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Background. Increasing evidences have reported gut microbiota dysbiosis in many diseases, including chronic kidney disease and pediatric idiopathic nephrotic syndrome (INS). There is lack evidence of intestinal microbiota dysbiosis in adults with INS, however. Here, we to address the association between the gut microbiome and INS. Methods. Stool samples of 35 adult INS patients and 35 healthy volunteers were collected. Total bacterial DNA was extracted, and the V4 regions of the bacterial 16S ribosomal RNA gene were sequenced. The fecal microbiome was analyzed using bioinformatics. The correlation analysis between altered taxa and clinical parameters was also included. Results. We found that microbial diversity in the gut was reduced in adult patients with INS. Acidobacteria, Negativicutes, Selenomonadales, Veillonellaceae, Clostridiaceae, Dialister, Rombousia, Ruminiclostridium, Lachnospira, Alloprevotella, Clostridium sensu stricto, Megamonas, and Phascolarctobacterium were significantly reduced, while Pasteurellales, Parabacteroides, Bilophila, Enterococcus, Eubacterium ventriosum, and Lachnoclostridium were markedly increased in patients with INS. In addition, Burkholderiales, Alcaligenaceae, and Barnesiella were negatively correlated with serum creatinine. Blood urea nitrogen levels were positively correlated with Christensenellaceae, Bacteroidales_S24.7, Ruminococcaceae, Ruminococcus, and Lachnospiraceae_NK4A136, but were negatively correlated with Flavonifractor_plautii and Erysipelatoclostridium_ramosum. Enterobacteriales, Enterobacteriaceae, Porphyromonadaceae, Escherichia/Shigella, Parabacteroides, and Escherichia_coli were positively correlated with albumin. Proteinuria was positively correlated with Verrucomicrobia, Coriobacteriia, Thermoleophilia, Ignavibacteria, Coriobacteriales, Nitrosomonadales, Coriobacteriaceae, and Blautia, but was negatively correlated with Betaproteobacteria, Burkholderiales, and Alcaligenaceae. Conclusion. Our findings show compositional alterations of intestinal microbiota in adult patients with INS and correlations between significantly altered taxa and clinical parameters, which points out the direction for the development of new diagnostics and therapeutic approaches targeted intestinal microbiota. [ABSTRACT FROM AUTHOR]

Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed. [ABSTRACT FROM AUTHOR]

Gut microbiota has a strong influence on the onset and development of systemic lupus erythematosus (SLE), and several studies have demonstrated the effectiveness of microbiota-derived butyrate to ameliorate SLE. However, the roles of butyrate on gut microbiota in SLE are not understood. Using MRL/lpr lupus-prone mice, we examined gut microbiota profiles after butyrate treatment by 16S rRNA sequencing. Alterations in intestinal microbiome in mice with lupus-like disease were mainly characterized by a reduction in microbial diversity, with an increased abundance of Bacteroidetes and a decrease of Firmicutes. Treatment of lupus-prone mice with butyrate resulted in increased abundance of Firmicutes ( P = 0.003), Clostridia ( P = 0.005), Clostridiales ( P = 0.005), Lachnospiraceae ( P = 0.009), Ruminococcaceae ( P = 0.021), Peptostreptococcaceae ( P = 0.021), Ruminiclostridium ( P = 0.016), Oscillibacter ( P = 0.048), Romboutsia ( P = 0.025), Lachnoclostridium ( P = 0.012), Coprococcus ( P = 0.015), Ruminococcus ( P = 0.011), Clostridium leptum ( P < 0.05), and Dorea&#95;spp . ( P = 0.019), and a reduced proportion of Bacteroidetes ( P = 0.004), Bacteroidia ( P = 0.004), and Bacteroidales ( P = 0.004). Further, butyrate supplementation could ameliorate kidney damage. Overall, this study suggests that gut microbiota alterations occur in MRL/lpr lupus-prone mice following treatment with butyrate. Butyrate supplementation ameliorated gut microbiota dysbiosis. These findings support the use of butyrate and butyrate-producing bacteria as potential treatments for SLE., (Copyright © 2020 He, Xu, Xu, Zhao, Lin, Zhou and Nie.)

