The novel synbiotic (Lactiplantibacillus plantarum and galacto-oligosaccharides) ameliorates obesity-related metabolic dysfunction: Arginine as a key mediator signaling molecule

This study aimed to develop a novel synbiotic composed of Lactiplantibacillus plantarum LLY-606 and galacto-oligosaccharides (GOS) to improve lipid metabolism in obesity. Design Through genome-wide analysis using COG and CAZy databases, we identified GOS as a specific growth substrate for Lactiplantibacillus plantarum LLY-606. The efficacy of this synbiotic (LP-GOS) was evaluated in both obese individuals and high-fat diet-induced obese mice. LP-GOS supplementation reduced visceral fat and waist circumference in humans and attenuated obesity in mice. It also improved gut microbiota composition and increased serum arginine levels. Metabolomic and microbiota analyses suggested that enhanced arginine production plays a key role. This was further confirmed by arginine synthesis inhibition, antibiotic treatment, and CRISPR-Cas9-mediated knockout of the Ass1 gene in Lactiplantibacillus plantarum LLY-606. These interventions demonstrated that LP-GOS improves lipid metabolism through arginine-mediated activation of the AMPK pathway. LP-GOS effectively alleviates obesity-associated lipid metabolism disorders by enhancing arginine production and activating the AMPK signaling pathway.