Ikee Ryota, Sasaki Naomi, Yasuda Takuji, Fukazawa Sawako
Sapporo Nephrology Satellite Clinic, 9-2-15, Hassamu 6-jo, Nishi-ku, Sapporo 063-0826, Japan.
Sapporo Nephrology Clinic, 20-2-12, Nishimachikita, Nishi-ku, Sapporo 063-0061, Japan.
Microorganisms. 2020 Nov 25;8(12):1862. doi: 10.3390/microorganisms8121862.
Gut dysbiosis has been implicated in the progression of chronic kidney disease (CKD). Alterations in the gut environment induced by uremic toxins, the dietary restriction of fiber-rich foods, and multiple drugs may be involved in CKD-related gut dysbiosis. CKD-related gut dysbiosis is considered to be characterized by the expansion of bacterial species producing precursors of harmful uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, and the contraction of species generating beneficial short-chain fatty acids, such as butyrate. Gut-derived uremic toxins cause oxidative stress and pro-inflammatory responses, whereas butyrate exerts anti-inflammatory effects and contributes to gut epithelial integrity. Gut dysbiosis is associated with the disruption of the gut epithelial barrier, which leads to the translocation of endotoxins. Research on CKD-related gut dysbiosis has mainly focused on chronic inflammation and consequent cardiovascular and renal damage. The pathogenic relationship between CKD-related gut dysbiosis and constipation has not yet been investigated in detail. Constipation is highly prevalent in CKD and affects the quality of life of these patients. Under the pathophysiological state of gut dysbiosis, altered bacterial fermentation products may play a prominent role in intestinal dysmotility. In this review, we outline the factors contributing to constipation, such as the gut microbiota and bacterial fermentation; introduce recent findings on the pathogenic link between CKD-related gut dysbiosis and constipation; and discuss potential interventions. This pathogenic link needs to be elucidated in more detail and may contribute to the development of novel treatment options not only for constipation, but also cardiovascular disease in CKD.
肠道微生物群失调与慢性肾脏病(CKD)的进展有关。尿毒症毒素、富含纤维食物的饮食限制以及多种药物引起的肠道环境改变可能与CKD相关的肠道微生物群失调有关。CKD相关的肠道微生物群失调被认为具有以下特征:产生有害尿毒症毒素前体(如硫酸吲哚酚和对甲酚硫酸盐)的细菌种类增加,以及产生有益短链脂肪酸(如丁酸)的细菌种类减少。肠道来源的尿毒症毒素会引起氧化应激和促炎反应,而丁酸则具有抗炎作用并有助于维持肠道上皮完整性。肠道微生物群失调与肠道上皮屏障的破坏有关,这会导致内毒素移位。关于CKD相关肠道微生物群失调的研究主要集中在慢性炎症以及随之而来的心血管和肾脏损害。CKD相关肠道微生物群失调与便秘之间的致病关系尚未得到详细研究。便秘在CKD患者中非常普遍,会影响这些患者的生活质量。在肠道微生物群失调的病理生理状态下,改变的细菌发酵产物可能在肠道运动障碍中起重要作用。在这篇综述中,我们概述了导致便秘的因素,如肠道微生物群和细菌发酵;介绍了关于CKD相关肠道微生物群失调与便秘之间致病联系的最新发现;并讨论了潜在的干预措施。这种致病联系需要更详细地阐明,可能有助于开发不仅针对便秘,而且针对CKD患者心血管疾病的新治疗方案。
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