Phocaeicola vulgatus alleviates obesity through cross-species arginine production and hepatic retinoic acid signaling

Phocaeicola vulgatus -centered network and ornithine synthesis are impaired in obese individuals. • P. vulgatus alleviates HFD-induced obesity in humanized rats. • P. vulgatus shows a potential functional association with Phascolarctobacterium faecium in enhancing arginine biosynthesis. • Elevated systemic arginine is associated with activated host hepatic retinoic acid signaling. • The arginine-retinoic acid axis highlights P. vulgatus as a probiotic target. Fecal microbiota transplantation (FMT) shows inconsistent clinical efficacy in treating obesity, and the specific microbial determinants dictating its success remain poorly characterized. Our previous clinical FMT trial identified Phocaeicola vulgatus as a key microbe contributing to the therapeutic efficacy of obesity treatment. Here, to investigate its role in obesity, we established an independent clinical cohort comprising obese and lean individuals, revealing that the P. vulgatus -centered network and ornithine synthesis are impaired in the obese group. We then confirmed causality by utilizing a humanized rat model carrying microbiota from a P. vulgatus -deficient obese patient, demonstrating that P. vulgatus supplementation significantly mitigates HFD-induced obesity, including reductions in body weight and serum total cholesterol levels, as well as the alleviation of hepatic steatosis. To further explore the functional mechanisms of P. vulgatus , integrated metagenomic and metabolomic analyses revealed a potential functional association between P. vulgatus and Phascolarctobacterium faecium that is associated with enhanced intestinal arginine biosynthesis and systemic availability. Furthermore, hepatic transcriptomics linked these elevated circulating arginine levels to the upregulation of retinoic acid (RA) signaling. Taken together, our findings outline a potential microbial-host network wherein P. vulgatus mitigates obesity via the arginine-RA axis, providing a valuable scientific basis for exploring this strain as a probiotic candidate for metabolic health. Download: Download high-res image (165KB) Download: Download full-size image