Language
English
Publication Date
3-18-2020
Journal
Scientific Reports
DOI
10.1038/s41598-020-61112-0
PMID
32188864
PMCID
PMC7080827
PubMedCentral® Posted Date
5-18-2020
PubMedCentral® Full Text Version
Post-print
Abstract
Early work in rodents highlighted the gut microbiota's importance in metabolic disease, including Type II Diabetes Mellitus (T2DM) and obesity. Glucagon-like peptide-1 (GLP-1), an incretin secreted by L-cells lining the gastrointestinal epithelium, has important functions: promoting insulin secretion, insulin sensitivity, and β-cell mass, while inhibiting gastric emptying and appetite. We set out to identify microbial strains with GLP-1 stimulatory activity as potential metabolic disease therapeutics. Over 1500 human-derived strains were isolated from healthy individuals and screened for GLP-1 modulation by incubating bacterial cell-free supernatants with NCI H716 L-cells. Approximately 45 strains capable of increasing GLP-1 were discovered. All GLP-1 positive strains were identified as Staphylococcus epidermidis by 16S rRNA sequencing. Mass spectrometry analysis identified a 3 kDa peptide, Hld (delta-toxin), present in GLP-1 positive supernatants but absent in GLP-1 neutral supernatants. Studies in NCI-H716 cells and human jejunal enteroids engineered to make more enteroendocrine cells demonstrated that Hld alone is sufficient to enhance GLP-1 secretion. When administered in high-fat-fed mice, Hld-producing S. epidermidis significantly reduced markers associated with obesity and T2DM. Further characterization of Hld suggests GLP-1 stimulatory action of Hld occurs via calcium signaling. The presented results identify a novel host-microbe interaction which may ultimately lead to the development of a microbial peptide-based therapeutic for metabolic disease.
Keywords
Animals, Bacterial Proteins, Biomarkers, Calcium, Calcium Signaling, Cell Line, Dose-Response Relationship, Drug, Female, Glucagon-Like Peptide 1, Humans, Intracellular Space, Metabolic Diseases, Mice, Peptides, Microbiology, Metabolism
Published Open-Access
yes
Recommended Citation
Tomaro-Duchesneau, Catherine; LeValley, Stephanie L; Roeth, Daniel; et al., "Discovery of a Bacterial Peptide as a Modulator of GLP-1 and Metabolic Disease" (2020). Faculty and Staff Publications. 671.
https://digitalcommons.library.tmc.edu/baylor_docs/671
Included in
Biochemical Phenomena, Metabolism, and Nutrition Commons, Biochemistry, Biophysics, and Structural Biology Commons, Biology Commons, Integrative Medicine Commons, Medical Microbiology Commons