Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis (ICGN). However, an in-depth study on this topic is currently lacking. Herein, we report an ICGN model to address this gap. ICGN was induced via the intravenous injection of cationized bovine serum albumin (c-BSA) into Sprague-Dawley (SD) rats for two weeks, after which mycophenolate mofetil (MMF) and losartan were administered orally. Two and six weeks after ICGN establishment, fecal samples were collected and 16S ribosomal DNA (rDNA) sequencing and untargeted metabolomic were conducted. Fecal microbiota transplantation (FMT) was conducted to determine whether gut normalization caused by MMF and losartan contributed to their renal protective effects. A gradual decline in microbial diversity and richness was accompanied by a loss of renal function. Approximately 18 genera were found to have significantly different relative abundances between the early and later stages, and and were markedly upregulated in both stages. Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN, characterized by the overproduction of indole and kynurenic acid, while the serotonin pathway was reduced. Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces. FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the / (F/B) ratio but did not improve renal function. These findings indicate that ICGN induces serous gut dysbiosis, wherein an altered tryptophan metabolism may contribute to its progression. MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis, which partially contributed to their renoprotective effects.

中文翻译：

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阳离子牛血清白蛋白诱导的实验性免疫复合物肾小球肾炎的动态肠道微生物组-代谢组以及氯沙坦和吗替麦考酚酯对微生物群调节的影响

肠道菌群失调和代谢组失调的动态变化与免疫复合物肾小球肾炎（ICGN）相关。然而，目前缺乏对此主题的深入研究。在此，我们报告了一个 ICGN 模型来解决这一差距。通过向SD大鼠静脉注射阳离子牛血清白蛋白（c-BSA）两周诱导ICGN，然后口服吗替麦考酚酯（MMF）和氯沙坦。 ICGN 建立后两周和六周，收集粪便样本并进行 16S 核糖体 DNA (rDNA) 测序和非靶向代谢组学。进行粪便微生物群移植 (FMT) 以确定 MMF 和氯沙坦引起的肠道正常化是否有助于其肾脏保护作用。微生物多样性和丰富度逐渐下降，伴随着肾功能的丧失。发现大约18个属在早期和晚期之间的相对丰度存在显着差异，并且在两个阶段中均显着上调。非靶向代谢组学表明，ICGN 中色氨酸代谢增强，其特征是吲哚和犬尿酸过量产生，而血清素途径减少。给予氯沙坦和 MMF 可改善微生物失调并减少粪便中吲哚酚结合物的积累。使用施用 MMF 和氯沙坦的动物粪便进行的 FMT 通过降低 / (F/B) 比率改善了肠道生态失调，但没有改善肾功能。这些发现表明 ICGN 会诱导浆液性肠道菌群失调，其中色氨酸代谢的改变可能有助于其进展。 MMF 和氯沙坦显着逆转了肠道微生物和代谢组的失调，这在一定程度上促进了它们的肾脏保护作用。