The impact of gut fungi and (1→3)-β-d-glucan (BG), a major fungal cell wall component, on uremia was explored by Candida albicans oral administration in bilateral nephrectomy (BiNx) mice because of the prominence of C. albicans in the human intestine but not in mice. As such, BiNx with Candida administration (BiNx-Candida) enhanced intestinal injury (colon cytokines and apoptosis), gut leakage (fluorescein isothiocyanate [FITC]-dextran assay, endotoxemia, serum BG, and bacteremia), systemic inflammation, and liver injury at 48 h postsurgery compared with non-Candida BiNx mice. Interestingly, uremia-induced enterocyte apoptosis was severe enough for gut translocation of viable bacteria, as indicated by culture positivity for bacteria in blood, mesenteric lymph nodes (MLNs), and other organs, which was more severe in BiNx-Candida than in non-Candida BiNx mice. Candida induced alterations in the gut microbiota of BiNx mice as indicated by (i) the higher fungal burdens in the feces of BiNx-Candida mice than in sham-Candida mice by culture methods and (ii) increased Bacteroides with decreased Firmicutes and reduced bacterial diversity in the feces of BiNx-Candida mice compared with non-Candida BiNx mice by fecal microbiome analysis. In addition, lipopolysaccharide plus BG (LPS+BG), compared with each molecule alone, induced high supernatant cytokine levels, which were enhanced by uremic mouse serum in both hepatocytes (HepG2 cells) and macrophages (RAW264.7 cells). Moreover, LPS+BG, but not each molecule alone, reduced the glycolysis capacity and mitochondrial function in HepG2 cells as determined by extracellular flux analysis. Additionally, a probiotic, Lactobacillus rhamnosus L34 (L34), attenuated disease severity only in BiNx-Candida mice but not in non-Candida BiNx mice, as indicated by liver injury and serum cytokines through the attenuation of gut leakage, the fecal abundance of fungi, and fecal bacterial diversity but not fecal Gram-negative bacteria. In conclusion, Candida enhanced BiNx severity through the worsening of gut leakage and microbiota alterations that resulted in bacteremia, endotoxemia, and glucanemia.

中文翻译：

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念珠菌管理加剧了双侧肾切除小鼠尿毒症引起的肠道泄漏，肠道真菌和有机分子对尿毒症的影响

由于念珠菌C的重要性，白色念珠菌口服给予双侧肾切除（BiNx）小鼠探索了肠道真菌和（1→3）-β- d-葡聚糖（BG）（一种主要的真菌细胞壁成分）对尿毒症的影响。人肠中的白色念珠菌，但小鼠中没有。因此，BiNx与念珠菌的给药（BiNx-念珠菌）可增强肠道损伤（结肠细胞因子和细胞凋亡），肠道渗漏（异硫氰酸荧光素[FITC]-葡聚糖测定，内毒素血症，血清BG和菌血症），全身性炎症以及肝损伤与非念珠菌感染相比，术后48小时BiNx小鼠。有趣的是，尿毒症诱导的肠上皮细胞凋亡足以使活菌发生肠道移位，正如血液，肠系膜淋巴结（MLNs）和其他器官中细菌的培养阳性所表明的那样，在BiNx-念珠菌中，这比在非细菌中更为严重。念珠菌BiNx小鼠。念珠菌诱导小鼠BINX的肠道菌群的改变所指示（i）如BiNx-的粪便中的更高的真菌负担念珠菌小鼠比假手术念珠菌小鼠培养方法和（ii）增加的类杆菌具有降低厚壁菌门和减少细菌多样性在BiNx-念珠菌小鼠的粪便中念珠菌BiNx小鼠通过粪便微生物组分析。另外，与单独的每个分子相比，脂多糖加BG（LPS + BG）诱导了较高的上清细胞因子水平，尿毒症小鼠血清在肝细胞（HepG2细胞）和巨噬细胞（RAW264.7细胞）中均增强了细胞因子水平。此外，通过细胞外通量分析确定，LPS + BG（但不是每个分子单独）降低了HepG2细胞的糖酵解能力和线粒体功能。此外，益生菌鼠李糖乳杆菌L34（L34）仅在BiNx-念珠菌小鼠中减轻了疾病的严重程度，而在非念珠菌中没有BiNx小鼠表现为肝损伤和通过减少肠道渗漏，粪便中的真菌丰度和粪便细菌多样性（而非粪便革兰氏阴性细菌）引起的血清细胞因子。总之，念珠菌通过导致肠道菌血症，内毒素血症和葡聚糖血症的肠道泄漏和微生物群变化的恶化而增强了BiNx的严重性。