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Endocrine ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32246318


PURPOSE: Oral microbiota maintains a dynamic ecological balance with the host. However, a disruption in this balance can lead to oral diseases such as dental caries and periodontitis. Several studies suggest differences in microbial composition in the oral cavity between patients with T2DM and nondiabetic patients. However, there is inadequate oral microbiome-related data from Chinese patients with T2DM, and the difference in microbiome profile between Chinese patients with T2DM and other ethnicities needs to be investigated further. METHOD: Oral swab samples were collected from 280 adult patients with T2DM and 162 healthy controls. Illumina sequencing was performed on oral samples targeting V1-V2 region of 16S rRNA gene and sequence analysis was carried in the QIIME. RESULTS: Patients with T2DM and healthy cohorts exhibited distinct oral microbial clusters based on principal coordinate analysis (PCoA). The Firmicutes/Bacteroidetes ratio increased in T2DM and T2DM patients presented significantly higher numbers of Neisseria, Streptococcus, Haemophilus, and Pseudomonas genera, and lower numbers of Acinetobacteria compared with healthy controls. When compared with the available published data of oral and gut microbiome associated with T2DM patients, we found the ratio of Firmicutes/Bacteroidetes and the abundance of Haemophilus could be a specific microbial biomarker in Chinese patients with T2DM. CONCLUSIONS: Our study revealed a significant difference in the oral microbiota between T2DM patients and healthy individuals. We identified 25 taxa, including 6 genera, with significant difference in abundance between T2DM and healthy controls.

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.

Circ Res ; 126(7): 839-853, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32078445


RATIONALE: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt-induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. OBJECTIVE: To reveal the roles and mechanisms of intestinal flora in hSIH development. METHODS AND RESULTS: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. CONCLUSIONS: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

Diabetes ; 69(4): 760-770, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31974145


Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

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.