The substantially increased prevalence of obesity and obesity-related
diseases has generated considerable concern. Currently, synthetic biological strategies
have played an essential role in preventing and treating chronic diseases such as obesity.
A growing number of symbiotic bacteria used as vectors for genetic engineering have
been applied to create living therapeutics. In this study, using Bacillus subtilis as a cellular
chassis, we constructed the engineered butyrate-producing strain BsS-RS06551 with a butyrate yield of 1.5 g/liter. A mouse model of obesity induced by a high-fat diet (HFD) was
established to study the long-term intervention effects of this butyrate-producing bacteria
on obesity. Combined with phenotypic assay results, we found that BsS-RS06551 could
effectively retard body weight gain induced by a high-fat diet and visceral fat accumulation of mice, whereas it could improve glucose tolerance and insulin tolerance, reducing
liver damage. We explored the BsS-RS06551 mechanism of action on host function and
changes in intestinal flora by integrating multiple omics profiling, including untargeted
metabolomics and metagenomics. The results showed that 24 major differential metabolites were involved in the metabolic regulation of BsS-RS06551 to prevent obesity in mice,
including bile acid metabolism, branch chain amino acids, aromatic amino acids, and other
metabolic pathways. Continuous ingestion of BsS-RS06551 could regulate gut microbiota
composition and structure and enhance intestinal flora metabolic function abundance,
which was closely related to host interactions. Our results demonstrated that engineered
butyrate-producing bacteria had potential as an effective strategy to prevent obesity CLICK TO REVIEW