Chemotherapeutic remodeling of the gut microbiome [mouse tissue]

GSE104914 Chemotherapeutic remodeling of the gut microbiome [mouse tissue]: Contributors : P B Chen ; M R Ghadiri

Series Type : Expression profiling by high throughput sequencing

Organism : Mus musculus

The gut microbiome is a dynamic, malleable microbial community that can provoke phenotypic changes in the host that promote or suppress the development of disease. In humans and animals, imbalances in the gut microbiome have been associated with numerous ailments ranging from metabolic disorders such as atherosclerosis to neurological disorders such as autism. Yet, despite considerable promise for advancing a new generation of personalized therapeutics, methods that can achieve selective remodeling of a dysbiotic gut microbiome into a healthy state have not yet been developed. Here we show that a dysfunctional gut microbiome resulting from a high fat diet (HFD) can be remodeled in a targeted manner in vitro and in vivo by using synthetic peptides to treat atherosclerosis. Chemotherapeutic restoration of the gut microbiome following oral administration of the lead peptides caused diverse biological benefits in the host (mouse), including marked reductions in plasma total cholesterol levels and atherosclerotic plaques, increased populations of intestinal Helios+ Treg cells, improved gut integrity, and rebalanced levels of disease-relevant metabolites, such as short-chain fatty acids (SCFAs) and bile acids. Our approach provides a general path to the central goal of treating disease through targeted chemotherapeutic remodeling of the microbiome.