Multi-Omics Insights into Microbiome and Metabolite Signatures as Potential Biomarkers for Feline Hypertrophic Cardiomyopathy

Gut microbial dysbiosis and metabolites are associated with cardiovascular disease. Hypertrophic cardiomyopathy (HCM) is one of the most common feline cardiovascular diseases and can be a model for human HCM. Through multi-omics analysis, integrated analysis of the gut microbiome, metabolome, and disease can be performed to identify potential mechanistic links, diagnostic biomarkers, and potential therapeutic targets. In this study, 26 cats were enrolled. Metagenomics of fecal bacterial microbiota and Serum untargeted metabolomics was performed. Compared to healthy cats, those with HCM exhibited significant gut microbiota dysbiosis, including decreased abundances of Campilobacterota, unclassified_k_norank_d_Bacteria, Blautia, Helicobacter, and Ruminococcus_torques_group, while Romboutsia and Lactococcus were enriched in the HCM group. Romboutsia and Lactococcus were identified as characteristic genera in the HCM cat. Significant alterations were observed in energy metabolism pathways, phospholipids, nucleotide metabolism, deoxycorticosterone acetate, propionate, DOCA and several amino acids, which may serve as potential biomarkers for feline HCM. Correlation analysis showed Blautia was associated with serum norepinephrine levels; Helicobacter showed a significant positive correlation with acylcarnitines and amino acid metabolites; Helicobacter and Romboutsia were significantly negatively correlated with phospholipid metabolites. While Ruminococcus_torques_group was significantly negatively correlated with phospholipid metabolites. Romboutsia was significant positive correlation with serum phospholipid metabolites. Lactococcus also showed a significant positive correlation with multiple lipid metabolites.肠道微生物群失调及其代谢产物与心血管疾病密切相关。肥厚型心肌病（Hypertrophic cardiomyopathy, HCM）是最常见的猫科动物心血管疾病之一，同时可作为人类肥厚型心肌病的研究模型。本研究借助多组学分析手段，可对肠道微生物组、代谢组与疾病状态进行整合分析，以挖掘潜在的机制关联、诊断生物标志物及治疗靶点。本研究共纳入26只家猫，对其粪便细菌菌群开展宏基因组测序，并进行血清非靶向代谢组学检测。与健康家猫相比，患HCM的家猫存在显著的肠道菌群失调：弯曲菌门（Campilobacterota）、未分类_k_norank_d_Bacteria、布劳特氏菌属（Blautia）、螺杆菌属（Helicobacter）以及瘤胃球菌torques群（Ruminococcus_torques_group）的相对丰度显著降低，而罗姆布茨菌属（Romboutsia）与乳球菌属（Lactococcus）在HCM组中富集。罗姆布茨菌属与乳球菌属被鉴定为患HCM家猫的特征菌群属。研究发现，能量代谢通路、磷脂类物质、核苷酸代谢、醋酸脱氧皮质酮（deoxycorticosterone acetate, DOCA）、丙酸（propionate）以及多种氨基酸的水平发生显著变化，这些物质或可作为猫科动物HCM的潜在生物标志物。相关性分析结果显示：布劳特氏菌属与血清去甲肾上腺素水平存在关联；螺杆菌属与酰基肉碱类及氨基酸代谢产物呈显著正相关；螺杆菌属、罗姆布茨菌属与瘤胃球菌torques群均与磷脂类代谢产物呈显著负相关；罗姆布茨菌属与血清磷脂类代谢产物呈显著正相关；乳球菌属则与多种脂质代谢产物呈显著正相关。