Lipid stress evolved, microbiome-based probiotics reduce lipid uptake in mice.

Published: 04/22/2026

Authors: Acharya AP, Borrelli MA, Jurczak MJ, Krakoff J, Little SR

Abstract

Controlling the molecular transport of nutrients through the gut is an attractive strategy to modulate host metabolism. Herein, a technique of stress-based evolution of an individual's own microbiota to enhance lipid metabolism is presented, which is based on sequential culture of these bacteria in higher concentrations of lipids. Using this technique, a probiotic formulation of bacterial colonies that exhibit increased lipid metabolism was generated from oral microbiota samples from mice, canine, and human sources. Mice fed a high-fat diet (HFD) and administered lipid stress evolved (LSE) probiotics excreted increased lipids in stool and reduced triglyceride transport into the blood by three-fold till 3 h post-oral gavage of soybean oil, as compared to controls. In addition, these enhanced probiotics prevented weight gain in mice fed a HFD five-fold better than controls and induced weight loss in mice with diet change three-fold faster than diet change alone. In these mice, there was a marked change in appearance with a more healthy, less oily coat. Controlled metabolic cage experiments demonstrated that the total movement, food intake, and water intake were not significantly different between mice receiving LSE probiotic versus a control probiotic formulation, suggesting that important health measures are unchanged with LSE probiotic administration. Overall, this facile stress-based culture technique can be utilized to modulate bacterial metabolism and applied to different industrial processes of probiotic generation and to affect different disease outcomes such as obesity.

PMID: 42016853