The gut microbiota is involved in various physiological functions, and disturbances in the host-microbiome have been proven to contribute to the dysfunction of gut; however, whether microbiota participates in the pathogenesis of constipation remains unclear. In this study, we extracted and analyzed microbiota in feces from constipated donors who had undergone effective therapy with fecal microbiota transplantation, transplanted microbiota into pseudo-germ-free mice, and measured gut motility. These mice presented with lower pellet frequency and water percentage, smaller pellet size, delayed gastrointestinal transit time, and weaker spontaneous contractions of colonic smooth muscle. To determine the mechanism underlying delayed gut motility, microbial metabolites were measured. Short chain fatty acids and secondary bile acids were decreased in mice receiving microbiota from constipated donors. Moreover, the compositional changes of gut microbiota in constipated patients were identified, including the operational taxonomic unit, and the species richness and α diversity were much greater than those in healthy volunteers. These findings suggest that alterations of the microbiome might affect gut motility via altered microbial-derived metabolites in the development of constipation, and the restoration of disturbed microbiota might improve the clinical phenotype. This study indicates that regulating the intestinal environment may be a novel therapy strategy for constipation.

Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.

To investigate the pattern of brain volume changes in patients with end-stage renal disease (ESRD) using voxel-based morphometry (VBM) and correlation with clinical and neuropsychological (NP) tests. Fifty seven ESRD patients with no anatomical abnormalities in conventional magnetic resonance imaging [24 patients with abnormal NP scores, 16 male, 39 ± 12 years; 33 patients with normal NP scores, 23 male, 35 ± 9.7 years] and 22 age- and gender-matched healthy controls (14 male, 36 ± 10.1 years) were recruited in this study. Results from VBM analysis were analyzed with ANOVA test among 3 groups (controls, minimal nephro-encephalopathy group, non-nephro-encephalopathy group). Multiple linear regression analysis was used to investigate the effect of serum urea and creatinine, and dialysis duration on the brain volumes in ESRD patients. Correlation analysis was performed to investigate the association between NP scores with the brain volumes in ESRD patients. Compared with healthy controls, ESRD patients showed diffusely decreased gray matter volume that further decreased in the presence of encephalopathy. Multiple linear regression results showed that serum urea was negatively associated with changes in gray matter volume in many regions, while dialysis duration was negatively associated with some white matter volume changes (All P < 0.05, AlphaSim correction). NP scores correlated with some decreased gray matter volume in ESRD patients (All P < 0.05, AlphaSim correction). No correlation was found between white matter volume and any NP test scores in ESRD patients. This study found predominantly decreased gray matter volume in ESRD patients, which was associated with neurocognitive dysfunction. Serum urea level may be a risk factor for decreased gray matter in ESRD patients.