The Gut Microbiota Remodes Amino Acid and Lipid Metabolism in Incomplete Revascularization of CHD with Phlegm-Dampness Syndrome: An Integrated Multiomics and Network Pharmacology Study

Xinyu Zhang¹Wei Jiang^2,3Xiaoqing Li³Wenjing Xu³Tong Liu³Haiming Cao¹Haining Zhao¹Wenhua Shi¹Taohua Lan^2,3*Weihui Lu^2,4,5*

• ¹The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, China
• ²State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
• ³Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China
• ⁴Chinese Medicine Guangdong Laboratory, Guangdong Hengqin, China
• ⁵State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China

Background: Incomplete revascularization of coronary heart disease (IR-CHD) is a novel category of CHD that has developed; such patients often have persistent angina of unknown etiology, which seriously affects quality of life and prognosis and urgently needs in-depth study. Methods: Taking IR-CHD patients with PD Syndrome, non-PD (NPD) Syndrome, and healthy individuals as research subjects, through the integration of microbiomics and metabolomics studies of clinical samples and the network pharmacology research strategy of three classic TCM formulae, we systematically explored the biological basis of TCM Syndrome differentiation for PD Syndromes of IR-CHD. Results: IR-CHD patients with PD Syndrome demonstrated a unique metabolic profile and gut microbiota structure characterized by an increase in branched-chain amino acid metabolism and a decrease in glycerophospholipid metabolism, and 6 Syndrome-specific differential metabolites (DMs) were identified. Additionally, combined analysis of the gut microbiota and metabolites revealed that differential gut microbiota (DGMs), including Muribaculum, Odoribacter, and Agathobacter, may be involved in metabolic disorders associated with amino acids and lipids in PD syndrome. Agathobacter, Odoribacter and 3-methyl-2-oxo-pentanoic acid might be potential biomarkers for PD Syndrome by ROC diagnostic analysis. Furthermore, a comprehensive network pharmacology and multiomics analysis suggested that PD Syndrome formulae regulation overlaps with the metabolic disorder pathway mediated by the gut microbiota in PD syndromes, that is, the PD Syndrome formula may regulate the intestinal microenvironment and improve metabolic disorders through the PD Syndrome-specific pathway in IR-CHD patients. Conclusion: IR-CHD patients with PD TCM Syndrome have amino acid and lipid metabolic disorders and that the gut microbiota plays an important role in their metabolic regulation. This study also provides an evidence-based strategy for exploring the biological basis of TCM Syndrome differentiation, which is helpful for the translation of TCM theory into precision medicine practice.