Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function.
Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function.
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排便频率异常的一般健康个体表现出与肾功能下降相关的微生物来源的血液代谢物的富集。
DOI：
10.1101/2023.03.04.531100
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Gibbons,SeanM
中科院分区：
文献类型：
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作者：
Johnson-Martínez,JohannesP;Diener,Christian;Levine,AnneE;Wilmanski,Tomasz;Suskind,DavidL;Ralevski,Alexandra;Hadlock,Jennifer;Magis,AndrewT;Hood,Leroy;Rappaport,Noa;Gibbons,SeanM
肠道运动频率（BMF）与人类肠道微生物组组成的变化和许多慢性疾病有关，如代谢紊乱，神经退行性疾病，慢性肾脏疾病（CKD）和其他肠道病理学，如肠易激综合征和炎症性肠病。较低的BMF（便秘）可能导致肠道屏障完整性受损，并在微生物群中从糖分解发酵转变为蛋白水解发酵，从而产生微生物衍生的毒素，这些毒素可能进入循环并对器官系统造成损害。然而，BMF，肠道微生物代谢和慢性疾病的早期发展和进展之间的联系仍有待研究。在这里，我们研究了BMF变异的表型影响，在一个队列的一般健康，社区居住的成年人与详细的临床，生活方式和多组学数据。我们发现，BMF组之间微生物来源的血浆代谢产物、肠道细菌属、临床化学和生活方式因素存在显著差异，这些差异与炎症、心脏代谢健康、肝功能和CKD严重程度和进展有关。我们发现，较高的血浆3-吲哚硫酸酯（3-IS）水平（一种与便秘相关的微生物衍生代谢物）反过来与估计的肾小球滤过率（eGFR）呈负相关，eGFR是肾功能的一种指标。因果中介分析显示，BMF对eGFR的影响显著介导3-IS。最后，我们确定了与BMF变化相关的自我报告的饮食，生活方式和心理因素，这表明了减轻便秘和腹泻的几个常识性策略。总体而言，我们认为，异常的BMF是慢性疾病发展中一个未被充分认识的风险因素，即使在其他健康人群中也是如此。
Bowel movement frequency (BMF) has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome and inflammatory bowel disease. Lower BMF (constipation) can lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, the connections between BMF, gut microbial metabolism, and the early-stage development and progression of chronic disease remain underexplored. Here, we examined the phenotypic impact of BMF variation in a cohort of generally-healthy, community dwelling adults with detailed clinical, lifestyle, and multi-omic data. We showed significant differences in microbially-derived blood plasma metabolites, gut bacterial genera, clinical chemistries, and lifestyle factors across BMF groups that have been linked to inflammation, cardiometabolic health, liver function, and CKD severity and progression. We found that the higher plasma levels of 3-indoxyl sulfate (3-IS), a microbially-derived metabolite associated with constipation, was in turn negatively associated with estimated glomerular filtration rate (eGFR), a measure of kidney function. Causal mediation analysis revealed that the effect of BMF on eGFR was significantly mediated by 3-IS. Finally, we identify self-reported diet, lifestyle, and psychological factors associated with BMF variation, which indicate several common-sense strategies for mitigating constipation and diarrhea. Overall, we suggest that aberrant BMF is an underappreciated risk factor in the development of chronic diseases, even in otherwise healthy populations.