation. Additionally, did not affect fitness. We further demonstrated probiotics inhabited mouse guts continued at least 7 days when permissive signal was supplied constantly; provided, became undetectable within two days. Together, support our feasible synthetic applications. HIGHLIGHTS only does kill host microbes It terminated response loss This allowed inhabit week Cellobiose great serve as continuous

Язык: Английский

Процитировано

0