Probiotic human alcohol dehydrogenase-4 expressing bacteria protects from diet-induced obesity and metabolic impairment: a new concept of disease prevention

Abstract

Aim: Probiotic bacteria consumption for improving human health and for disease prevention is still controversial. There is a need to develop functional probiotic bacteria with proven efficacy for the human gastrointestinal (GI) system. The novel bacteria will lower the steady state of constant Ethanol production may lead to gut microbiota dysbiosis and liver injuries. Methods: Herein engineered probiotic bacterium B. subtilis to enhance the secretion of human alcohol dehydrogenase-4 (ADH4) by fusion of signal peptides (SPs) was constructed. As a result, higher ADH4 secretion and Ethanol removal rates were observed in phoB SP transformant SP-64, compared to other transformants. The engineered ADH4 expressing probiotic B. subtilis was delivered as spores to evaluate various physiological, biochemical, and immuno-histochemical parameters of mice under a high-fat diet (HFD)-induced obesity and metabolic impairment. Results: The treatment ameliorated significantly weight gain, improved glucose utilization, and prevented HFD-induced pancreatic damage. Lastly, SP-64 inoculation altered the gut microbiota, and increased the Firmicutes/Bacteroides ratio, supporting better fitness under HFD. Conclusions: SP-64 emerged as a potential probiotic that opens a new avenue for interventions against over-nutrition-induced metabolic disorders.