Symbiotic probiotic communities with multiple targets successfully combat obesity in high-fat-diet-fed mice

Area of Science:

• Microbiology
• Metabolic Engineering
• Nutritional Science

Background:

• Metabolic diseases like obesity are complex and multifactorial.
• Probiotic interventions targeting multiple pathways are gaining traction.
• Developing effective multi-strain probiotic combinations requires systematic screening.

Purpose of the Study:

• To screen and identify multi-strain probiotic combinations targeting key obesity-related pathways.
• To evaluate the efficacy and safety of selected symbiotic probiotic communities (SPCs) in preclinical models.
• To elucidate the metabolic interactions within effective SPCs.

Main Methods:

• High-throughput screening of 649 multi-strain combinations against four obesity targets.
• In vitro co-culture and in vivo co-colonization experiments to select SPCs.
• Genome-scale metabolic modeling to analyze microbial interactions.
• Animal studies to assess anti-obesity effects, metabolic improvements, and safety.

Main Results:

• Four (<0.7%) symbiotic probiotic communities (SPCs) were identified from 649 initial combinations.
• SPCs demonstrated lower metabolic resource overlap and enhanced metabolic interactions.
• In vivo studies showed SPCs significantly improved obesity, glucose metabolism, and depression-like behaviors in mice.
• Observed benefits included reduced cholesterol, fat accumulation, and inhibited adipocyte differentiation.

Conclusions:

• Novel multi-strain probiotic combinations (SPCs) can be effectively designed to target complex diseases like obesity.
• SPCs exhibit therapeutic potential by modulating host metabolism and reducing adiposity.
• This approach offers a promising strategy for developing advanced probiotic therapies for obesity and other metabolic disorders.