The regeneration of intestinal epithelial are maintained by continuous differentiation and proliferation of intestinal stem cells (ISCs) under physiological and pathological conditions. However, little is known about the regulatory effect of intestinal microbiota on its recovery ability to repair damaged mucosal barrier. In this study, we established intestinal organoids and lamina propria lymphocytes (LPLs) co-cultured system, plus mice experiments, to explore the protective effect of Lactobacillus reuteri D8 on integrity of intestinal mucosa. We found that only live L. reuteri D8 was effective in protecting the morphology of intestinal organoids and normal proliferation of epithelial stained with EdU under TNF-α treatment, which was also further verified in mice experiments. L. reuteri D8 colonized in the intestinal mucosa and ameliorated intestinal mucosa damage caused by DSS treatment, including improvement of body weight, colon length, pathological change, and proliferation level. The repair process stimulated by L. reuteri D8 was also accompanied with increased numbers of Lgr5 and lysozyme cells both in intestinal organoids and mice intestine. Furthermore, we demonstrated that D8 metabolite indole-3-aldehyde stimulated LPLs to secret IL-22 through aryl hydrocarbon receptor (AhR) and then induced phosphorylation of STAT3 to accelerate proliferation of intestinal epithelial, thus recovering damaged intestinal mucosa. Our findings indicate L. reuteri protects intestinal barrier and activates intestinal epithelial proliferation, which sheds light on treatment approaches for intestinal inflammation based on ISCs with probiotics Lactobacillus and daily probiotic consumption in heath foods.
Objective To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS); to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax ) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low‐volume voids. Patients and methods The study comprised 1271 men aged between 45 and 88 years recruited from 12 centres in Europe, Australia, Canada, Taiwan and Japan over a 2‐year period. Symptom questionnaires, voiding diaries, uroflowmetry and pressure‐flow data were recorded. The relationship between uroflow variables and symptoms, Qmax and BOO, and the diagnostic performance of low volume voids were analysed. Results The relationship between symptoms and uroflow variables was poor. The mean difference between home‐recorded and clinic‐recorded voided volumes was −48 mL. Qmax was significantly lower in those with BOO (9.7 mL/s for void 1) than in those with no obstruction (12.6 mL/s; P<0.001) and Qmax was negatively correlated with obstruction grade (Spearman’s correlation coefficient −0.3, P<0.001), even when controlling for the negative correlation between age and Qmax (Spearman’s partial correlation coefficient −0.29, P<0.001). A threshold value of Qmax of 10 mL/s had a specificity of 70%, a positive predictive value (PPV) of 70% and a sensitivity of 47% for BOO. The specificity using a threshold Qmax of 15 mL/s was 38%, the PPV 67% and the sensitivity 82%. Those voiding <150 mL (n=225) had a 72% chance of BOO (overall prevalence of BOO 60%). In those voiding >150 mL the likelihood of BOO was 56%. The addition of a specific threshold of 10 mL/s to these higher volume voiders improved the PPV for BOO to 69%. Conclusion While uroflowmetry cannot replace pressure‐flow studies in the diagnosis of BOO, it can provide a valuable improvement over symptoms alone in the diagnosis of the cause of lower urinary tract dysfunction in men presenting with LUTS. This study provides performance statistics for Qmax with respect to BOO; such statistics may be used to define more accurately the presence or absence of BOO in men presenting with LUTS, so avoiding the need for formal pressure‐flow studies in everyday clinical practice, while improving the likelihood of a successful outcome from prostatectomy. This study also shows that low‐volume uroflowmetry can provide useful diagnostic information and that, as such, the data from such voids should not be discarded.
Manipulation of the gut microbiota presents a new opportunity to combat chronic diseases. Randomized controlled trials of probiotics suggest some associations with adiposity, lipids, and insulin resistance, but to our knowledge no trials with "hard" outcomes have been conducted. We used separate-sample Mendelian randomization to obtain estimates of the associations of 27 genera of gut microbiota with ischemic heart disease, type 2 diabetes mellitus, adiposity, lipid levels, and insulin resistance, based on summary data from CARDIoGRAAMplusC4D and other consortia. Among the 27 genera, a 1-allele increase in single nucleotide polymorphisms related to greater abundance of Bifidobacterium was associated with lower risk of ischemic heart disease (odds ratio = 0.985, 95% confidence interval (CI): 0.971, 1.000; P = 0.04), a 0.011-standard-deviation lower body mass index (95% CI: -0.017, -0.005), and a 0.026-standard-deviation higher low-density lipoprotein cholesterol level (95% CI: 0.019, 0.033), but the findings were not robust to exclusion of potential pleiotropy. We also identified Acidaminococcus, Aggregatibacter, Anaerostipes, Blautia, Desulfovibrio, Dorea, and Faecalibacterium as being nominally associated with type 2 diabetes mellitus or other risk factors. Results from our study indicate that these 8 genera of gut microbiota should be given priority in future research relating the gut microbiome to ischemic heart disease and its risk factors.
In the first 12 months after surgery transurethral prostatic incision has effectiveness that is equivalent to transurethral prostatic resection for treating patients with suspected benign prostatic obstruction who have a relatively small prostate. However, there is little evidence on the relative long-term effectiveness of the 2 treatments 2 to 5 or 10 years after surgery. There is no clear cutoff point for prostate size that leads to good results after transurethral prostatic incision. A large-scale, multicenter randomized controlled trial is now required to evaluate comprehensively the effectiveness, impact on quality of life and overall cost of transurethral prostatic incision compared with transurethral prostatic resection.
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