慢性肾病儿童的细菌代谢物与心血管风险

IF 2.4 Q1 PEDIATRICS Molecular and cellular pediatrics Pub Date : 2021-10-22 DOI:10.1186/s40348-021-00126-8
Julia Schlender, Felix Behrens, Victoria McParland, Dominik Müller, Nicola Wilck, Hendrik Bartolomaeus, Johannes Holle
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引用次数: 2

摘要

心血管并发症是慢性肾脏疾病(CKD)显著发病率和死亡率的主要原因。糖尿病和高血压等经典心血管危险因素无疑在成人CKD患者心血管疾病(CVD)的发展中起着重要作用;然而,心血管疾病在没有这些危险因素的CKD患儿中同样突出。因此,CVD的ckd特异性病理生理机制仍不完全清楚。鉴于此,研究儿童CKD提供了一个独特的机会,可以更具体地分析CKD相关的CVD机制,并有助于揭示新的治疗靶点。在这里,我们全面回顾了人类肠道微生物群和营养物质微生物代谢与宿主免疫和心血管终末器官损伤的相互作用。人类肠道微生物群在整个生命过程中受到内源性因素和环境因素的进化制约和修饰。慢性疾病,如慢性肾病,会对肠道微生物群的组成和功能造成严重破坏,并导致疾病相关的生态失调。这种生态失调和伴随的结肠上皮细胞生化稳态的丧失可能是不良饮食(如低纤维摄入)、药物和潜在疾病的结果。由于生态失调,促进蛋白水解发酵的细菌增加,而促进糖水解发酵的细菌减少,肠道屏障的完整性受到干扰(漏肠)。这些变化破坏了肠道内局部代谢物的稳态,减少了有益的短链脂肪酸(SCFAs)的产生。此外,增强的蛋白质水解发酵产生不健康水平的微生物衍生的有毒代谢物,这些代谢物进一步积聚在体循环中,导致肾功能受损。我们描述了CKD中全身性炎症增加的可能机制,这与SCFA缺乏和尿毒症毒素积累的联合作用有关。在未来,对主要由免疫失调和炎症介导的肠-肾-心相互作用的更全面和机制的理解,可能使我们能够更有针对性地靶向肠道微生物群,以减轻ckd相关的合共病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Bacterial metabolites and cardiovascular risk in children with chronic kidney disease.

Cardiovascular complications are the major cause of the marked morbidity and mortality associated with chronic kidney disease (CKD). The classical cardiovascular risk factors such as diabetes and hypertension undoubtedly play a role in the development of cardiovascular disease (CVD) in adult CKD patients; however, CVD is just as prominent in children with CKD who do not have these risk factors. Hence, the CKD-specific pathophysiology of CVD remains incompletely understood. In light of this, studying children with CKD presents a unique opportunity to analyze CKD-associated mechanisms of CVD more specifically and could help to unveil novel therapeutic targets.Here, we comprehensively review the interaction of the human gut microbiome and the microbial metabolism of nutrients with host immunity and cardiovascular end-organ damage. The human gut microbiome is evolutionary conditioned and modified throughout life by endogenous factors as well as environmental factors. Chronic diseases, such as CKD, cause significant disruption to the composition and function of the gut microbiome and lead to disease-associated dysbiosis. This dysbiosis and the accompanying loss of biochemical homeostasis in the epithelial cells of the colon can be the result of poor diet (e.g., low-fiber intake), medications, and underlying disease. As a result of dysbiosis, bacteria promoting proteolytic fermentation increase and those for saccharolytic fermentation decrease and the integrity of the gut barrier is perturbed (leaky gut). These changes disrupt local metabolite homeostasis in the gut and decrease productions of the beneficial short-chain fatty acids (SCFAs). Moreover, the enhanced proteolytic fermentation generates unhealthy levels of microbially derived toxic metabolites, which further accumulate in the systemic circulation as a consequence of impaired kidney function. We describe possible mechanisms involved in the increased systemic inflammation in CKD that is associated with the combined effect of SCFA deficiency and accumulation of uremic toxins. In the future, a more comprehensive and mechanistic understanding of the gut-kidney-heart interaction, mediated largely by immune dysregulation and inflammation, might allow us to target the gut microbiome more specifically in order to attenuate CKD-associated comorbidities.

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