The effect of drinking water pH on the human gut microbiota and glucose regulation:results of a randomized controlled cross-over intervention

Abstract Studies in rodent models have shown that alterations in drinking water pH affect both the composition of the gut microbiota and host glucose regulation. To explore a potential impact of electrochemically reduced alkaline (pH ≈ 9) versus neutral (pH ≈ 7) drinking water (2 L/day) on human intestinal microbiota and host glucose metabolism we conducted a randomized, non-blinded, cross-over study (two 2-week intervention periods, separated by a 3-week wash-out) in 29 healthy, non-smoking Danish men, aged 18 to 35 years, with a body mass index between 20.0 to 27.0 kg m-2. Volunteers were ineligible if they had previously had abdominal surgery, had not been weight stabile for at least two months, had received antibiotic treatment within 2 months, or had a habitual consumption of caloric or artificially sweetened beverages in excess of 1 L/week or an average intake of alcohol in excess of 7 units/week. Microbial DNA was extracted from faecal samples collected at four time points, before and after each intervention, and subjected to 16S rRNA gene amplicon sequencing (Illumina MiSeq, V4 region). Glycaemic regulation was evaluated by means of an oral glucose tolerance test.No differential effect of alkaline versus neutral drinking water was observed for the primary outcome, overall gut microbiota diversity as represented by Shannon’s index. Similarly, neither a differential effect on microbiota richness or community structure was observed. Nor did we observe a differential effect on the abundance of individual operational taxonomic units (OTUs) or genera. However, analyses of within period effects revealed a significant (false discovery rate ≤5%) increase in the relative abundance of 9 OTUs assigned to order Clostridiales, family Ruminococcaceae, genus Bacteroides, and species Prevotella copri, indicating a potential effect of quantitative or qualitative changes in habitual drinking habits. An increase in the concentration of plasma glucose at 30 minutes and the incremental area under the curve of plasma glucose from 0 30 and 0 120 minutes, respectively, was observed when comparing the alkaline to the neutral intervention. However, results did not withstand correction for multiplicity. In contrast to what has been reported in rodents, a change in drinking water pH had no impact on the composition of the gut microbiota or glucose regulation in young male adults. The study is registered at www.clinicaltrials.gov (NCT02917616)

Intake of macro- and micronutrients in Danish vegans

BACKGROUND: Since information about macro- and micronutrient intake among vegans is limited we aimed to determine and evaluate their dietary and supplementary intake. METHODS: Seventy 18–61 years old Danish vegans completed a four-day weighed food record from which their daily intake of macro- and micronutrients was assessed and subsequently compared to an age-range-matched group of 1 257 omnivorous individuals from the general Danish population. Moreover, the vegan dietary and supplementary intake was compared to the 2012 Nordic Nutrition Recommendations (NNR). RESULTS: Dietary intake differed significantly between vegans and the general Danish population in all measured macro- and micronutrients (p < 0.05), except for energy intake among women and intake of carbohydrates among men. For vegans the intake of macro- and micronutrients (including supplements) did not reach the NNR for protein, vitamin D, iodine and selenium. Among vegan women vitamin A intake also failed to reach the recommendations. With reference to the NNR, the dietary content of added sugar, sodium and fatty acids, including the ratio of PUFA to SFA, was more favorable among vegans. CONCLUSIONS: At the macronutrient level, the diet of Danish vegans is in better accordance with the NNR than the diet of the general Danish population. At the micronutrient level, considering both diet and supplements, the vegan diet falls short in certain nutrients, suggesting a need for greater attention toward ensuring recommended daily intake of specific vitamins and minerals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12937-015-0103-3) contains supplementary material, which is available to authorized users

A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults

\ua9 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Population-based studies of relationships between dietary acidity load, insulin resistance and incident diabetes in Danes 11 Medical and Health Sciences 1103 Clinical Sciences

Abstract Background It has been suggested that the acidity of the diet may be related to increased risk of type 2 diabetes. To investigate this hypothesis, we tested if the acidity of the diet, measured as the Potential Renal Acid Load (PRAL) score, was associated with incident diabetes and diabetes-related intermediary traits. Methods A total of 54,651 individuals from the Danish Diet, Cancer and Health (DCH) cohort were included in the prospective cox regression analyses of incident diabetes over a 15 years follow-up period. Moreover, 5724 Danish individuals with baseline data from the Inter99 cohort were included in the cross sectional, multivariate and logistic regression analyses of measures of insulin sensitivity, insulin release and glucose tolerance status derived from an oral glucose tolerance test (OGTT). Results In the DCH cohort a trend analysis showed that quintiles of PRAL score were, after multifactorial adjustment, associated with a higher incidence of diabetes (p trend = 6 × 10− 7). HR for incident diabetes was 1.24 (1.14; 1.35) (p = 7 × 10− 7) between first and fifth PRAL score quintile. In Inter99 higher PRAL score associated with insulin resistance as estimated by lower BIGTT-Si (an OGTT-derived index of insulin sensitivity) (p = 4 × 10− 7) and Matsuda index of insulin sensitivity (p = 2 × 10− 5) as well as higher HOMA-IR (p = 0.001). No association was observed for measures of insulin release, but higher PRAL score was associated with lower OGTT-based disposition index. Conclusions A high dietary acidity load is associated with a higher risk of diabetes among middle-aged Danes. Although adjustment for BMI attenuated the effect sizes the association remained significant. The increased risk of diabetes may be related to our finding that a high dietary acidity load associates with impaired insulin sensitivity

National Implementation of Simulator Training Improves Transurethral Resection of Bladder Tumours in Patients

BACKGROUND: Transurethral resection of bladder tumours (TURBT) is the initial diagnostic treatment for patients with bladder cancer. TURBT is not an easy procedure to master and simulator training may play a role in improving the learning curve. OBJECTIVE: To implement a national training programme for simulation-based mastery learning in TURBT and explore operating theatre performance after training. DESIGN, SETTING, AND PARTICIPANTS: From June 2019 to March 2021, 31 doctors at urology departments in Denmark performed two pretraining TURBT procedures on patients, followed by proficiency-based mastery learning on a virtual reality simulator and then two post-training TURBTs on patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Operating theatre performances were video-recorded and assessed by two independent, blinded raters using the Objective Structured Assessment for Transurethral Resection of Bladder Tumours Skills (OSATURBS) assessment tool. Paired-sample t tests were used to compare pretraining and post-training analyses and independent t tests for between-group comparisons. This trial is registered at ClinicalTrials.gov as NCT03864302. RESULTS AND LIMITATIONS: Before training, novices had significantly lower performance scores in comparison to those with intermediate experience (p = 0.017) and experienced doctors (p < 0.001). After training, novices significantly improved their clinical performance score (from 11.4 to 17.1; p = 0.049, n = 10). Those with intermediate experience and experienced doctors did not benefit significantly from simulator training (p = 0.9 and p = 0.8, respectively). CONCLUSIONS: Novices improved their TURBT performance in the operating theatre after completing a proficiency-based training programme on a virtual reality simulator. PATIENT SUMMARY: We trained surgeons in an operation to remove bladder tumours using a virtual reality simulator. Novice doctors improved their performance significantly after the training, but the training effects for more experienced doctors were minimal. Therefore, we suggest the introduction of mandatory simulator training in the residency programme for urologists