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

et al.

Trends in biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

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

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 422 - 422

Published: Feb. 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.

Language: Английский

Citations

3
Yeast paves the way for cancer immunotherapy DOI
Dingjiacheng Jia, Shujie Chen

Cell chemical biology, Journal Year: 2025, Volume and Issue: 32(1), P. 9 - 11

Published: Jan. 1, 2025

Language: Английский

Citations

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

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

Citations

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

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 291 - 318

Published: Jan. 1, 2025

Language: Английский

Citations

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

Hitesh P. Gelli,

Ruben Vazquez-Uribe, Stephen T. Buckley

et al.

Advanced Drug Delivery Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 115603 - 115603

Published: May 1, 2025

Language: Английский

Citations

0
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

Nhu T. Nguyen,

Miaomiao Wang, Li Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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

Language: Английский

Citations

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

et al.

Trends in biotechnology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 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.

Language: Английский

Citations

0