Loading
Life sciences · Journal article
Acs Synthetic Biology · October 27, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Abstract Glucagon-like peptide-1 (GLP-1) receptor agonists and GLP-1 analogs are widely used for type 2 diabetes (T2D) and weight management, but current approaches can be limited by manufacturing complexity, cost, formulation requirements, and the need for repeated administration. Living microbial delivery systems offer a potential strategy for sustained gastrointestinal production of therapeutic peptides, but achieving stable expression, intestinal survival, and biologically relevant systemic exposure remains challenging. Here, we developed an engineered Bacillus subtilis (B. subtilis) spore-based platform for the gastrointestinal delivery of pentameric GLP-1. By leveraging the stress resistance, storage stability, and genetic tractability of B. subtilis, we generated a chromosomally integrated strain that secretes a multimeric GLP-1 construct designed to be processed in the intestine into monomeric GLP-1 peptides. Oral administration of engineered spores resulted in a mean serum GLP-1-related peptide concentration of 20.61 and 23.96 nM on days 3 and 5, respectively, in the first trial and 18.72 and 29.27 nM on days 3 and 7, respectively, in an independent second trial, with minimal detectable signal in green fluorescent protein (GFP) spore-treated controls. Treatment was also associated with preliminary glucose-lowering activity in a fasting-refeeding test. In a longer-term study, engineered spore administration was associated with reduced body weight and adiposity in mice with pre-existing diet-induced obesity, with semaglutide included as a positive pharmacologic benchmark. To improve its translational application, we further generated a marker-free strain that retained probiotic-relevant features of the parental strain, including gastrointestinal stress tolerance, epithelial cell adhesion, and antibiotic susceptibility. These findings provide proof of concept that engineered spore-forming bacteria may serve as a gastrointestinal peptide delivery platform and support further evaluation of this approach in disease-relevant models of metabolic dysfunction.