与心血管疾病相关的肠道微生物群的性别差异

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-01-19 DOI:10.1186/s13293-024-00582-7
Helena Garcia-Fernandez, Antonio P. Arenas-de Larriva, Javier Lopez-Moreno, Francisco M. Gutierrez-Mariscal, Juan L. Romero-Cabrera, Helena Molina-Abril, Jose D. Torres-Peña, Diego Rodriguez-Cano, Maria M. Malagon, Jose M. Ordovas, Javier Delgado-Lista, Pablo Perez-Martinez, Jose Lopez-Miranda, Antonio Camargo
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引用次数: 0

摘要

心血管疾病(CVD),包括冠心病(CHD),在男性中的发病率高于女性。本研究旨在评估患有冠心病的男性和女性之间肠道微生物群的变化,并将这些变化与非冠心病对照组进行对比。我们的研究是在 CORDIOPREV 研究的框架内进行的,该临床试验涉及 837 名男性和 165 名女性心脏病患者。我们将研究结果与 375 名无心血管疾病的参照组(男性 270 人,女性 105 人)进行了对比。我们在 Illumina MiSeq 平台上通过 16S 元基因组学对肠道微生物群进行了检测,并使用 Quiime2 软件对数据进行了处理。我们的研究结果表明,肠道微生物群存在性别差异(β多样性),而α-生物多样性在两性中保持一致。线性判别分析效应大小(LEfSe)分析揭示了与心血管疾病相关的肠道微生物群以性别为中心的改变。此外,利用随机森林(RF)方法,我们发现了七个细菌类群-g_UBA1819(Ruminococcaceae)、g_Bilophila、g_Subdoligranulum、g_Phascolarctobacterium、f_Barnesiellaceae、g_Ruminococcus 和 Ruminococcaceae 家族中的一个未知属(Ruminococcaceae incertae sedis)-是诊断出患有心血管疾病的男性和女性之间的关键判别因素。按性别单独分析时,同样的分类群也是区分冠心病患者和非冠心病患者的关键因素。我们的研究结果表明,肠道微生物群存在与冠心病相关的性别特异性菌群失调,这可能是导致心血管疾病发病率性别差异的原因之一。试验注册 Clinical Trials.gov.Identifier NCT00924937.心血管疾病在男性和女性中的发病率不同,因为男性的发病率更高。此外,人们多年来一直知道,生活在我们肠道中的细菌群落(也称为肠道微生物群)会影响这些疾病的发生。事实上,如今人们已经知道肠道微生物群对动脉粥样硬化发展的影响,而动脉粥样硬化是导致心血管疾病的三大主要原因:冠心病、脑血管疾病和外周动脉疾病的病理过程。这项研究表明,生活在男性肠道中的细菌群落与生活在女性肠道中的细菌群落存在差异,因此这些差异至少可以部分解释男女之间心血管疾病发生频率的差异。我们的研究结果表明,与冠心病相关的肠道微生物群失调似乎具有部分性别特异性,这可能会影响冠心病发病率的性别二态性。此外,在制定旨在减少代谢性疾病和心血管疾病的发病率和复发率的有效策略和疗法时,确定导致代谢性疾病和心血管疾病发病率性别双态性的机制尤为重要。事实上,用于治疗肠道微生物群失调的策略和疗法应具有性别特异性。
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Sex-specific differences in intestinal microbiota associated with cardiovascular diseases
Cardiovascular diseases (CVD), including coronary heart disease (CHD), display a higher prevalence in men than women. This study aims to evaluate the variations in the intestinal microbiota between men and women afflicted with CHD and delineate these against a non-CVD control group for each sex. Our research was conducted in the framework of the CORDIOPREV study, a clinical trial which involved 837 men and 165 women with CHD. We contrasted our findings with a reference group of 375 individuals (270 men, 105 women) without CVD. The intestinal microbiota was examined through 16S metagenomics on the Illumina MiSeq platform and the data processed with Quiime2 software. Our results showed a sex-specific variation (beta diversity) in the intestinal microbiota, while alpha-biodiversity remained consistent across both sexes. Linear discriminant analysis effect size (LEfSe) analysis revealed sex-centric alterations in the intestinal microbiota linked to CVD. Moreover, using random forest (RF) methodology, we identified seven bacterial taxa—g_UBA1819 (Ruminococcaceae), g_Bilophila, g_Subdoligranulum, g_Phascolarctobacterium, f_Barnesiellaceae, g_Ruminococcus, and an unknown genus from the Ruminococcaceae family (Ruminococcaceae incertae sedis)—as key discriminators between men and women diagnosed with CHD. The same taxa also emerged as critical discriminators between CHD-afflicted and non-CVD individuals, when analyzed separately by sex. Our findings suggest a sex-specific dysbiosis in the intestinal microbiota linked to CHD, potentially contributing to the sex disparity observed in CVD incidence. Trial registration Clinical Trials.gov.Identifier NCT00924937. The frequency with which cardiovascular diseases occur differs in men and women as it appears with greater frequency in men. Moreover, it has been known for years that the community of bacteria living in our intestine, also known as the gut microbiota, influences the development of these diseases. Indeed, nowadays it known the influence of the intestinal microbiota in the development of atherosclerosis, the pathological process which is responsible for the three main causes of cardiovascular diseases: coronary heart disease, cerebrovascular disease and peripheral arterial disease. This study shows the differences in the community of bacteria living in the gut of men and those living in the gut of women, so that these differences could explain, at least in part, the differences in the frequency with which cardiovascular diseases appear between men and women. Our results suggest that the dysbiosis of the intestinal microbiota associated with CHD seems to be partially sex-specific, which may influence the sexual dimorphism in its incidence. Moreover, the identification of the mechanisms responsible for sexual dimorphism in the incidence of metabolic and cardiovascular disease is of particular importance when developing effective strategies and therapies aimed at reducing their incidence and recurrence. Indeed, the strategies and therapies used to treat the dysbiosis of the gut microbiota should be sex-specific.
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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