PDF(Pubmed)
Abstract：
Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients.
摘要：
越来越多的证据表明，肠道微生物菌群失调与进行性慢性肾病（CKD）相互作用。然而,目前尚无有效的治疗方法可有效抑制进行性CKD.这里,在480名参与者中使用微生物生物学，包括健康对照和1-5期CKD患者，我们确定了与CKD进展患者相关的延伸分类链杆菌-乳杆菌-乳杆菌-乳杆菌-约氏乳杆菌，其丰度与临床肾脏标志物密切相关。在腺嘌呤诱导的CKD大鼠中，左氏乳杆菌的丰度随着进行性CKD而降低。L.johnsonii补充改善肾脏病变。血清吲哚-3-醛（IAld），CKD大鼠肌酐水平与肌酐水平呈显著负相关,使用单侧输尿管梗阻（UUO）和5/6肾切除术（NX）以及晚期CKD患者诱导的大鼠血清降低。用IAld治疗通过抑制CKD或UUO大鼠的芳香烃受体（AHR）信号减轻肾脏病变，和培养的1-羟基芘诱导的HK-2细胞。在AHR缺乏症小鼠和HK-2细胞中，IAld的肾脏保护作用部分减弱。我们的进一步数据表明，用左旋乳杆菌治疗可通过增加血清IAld水平来抑制AHR信号，从而减轻肾脏病变。一起来看,靶向左脑乳杆菌可能逆转CKD患者。这项研究提供了对微生物产生的色氨酸代谢如何影响宿主疾病的更深入的了解，并发现了CKD患者预防性和治疗性治疗的潜在途径。
