Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice

Abstract

Background: Obesity is a major problem worldwide and severely affects public safety. As a metabolite of gut microbiota, endogenous butyric acid participates in energy and material metabolism. Considering the serious side effects and weight regain associated with existing weight loss interventions, novel strategies are urgently needed for prevention and treatment of obesity. Results: In the present study, we engineered Bacillus subtilis SCK6 to exhibited enhanced butyric acid production. Compared to the original Bacillus subtilis SCK6 strain, the genetically modified BsS-RS06550 strain had higher butyric acid production. The mice were randomly divided into four groups: a normal diet (C) group, a high-fat diet (HFD) group, an HFD + Bacillus subtilis SCK6 (HS) group and an HFD + BsS-RS06550 (HE) group. The results showed BsS-RS06550 decreased the body weight, body weight gain, and food intake of HFD mice. BsS-RS06550 had beneficial effects on blood glucose, insulin resistance and hepatic biochemistry. After the 14-week of experiment, fecal samples were collected for nontargeted liquid chromatography-mass spectrometry analysis to identify and quantify significant changes in metabolites. Sixteen potentially significant metabolites were screened, and BsS-RS06550 was shown to potentially regulate disorders in glutathione, methionine, tyrosine, phenylalanine, and purine metabolism and secondary bile acid biosynthesis. Conclusions: In this study, we successfully engineered Bacillus subtilis SCK6 to have enhanced butyric acid production. The results of this work revealed that the genetically modified live bacterium BsS-RS06550 showed potential antiobesity effects, which may have been related to regulating the levels of metabolites associated with obesity. These results indicate that the use of BsS-RS06550 may be a promising strategy to attenuate obesity.

Comparative Fecal Metabolomes of Silkworms Being Fed Mulberry Leaf and Artificial Diet

“…Butanoic acid is generally produced by the metabolism of the bacteria in the intestine [41]. researchers have shown that feeding mice with engineered Bacillus subtilis SCK6, which produces butanoic acid, can cause reduced food intake and weight loss in mice [42]. And we found that the butanoic acid content in AF feces was 13.56 times higher than that of the MF feces.…”

Gut microbiota–derived short-chain fatty acids protect against the progression of endometriosis

“…Our findings that n-butyrate inhibited HDAC activity and that HDAC activity is required for endometriotic cell growth are consistent with studies reporting elevated HDAC1 expression in lesions from women with endometriosis ( 85 , 86 ). Thus, future efforts could be directed at delivering HDAC inhibitors, bacteria engineered to over-produce n-butyrate ( 87 , 88 ), n-butyrate producing Lactobacillus strains ( 81 ), or n-butyrate analogs to treat endometriosis.…”

Engineered Butyrate-producing Bacillus Subtilis Alleviated Ethanol-induced Intestinal and Liver Damage in Mice

“…The Bacillus strains used in the study are shown in Table 1. Wild-type B. subtilis sck6 (BS) and engineered butyrate-producing B. subtilis sck6 (BsS-RS06550, BPBS) was engineered by Dr. Liang Bai (Bai et al 2020). Single colonies of BS and BPBS strains were cultured in LB broth at 37 °C overnight with shaking (200 rpm).…”