Abstract:
Gut microbiota-derived uremic toxins (UT) accumulate in patients with chronic kidney disease (CKD). Dietary phosphorus and protein restriction are common in CKD treatment, but the relationship between dietary phosphorus, a key nutrient for the gut microbiota, and protein-derived UT is poorly studied. Thus, we explored the relationship between dietary phosphorus and serum UT in CKD rats. For this exploratory study, we used serum samples from a larger study on the effects of dietary phosphorus on intestinal phosphorus absorption in nephrectomized (Nx, n = 22) or sham-operated (sham, n = 18) male Sprague Dawley rats. Rats were randomized to diet treatment groups of low or high phosphorus (0.1% or 1.2% w/w, respectively) for 1 week, with serum trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS) analyzed by LC-MS. Nx rats had significantly higher levels of serum TMAO, IS, and pCS compared to sham rats (all p < 0.0001). IS showed a significant interaction between diet and CKD status, where serum IS was higher with the high-phosphorus diet in both Nx and sham rats, but to a greater extent in the Nx rats. Serum TMAO (p = 0.24) and pCS (p = 0.34) were not affected by dietary phosphorus levels. High dietary phosphorus intake for 1 week results in higher serum IS in both Nx and sham rats. The results of this exploratory study indicate that reducing dietary phosphorus intake in CKD may have beneficial effects on UT accumulation.
摘要:
肠道微生物来源的尿毒症毒素(UT)在慢性肾脏病(CKD)患者中积累。饮食磷和蛋白质限制在CKD治疗中很常见,但是膳食磷之间的关系,肠道微生物群的关键营养素,和蛋白质来源的UT研究很少。因此,探讨CKD大鼠膳食磷与血清UT的关系。对于这项探索性研究,我们使用了来自更大研究的血清样本,研究了日粮磷对肾切除术中肠磷吸收的影响(Nx,n=22)或假手术(假手术,n=18)雄性SD大鼠。将大鼠随机分为低磷或高磷饮食治疗组(0.1%或1.2%w/w,分别)1周,血清三甲胺氧化物(TMAO),硫酸吲哚酚(IS),和对甲酚硫酸盐(pCS)通过LC-MS分析。Nx大鼠血清TMAO水平明显升高,IS,和pCS与假手术大鼠相比(所有p<0.0001)。IS显示饮食和CKD状态之间存在显著的相互作用,在Nx和假大鼠中,高磷饮食的血清IS较高,但在Nx大鼠中的程度更大。血清TMAO(p=0.24)和pCS(p=0.34)不受日粮磷水平的影响。1周的高饮食磷摄入量导致Nx和假手术大鼠的血清IS较高。这项探索性研究的结果表明,减少CKD中的膳食磷摄入量可能对UT积累具有有益的影响。