Funded in part by Novo Nordisk, Novo Nordisk Fonden, Novo Nordisk Foundation Center for Basic Metabolic Research
Cold Exposure and Oral Delivery of GLP-1R Agonists by an Engineered Probiotic Yeast Strain Have Antiobesity Effects in Mice
Hedin KA, Zhang H, Kruse V, Rees VE, Bäckhed F, Greiner TU, Vazquez-Uribe R, Sommer MOA
ACS synthetic biology · 36 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Industry funded
- Government
- Västra Götalandsregionen
- Government
- European Commission
- Company
- Novo Nordisk
- University or hospital
- Danmarks Tekniske Universitet
- University or hospital
- Sahlgrenska Universitetssjukhuset
- University or hospital
- Göteborgs Universitet
- Company
- Novo Nordisk Fonden
- Company
- Novo Nordisk Foundation Center for Basic Metabolic Research
- University or hospital
- Sahlgrenska Akademin
- Government
- H2020 Marie Skłodowska-Curie Actions
- Government
- H2020 Marie Sklodowska-Curie Actions
- Nonprofit
- NNF Center for Biosustainability
- Grants
- Novo Nordisk Foundation Center for Basic Metabolic Research (NNF20CC0035580); Danmarks Tekniske Universitet (NNF20CC0035580); H2020 Marie Skłodowska-Curie Actions (813781); Novo Nordisk Fonden (NNF17CO0028232); European Commission (813781); European Commission (NNF20CC0035580); European Commission (HORIZON2020); Novo Nordisk Fonden (813781); Novo Nordisk Fonden (NNF20CC0035580); Novo Nordisk (NNF20CC0035580); Novo Nordisk Fonden (NNF10CC1016517); Novo Nordisk (NNF17CO0028232)
Based on 12 listed funder(s).
Publication
- Published
- 2023-10-12 · ACS Synth Biol · vol. 12 · issue 11 · pp. 3433–3442
- Publisher
- American Chemical Society
- Cited
- 44 citations · more than 98% of similar papers · 6.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 64 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Diabetes Treatment and Management · Pancreatic function and diabetes · Microbial Metabolites in Food Biotechnology
- Keywords
- Probiotic, Saccharomyces boulardii, In vivo, Yeast, Biology, Genetically engineered, Ex vivo, Pharmacology, Medicine, Microbiology, Biotechnology, Bacteria, Biochemistry
- MeSH
- animals, mice, inbred c57bl, humans, mice, saccharomyces cerevisiae, diabetes mellitus, type 2, obesity, peptides, probiotics, male, exenatide
8 authors
From DK, SE
- Karl Alex HedinNovo Nordisk Foundation; Technical University of Denmark
- Hongbin ZhangNovo Nordisk Foundation; Technical University of Denmark
- Vibeke KruseNovo Nordisk Foundation; Technical University of Denmark
- Vanessa Emily ReesNovo Nordisk Foundation; Technical University of Denmark
- Fredrik BäckhedUniversity of Copenhagen; Sahlgrenska University Hospital; Novo Nordisk Foundation; Region Västra Götaland; University of Gothenburg
- Thomas Uwe GreinerUniversity of Gothenburg
Abstract
Advanced microbiome therapeutics (AMTs) holds promise in utilizing engineered microbes such as bacteria or yeasts for innovative therapeutic applications, including the in situ delivery of therapeutic peptides. Glucagon-like peptide-1 receptor agonists, such as Exendin-4, have emerged as potential treatments for type 2 diabetes and obesity. However, current administration methods face challenges with patient adherence and low oral bioavailability. To address these limitations, researchers are exploring improved oral delivery methods for Exendin-4, including utilizing AMTs. This study engineered the probiotic yeast Saccharomyces boulardii to produce Exendin-4 (Sb-Exe4) in the gastrointestinal tract of male C57BL/6 mice to combat diet-induced obesity. The biological efficiency of Exendin-4 secreted by S. boulardii was analyzed ex vivo on isolated pancreatic islets, demonstrating induced insulin secretion. The in vivo characterization of Sb-Exe4 revealed that when combined with cold exposure (8 °C), the Sb-Exe4 yeast strain successfully suppressed appetite by 25% and promoted a 4-fold higher weight loss. This proof of concept highlights the potential of AMTs to genetically modify S. boulardii for delivering active therapeutic peptides in a precise and targeted manner. Although challenges in efficacy and regulatory approval persist, AMTs may provide a transformative platform for personalized medicine. Further research in AMTs, particularly focusing on probiotic yeasts such as S. boulardii, holds great potential for novel therapeutic possibilities and enhancing treatment outcomes in diverse metabolic disorders.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
Community trust
Loading…
How much do you trust this study's findings?
Comments
Sign in to rate, comment on or flag this study.Sign inSomething wrong here?
Flag this study if its information, labels or funding look wrong. An editor reviews every flag.
Sign in to rate, comment on or flag this study.Sign inEducational information about published research. Not medical advice, and not a recommendation to start or stop anything.