(P19-024-25) The Role of Gut Microbiota and Arginine Metabolism in Blood Lipid Regulation During Low-Carb Diet Intervention

Objectives: Our prior study in overweight Chinese women showed that both low-carbohydrate (LC) and energy-restricted (ER) diets promoted weight loss, with LC diet particularly improving dyslipidemia. We aimed to explore the role of gut microbiota and its interactions with host in regulating blood lipid metabolism under LC dietary intervention. 

Methods: Fecal and blood samples from 48 participants were collected at baseline and after a 12-week dietary intervention in the ER and LC diet groups. Metagenome sequencing carried on Illumina HiSeq X Ten and targeted metabolomic profiling using the Q300 kit (Metabo-Profile, Shanghai, China) quantified the gut microbiota and its associated metabolites. The mouse experiments with arginine supplementation and low carbohydrate dietary intervention, along with antibiotics were conducted, followed by shotgun metagenomic sequencing.

Results: Compared to ER group (n=25), the blood lipid profiles of LC group (n=25) were significantly improved. The plasma metabolome and gut metagenome profiling were  significantly altered in LC group (metabolome PERMANOVA P < 0.001, metagenome PERMANOVA P < 0.001). Moreover, the differential plasma metabolites were predominantly amino acid-related with 15 amino acids altered greatly, particularly those in the ornithine cycle pathway. Furthermore, the significantly change of arginine levels was linked to downregulation of arginine synthetase (argH) in Bacteroides stercoris and upregulation of arginine catabolic enzyme (rocF) in Prevotella copri in the LC diet. In mice experiments, both low carbohydrate dietary intervention and arginine supplementation reduced serum total cholesterol and low-density lipoprotein cholesterol levels. Nevertheless, these effects were diminished after the depletion of gut microbiota, indicating microbiota-mediated lipid improvements.

Conclusions: Through an integrative multi-omics approach and mouse models, we elucidated the mechanisms underlying the low-carbohydrate dietary pattern's beneficial effects on blood lipid profiles via gut microbiota's role in arginine metabolism. This highlights the microbiota's importance in dietary intervention and host metabolic regulation.

Funding Sources: We thank the Human Phenome Data Center for data support and acknowledge funding from the Shang Municipal Science and Technology Major Project.