Discovery of a bacterial peptide as a modulator of GLP-1 and metabolic disease.
Sci Rep
; 10(1): 4922, 2020 03 18.
Article
em En
| MEDLINE
| ID: mdl-32188864
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Proteínas de Bactérias
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Peptídeo 1 Semelhante ao Glucagon
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Doenças Metabólicas
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article