The Dietary Fiber Inulin Slows Progression of Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD) in a Rat Model of CKD
Annabel Biruete, Neal X. Chen, Corinne E. Metzger, Shruthi Srinivasan, Kalisha O'Neill, Paul B. Fallen, Austin Fonseca, Hannah E. Wilson, Henriette de Loor, Pieter Evenepoel, Kelly S. Swanson, Matthew R. Allen, Sharon M. Moe
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Abstract
Chronic kidney disease (CKD)–mineral bone disorder (CKD-MBD) leads to fractures and cardiovascular disease. Observational studies suggest beneficial effects of dietary fiber on both bone and cardiovascular outcomes, but the effect of fiber on CKD-MBD is unknown. To determine the effect of fiber on CKD-MBD, we fed the Cy/+ rat with progressive CKD a casein-based diet of 0.7% phosphate with 10% inulin (fermentable fiber) or cellulose (non-fermentable fiber) from 22 weeks to either 30 or 32 weeks of age (~30% and ~15% of normal kidney function; CKD 4 and 5). We assessed CKD-MBD end points of biochemistry, bone quantity and quality, cardiovascular health, and cecal microbiota and serum gut-derived uremic toxins. Results were analyzed by two-way analysis of variance (ANOVA) to evaluate the main effects of CKD stage and inulin, and their interaction. The results showed that in CKD animals, inulin did not alter kidney function but reduced the increase from stage 4 to 5 in serum levels of phosphate and parathyroid hormone, but not fibroblast growth factor-23 (FGF23). Bone turnover and cortical bone parameters were similarly improved but mechanical properties were not altered. Inulin slowed progression of aorta and cardiac calcification, left ventricular mass index, and fibrosis. To understand the mechanism, we assessed intestinal microbiota and found changes in alpha and beta diversity and significant changes in several taxa with inulin, together with a reduction in circulating gut derived uremic toxins such as indoxyl sulfate and short-chain fatty acids. In conclusion, the addition of the fermentable fiber inulin to the diet of CKD rats led to a slowed progression of CKD-MBD without affecting kidney function, likely mediated by changes in the gut microbiota composition and lowered gut-derived uremic toxins. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
膳食纤维菊粉可延缓慢性肾脏病大鼠模型中慢性肾脏病-矿物质骨病(CKD-MBD)的进展
慢性肾脏疾病(CKD) -矿物质骨紊乱(CKD‐MBD)导致骨折和心血管疾病。观察性研究表明,膳食纤维对骨骼和心血管结果都有有益的影响,但纤维对CKD - MBD的影响尚不清楚。为了确定纤维对CKD - MBD的影响,我们在22周龄至30或32周龄期间(正常肾功能的~30%和~15%),给患有进行性CKD的Cy/+大鼠喂食含有0.7%磷酸盐和10%菊粉(可发酵纤维)或纤维素(不可发酵纤维)的酪蛋白饲粮。我们评估了CKD - MBD的生化终点、骨骼数量和质量、心血管健康、盲肠微生物群和血清肠道源性尿毒症毒素。结果通过双向方差分析(ANOVA)来评估CKD分期和菊粉的主要影响及其相互作用。结果显示,在CKD动物中,菊粉没有改变肾功能,但降低了从4期到5期血清磷酸盐和甲状旁腺激素水平的升高,但对成纤维细胞生长因子- 23 (FGF23)没有影响。骨转换和骨皮质参数同样得到改善,但力学性能没有改变。菊粉减缓了主动脉和心脏钙化、左心室质量指数和纤维化的进展。为了了解这一机制,我们评估了肠道微生物群,发现在菊粉的作用下,α和β多样性发生了变化,几个分类群发生了显著变化,同时循环肠道来源的尿毒症毒素(如硫酸吲哚酚和短链脂肪酸)减少。总之,在CKD大鼠的饮食中添加可发酵纤维菊粉可以减缓CKD - MBD的进展,而不影响肾功能,可能是通过改变肠道微生物群组成和降低肠道源性尿毒症毒素介导的。©2023作者。JBMR Plus由Wiley期刊有限责任公司代表美国骨与矿物研究协会出版。
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