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Biochim Biophys Acta Mol Basis Dis ; 1866(6): 165764, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32169506


Recent studies have shown that laboratory murine autoimmunity models under the same environment display different outcomes. We established diabetic nephropathy model mice under the same environment using the classic streptozotocin method. Renal dysfunction was different among the mice. Proteinuria was more significant in the severe proteinuria group (SP) than in the mild proteinuria group (MP). We hypothesized a role for the gut microbiota in the outcome and reproducibility of induced DN models. 16S rDNA gene sequencing technology was used to analyze the differences in the gut microbiota between the two groups. Here, through fecal microbiota transplantation (FMT) and gas chromatography mass spectrometry (GC-MS), we verified the role of the gut microbiota and its short-chain fatty acid (SCFA) generation in DN mouse renal dysfunction. In the SP group, there was a reduced abundance of Firmicutes (P < 0.0001), and the dominant genus Allobaculum [linear discriminant analysis (LDA) >3, P < 0.05] was positively correlated with body weight (Rho = 0.767, P < 0.01) and blood glucose content (Rho = 0.648, P < 0.05), while the dominant genus Anaerosporobacter (LDA > 3, P < 0.05) was positively correlated with 24-hour urinary protein content (Rho = 0.773, P < 0.01). In the MP group, the dominant genus Blautia (LDA > 3, P < 0.05) was negatively correlated with 24-hour urinary protein content (Rho = -0.829, P < 0.05). The results indicated that Allobaculum and Anaerosporobacter may worsen renal function, while Blautia may be a protective factor in DN. These findings suggested that the gut microbiota may contribute to the heterogeneity of the induced response since we observed potential disease-associated microbial taxonomies and correlations with DN.

J Transl Med ; 17(1): 228, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315634


BACKGROUND: Chronic kidney disease (CKD) is a universal chronic disease in China. The balance of the gut microbiome is highly crucial for a healthy human body, especially for the immune system. However, the relationship between the gut microbiome and CKD has not yet been clarified. METHODS: A total of 122 patients were recruited for this study. Among them, 24 patients were diagnosed with CKD5 but did not receive hemodialysis therapy, 29 patients were diagnosed with CKD5 and received hemodialysis therapy and 69 were matched healthy controls. The gut microbiome composition was analyzed by a 16S rRNA (16S ribosomal RNA) gene-based sequencing protocol. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) technology was used to evaluate the levels of microbiome-related protein-binding uremic toxins level, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), in the patients. RESULTS: We compared the gut microbiome results of 122 subjects and established a correlation between the gut microbiome and IS and PCS levels. The results indicated that alpha and beta diversity were different in patients with CKD5 than in the healthy controls (p < 0.01). In comparison to healthy controls, CKD5 patients exhibited a significantly higher relative abundance of Neisseria (p < 0.001), Lachnoclostridium (p < 0.001) and Bifidobacterium (p < 0.001). Faecalibacterium (p < 0.001) displayed a notably lower relative abundance for CKD5 patients both with and without hemodialysis than for controls. It was also found that the concentrations of IS and PCS were correlated with the gut microbiome. CONCLUSIONS: Our results indicate that CKD5 patients both with and without hemodialysis had dysbiosis of the gut microbiome and that this dysbiosis was associated with an accumulation of IS and PCS. These results may support further clinical diagnosis to a great extent and help in developing potential probiotics to facilitate the treatment of CKD5.

J Nephrol ; 32(2): 265-272, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30588573


BACKGROUND: The relationship between oral activated charcoal (OAC) and hyperphosphatemia and vascular calcification is not completely clear. We observed and recorded the effects of OAC on hyperphosphatemia and vascular calcification in stage 3-4 chronic kidney disease (CKD). METHODS: In a randomized controlled study, we included 97 patients with stage 3-4 CKD. In the first phase of the experiment, the patients were randomly divided into the OAC group and placebo group. The endpoint of this phase was the development of hyperphosphatemia. The patients with hyperphosphatemia were selected into the second phase of the study. These patients underwent coronary artery multidetector computed tomography (MDCT) and were randomly divided into three groups: the OAC group, the calcium carbonate (CC) group and the lanthanum carbonate (LC) group. RESULTS: The first and second phases of the experiment were followed for 12 months. In the first phase of the experiment, there was a statistically significant difference in the proportion of patients with hyperphosphatemia between the OAC and placebo groups (28.57% vs. 79.17%, X2 = 24.958, P = 0.000). In the second phase, the differences in coronary calcification score (CACS) between the OAC group, the CC group and the LC group were statistically significant (525.5 ± 104.2 vs 688.1 ± 183.7 vs 431.4 ± 122.5, P < 0.01). CONCLUSION: Oral activated charcoal effectively delays the onset of hyperphosphatemia in patients with chronic kidney disease. OAC appears to delay the development of vascular calcifications in stage 3-4 CKD patients.

Carbonato de Cálcio/administração & dosagem , Carvão Vegetal/administração & dosagem , Quelantes/administração & dosagem , Hiperfosfatemia/prevenção & controle , Lantânio/administração & dosagem , Fosfatos/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Calcificação Vascular/prevenção & controle , Administração Oral , Adulto , Idoso , Biomarcadores/sangue , Carbonato de Cálcio/efeitos adversos , Carvão Vegetal/efeitos adversos , Quelantes/efeitos adversos , Feminino , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/diagnóstico , Hiperfosfatemia/etiologia , Lantânio/efeitos adversos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/etiologia