We evaluated differences in the compositions of faecal microbiota between 52 end stage renal disease (ESRD) patients and 60 healthy controls in southern China using quantitative real-time polymerase chain reaction (qPCR) and high-throughput sequencing (16S ribosomal RNA V4-6 region) methods. The absolute quantification of total bacteria was significantly reduced in ESRD patients (p < 0.01). In three enterotypes, Prevotella was enriched in the healthy group whereas Bacteroides were prevalent in the ESRD group (LDA score > 4.5). 11 bacterial taxa were significantly overrepresented in samples from ESRD and 22 bacterial taxa were overrepresented in samples from healthy controls. The butyrate producing bacteria, Roseburia, Faecalibacterium, Clostridium, Coprococcus and Prevotella were reduced in the ESRD group (LDA values > 2.0). Canonical correspondence analysis (CCA) indicated that Cystatin C (CysC), creatinine and eGFR appeared to be the most important environmental parameters to influence the overall microbial communities. In qPCR analysis, The butyrate producing species Roseburia spp., Faecalibacterium prausnitzii, Prevotella and Universal bacteria, were negatively related to CRP and CysC. Total bacteria in faeces were reduced in patients with ESRD compared to that in healthy individuals. The enterotypes change from Prevotella to Bacteroides in ESRD patients. The gut microbiota was associated with the inflammatory state and renal function of chronic kidney disease.

To quantify Fusobacterium spp., Enterococcus faecalis (E.faecalis), Enterotoxigenic Bacteroides fragilis (ETBF), and Enteropathogenic Escherichia coli in colorectal cancer (CRC) patients and their possible association with CRC clinicopathogical features, we collected the resected tumors and adjacent normal tissues (N) from 97 CRC patients. 48 age- and sex-matched healthy controls (HC) were also recruited. Real-time PCR was used for bacterial quantification. The median abundance ofFusobacterium spp.(p < 0.001, vs. N; p < 0.01,vs. HC), E.faecalis (p < 0.05, vs. N; p < 0.01, vs. HC) and ETBF (p < 0.001, vs. N; p < 0.05,vs. HC) in tumor tissues was significantly higher than that detected in normal tissue and HC. E.faecalis was detected in 95.88% of tumors and 93.81% of adjacent tissues. Fusobacterium spp. was detected in 72.16% of tumors and 67.01% of adjacent tissues. The combined E.faecalis and Fusobacterium spp. were detected in 70.10% of tumors and 36.08% of adjacent normal tissues. All four bacteria were detected in 33.72% and 22.09% of paired tumor and adjacent normal tissues, respectively. E.faecalis and Fusobacterium spp. are enriched in both tumor and adjacent tissue of CRC patients when compared to HC, suggesting that it is possible to be previously undetected changes in the pathohistologically normal colon tissue in the proximity of the tumor.

Background and Aim: Information describing the efficacy and safety of infliximab (IFX) for Crohn's disease (CD) in China is limited. The aim of this study was to report response rates, relapse rates after IFX-induced remission, and adverse events, and identify factors associated with relapse in a cohort of CD patients treated with IFX in a Chinese center., Patients and Methods: Clinical data of CD patients treated with two or more infusions of IFX from July 2010 to February 2013 at Nanfang Hospital (Guangzhou, China) were retrieved and analyzed retrospectively. Primary measurements were clinical response rate and relapse rate during 30 weeks of follow-up. Overall adverse events and risk factors related to IFX were evaluated., Results: A total of 70 CD patients were finally included. The clinical response rate was 98.6% at week 2, 97% at week 6, 92.5% at week 14, 84.9% at week 22, and 84.1% at week 30. The remission rate was 55.7% at week 2, 94% at week 6, 92.5% at week 14, 82.7% at week 22, and 77.3% at week 30. Relapse began following the third infusion. The relapse rate was 3.23% at week 6, 6.12% at week 14, 10.53% at week 22, and 8.82% at week 30. Adverse events related to IFX occurred in 32.6% of patients; most were mild and transient. Univariate analysis showed that sex was a significant predictor of clinical relapse., Conclusion: IFX is an effective and safe treatment for CD in Chinese patients. Sex may be an independent predictor of relapse.