Xiao Congmei, Chen Qian, Shuai Menglei, Gao Chang, Gou Wanglong, Miao Zelei, Zhang Ke, Shen Luqi, Liang Xinxiu, Wang Chun, Zhong Haili, Ye Meng, Xu Fengzhe, Tang Jun, Jiang Zengliang, Xi Yue, Fu Yuanqing, Chen Yu-Ming, Zheng Ju-Sheng
Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.
BMC Med. 2025 Aug 8;23(1):468. doi: 10.1186/s12916-025-04307-4.
This study aimed to investigate the prospective association of dairy biomarkers of odd-chain saturated fatty acids (OCFA) with incident carotid artery plaque (CAP) and to explore the potential role of gut microbiota and related metabolites in the above associations.
In the Guangzhou Nutrition and Health Study (GNHS, n = 1211; baseline mean age: 58.7 ± 6.1 years), we investigated the associations of baseline plasma phospholipid OCFAs with CAP incidence and gut microbiota (16S rRNA sequencing) over a median follow-up period of 6.2 years. Westlake Precision Birth Cohort was used to evaluate the potential associations between OCFA and the identified gut microbiota features in a younger population. Associations of OCFAs with CAP, gut microbial alpha diversity, specific genera, and related metabolites were examined using Cox proportional hazards models or linear regression models, with adjustments of potential confounders.
The total OCFA was inversely associated with the incidence of CAP in the GNHS, with a hazard ratio of 0.63 (quartile 4 versus 1: 95% confidence interval [CI]: 0.46, 0.86). Additionally, total OCFA was significantly associated with gut microbial alpha and beta diversity (all P < 0.05). The beta coefficient for the association between total OCFA and the Shannon index was 0.11 (95% CI: 0.06, 0.17). We identified 36 microbial genera significantly associated with total or individual OCFAs (FDR < 0.05). Among these identified genera, the Christensenellaceae R-7 group, an OCFA-positive-related genus, was inversely associated with the prevalence of CAP (P < 0.05). We then identified 13 microbe-derived metabolites significantly associated with both total OCFA and C. R-7 group (FDR < 0.05), including deoxycholic acid and lithocholic acid.
Our results suggest that plasma OCFAs, as objective biomarkers of dairy exposure, are inversely associated with CAP incidence in a Chinese cohort. Further exploration indicates that gut microbiota may be involved in the above association, providing a potential gut microbiota-based intervention target for atherosclerosis.
本研究旨在调查奇数链饱和脂肪酸（OCFA）的乳制品生物标志物与颈动脉斑块（CAP）发生之间的前瞻性关联，并探讨肠道微生物群及其相关代谢产物在上述关联中的潜在作用。
在广州营养与健康研究（GNHS，n = 1211；基线平均年龄：58.7 ± 6.1岁）中，我们在中位随访期6.2年期间，研究了基线血浆磷脂OCFA与CAP发病率及肠道微生物群（16S rRNA测序）之间的关联。利用西湖精准出生队列评估OCFA与年轻人群中已鉴定的肠道微生物群特征之间的潜在关联。使用Cox比例风险模型或线性回归模型，并对潜在混杂因素进行调整，来检验OCFA与CAP、肠道微生物α多样性、特定菌属及相关代谢产物之间的关联。
在GNHS中，总OCFA与CAP发病率呈负相关，风险比为0.63（四分位数4与1相比：95%置信区间[CI]：0.46，0.86）。此外，总OCFA与肠道微生物α和β多样性显著相关（所有P < 0.05）。总OCFA与香农指数之间关联的β系数为0.11（95% CI：0.06，0.17）。我们鉴定出36个与总OCFA或单个OCFA显著相关的微生物属（FDR < 0.05）。在这些已鉴定的菌属中，克里斯滕森菌科R-7组，一个与OCFA呈正相关的菌属，与CAP的患病率呈负相关（P < 0.05）。然后我们鉴定出13种与总OCFA和克里斯滕森菌科R-7组均显著相关的微生物衍生代谢产物（FDR < 0.05），包括脱氧胆酸和石胆酸。
我们的结果表明，血浆OCFA作为乳制品暴露的客观生物标志物，与中国队列中的CAP发病率呈负相关。进一步探索表明，肠道微生物群可能参与了上述关联，为动脉粥样硬化提供了一个潜在的基于肠道微生物群的干预靶点。
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