Background Diabetic kidney disease (DKD) and membranous nephropathy (MN) are the two major causes of end-stage renal disease (ESRD). Increasing evidence has shown that intestinal dysbiosis is associated with many diseases. The aim of this study was to explore the composition of the gut microbiome in DKD and MN patients. Methods 16S rRNA gene sequencing was performed on 271 fecal samples (DKD = 129 and MN = 142), and taxonomic annotation of microbial composition and function was completed. Results We observed distinct microbial communities between the two groups, with MN samples exhibiting more severe dysbiosis than DKD samples. Relative increases in genera producing short-chain fatty acids (SCFAs) in DKD and a higher proportion of potential pathogens in MN were the main contributors to the microbiome alterations in the two groups. Five-fold cross-validation was performed on a random forest model, and four operational taxonomic unit (OTU)-based microbial markers were selected to distinguish DKD from MN. The results showed 92.42% accuracy in the training set and 94.52% accuracy in the testing set, indicating high potential for these microbiome-based markers in separating MN from DKD. Overexpression of several amino acid metabolic pathways, carbohydrate metabolism and lipid metabolism was found in DKD, while interconversion of pentose/glucoronate and membrane transport in relation to ABC transporters and the phosphotransferase system were increased in MN. Conclusion The composition of the gut microbiome appears to differ considerably between patients with DKD and those with MN. Thus, microbiome-based markers could be used as an alternative tool to distinguish DKD and MN.
Background. Diabetes mellitus (DM) has become one of the most common chronic metabolic diseases worldwide. Due to the increasing prevalence and various complications, diabetes brings about a huge financial burden to DM patients. Nowadays, more and more studies reveal the relationship between diseases and gut microbial community. We aimed to explore the alteration in composition and function of the gut microbiome in T2DM patients. Methods. A total of 137 patients with diabetes and 179 age- and gender-matched healthy controls selected from the healthy people sample center in the First Affiliated Hospital of Zhengzhou University were divided into the DM group and the Con group, respectively. We collected their venous blood for laboratory tests and stool samples for 16S rRNA sequencing. The comparison between the two groups including both composition and function of the gut microbiome is presented.Results. We found that the α-diversity of bacterial taxa in the DM group had an evident decrease compared to that in the Con group. At the phylum level, the DM group had an obvious decrease of Bacteroidetes and a marked increase of Proteobacteria, Actinobacteria, and Verrucomicrobia. At the genus level, Bacteroides and Prevotella decreased the most while Escherichia-Shigella, Lachnospiraceae_incertae_sedis, Subdoligranulum, Enterococcus, and Klebsiella had different degrees of expansion in the DM group. The ROC based on 246 optimum OTUs had very high test efficiency with an AUC of 92.25% in the training set and 90.48% in the test set. As for prediction of metabolic function, the gut microbiome of DM patients was predicted to be more active in environmental information processing and human diseases but less in metabolism. Conclusion. We observed alteration of composition and function of the gut microbiome in the DM group. These changes may provide a new treatment strategy for DM patients and new research targets.
Patients with neuropathic pain often experience exaggerated pain and anxiety. Central sensitization has been linked with the maintenance of neuropathic pain and may become an autonomous pain generator. Conversely, emerging evidence accumulated that central sensitization is initiated and maintained by ongoing nociceptive primary afferent inputs. However, it remains elusive what mechanisms underlie this phenomenon and which peripheral candidate contributes to central sensitization that accounts for pain hypersensitivity and pain-related anxiety. Previous studies have implicated peripherally localized cGMP-dependent protein kinase I (PKG-I) in plasticity of nociceptors and spinal synaptic transmission as well as inflammatory hyperalgesia. However, whether peripheral PKG-I contributes to cortical plasticity and hence maintains nerve injury–induced pain hypersensitivity and anxiety is unknown. Here, we demonstrated significant upregulation of PKG-I in ipsilateral L3 dorsal root ganglia (DRG), no change in L4 DRG, and downregulation in L5 DRG upon spared nerve injury. Genetic ablation of PKG-I specifically in nociceptors or post-treatment with intervertebral foramen injection of PKG-I antagonist, KT5823, attenuated the development and maintenance of spared nerve injury–induced bilateral pain hypersensitivity and anxiety. Mechanistic analysis revealed that activation of PKG-I in nociceptors is responsible for synaptic potentiation in the anterior cingulate cortex upon peripheral neuropathy through presynaptic mechanisms involving brain-derived neurotropic factor signaling. Our results revealed that PKG-I expressed in nociceptors is a key determinant for cingulate synaptic plasticity after nerve injury, which contributes to the maintenance of pain hypersensitivity and anxiety. Thereby, this study presents a strong basis for opening up a novel therapeutic target, PKG-I, in nociceptors for treatment of comorbidity of neuropathic pain and anxiety with least side effects.
Purpose Little is known about factors that predict dietary adherence among Chinese patients undergoing peritoneal dialysis. We investigated whether self-regulatory fatigue and trait self-control influence dietary adherence among Chinese patients with peritoneal dialysis. Methods A total of 192 Chinese patients undergoing peritoneal dialysis were recruited at two peritoneal dialysis centers. The dietary adherence, trait self-control and self-regulatory fatigue of these patients were assessed using self-administered questionnaires. Clinical data were extracted from the hospital medical records. The significance of several social demographic factors on dietary adherence was analyzed using One-way ANOVA was used to analyze, whereas the association between dietary adherence and self-regulatory fatigue as well as trait self-control were analyzed using Pearson correlation. The independence association between dietary adherence and other influencing factors was assessed using Multivariable linear regression analyses. Results We found that peritoneal dialysis patients only moderately adhere to dietary prescriptions. The top three least adherences were observed for salt intake (1.89±0.36), face of difficulty (2.86±0.26) and fluid restriction adherence intake (2.97±0.30). Multivariable linear regression analysis revealed that education level (β=0.339, P<0.001), residence (β=−0.151, P=0.015), self-regulatory fatigue (β= −0.648, P<0.001), and trait self-control (β=0.118, P=0.022) were independent predictors of dietary adherence. Conclusion Education level and residence strongly influence dietary adherence among Chinese peritoneal dialysis patients. On the other hand, Self-regulatory fatigue and trait self-control are independent predictors of dietary adherence among peritoneal dialysis patients. These findings can guide the enhancement of dietary adherence of peritoneal dialysis patients.
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