Aims/hypothesis
Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by ...medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment.
Methods
Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6 weeks. Inclusion criteria were men of age 18–35 years, BMI between 18.5 kg/m
2
and 27.5 kg/m
2
, HbA
1c
< 39 mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2 months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1 g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit.
Results
Data from participants who completed visit 1 (
n
=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of
Intestinibacter
spp. and
Clostridium
spp., as well as an increased abundance of
Escherichia/Shigella
spp. and
Bilophila wadsworthia
. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects.
Conclusions/interpretation
Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies.
Trial registration
Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050
Funding
This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation
Replacing traditional internal combustion engine vehicles with electric vehicles (EVs) proves to be challenging for the transport sector, particularly due to the higher initial investment. As EVs ...could be more profitable by participating in the electricity markets, the aim of this paper is to investigate revenue potentials when marketing bidirectionally chargeable electric vehicles in the spot market. To simulate a realistic marketing behavior of electric vehicles, a mixed integer linear, rolling horizon optimization model is formulated considering real trading times in the day-ahead and intraday market. Results suggest that revenue potentials are strongly dependent on the EV pool, the user behavior and the regulatory framework. Modeled potential revenues of EVs of current average size marketed with 2019 German day-ahead prices are found to be at around 200 €/EV/a, which is comparable to other findings in literature, and go up to 500 €/EV/a for consecutive trading in German day-ahead and intraday markets. For future EVs with larger batteries and higher efficiencies, potential revenues for current market prices can reach up to 1300 €/EV/a. This study finds that revenues differ widely for different European countries and future perspectives. The identified revenues give EV owners a clear incentive to participate in vehicle-to-grid use cases, thereby increasing much needed flexibility for the energy system of the future.
Intelligent, bidirectional charging strategies (vehicle-to-X, V2X) are a crucial part of the decarbonization of the transport sector. To facilitate the successful rollout of business models ...associated with V2X, we identify revenue potentials for different use cases, additional costs, and resulting profits for future years. Our assessments result in ranges of profits for different V2X types with the spread of profits providing a measure of uncertainty. The profit analysis shows that some V2X types can most certainly become profitable in the near future. For vehicle-to-home (V2H), for instance, profits of 390 € per vehicle and year in 2040 are determined, if viewed optimistically. Other V2X types (vehicle-to-business, V2B, and vehicle-to-grid, V2G) are subject to high uncertainties, where high as well as low or no profits are possible for future years. External circumstances are found to be of great impact regarding V2X profitability with user type and location being most relevant. Based on this, we derive business model implications and draw conclusions for a well-considered business model design. To mitigate uncertainties and increase the change of profitability, the focus of business model development should be on customer segments, revenue streams and value propositions.
In addition to a massive expansion of renewable energies, a successful change towards a decarbonized energy system requires the flexibilization of consumers and the integration of storage and sector ...coupling technologies. Bidirectionally chargeable electric vehicles (EVs) represent such a consumer flexibility. They are able to charge when there is an electricity generation surplus and to discharge when there is a shortage in electricity generation. Therefore, they can act as a storage from the perspective of the energy system. This paper analyzes different modeling approaches of bidirectionally chargeable EVs in large-scale energy systems and evaluates the impact of bidirectionally chargeable EVs on the future European energy system design. We compare the modeling of discrete EV profiles, clustered EV profiles as well as an aggregated EV profile with simplified constraints. Aggregation of EV profiles per country leads to significantly lower computation times, while still achieving results close to the reference case. The number of bidirectionally chargeable EVs in a cost optimal future European energy system increases from 6 million EVs in 2025 to over 60 million EVs in 2050. We show that bidirectionally chargeable EVs lead to a better integration of PV generation, to lower installed capacities of gas- and hydrogen-fired power plants as well as stationary battery storages. They also lead to decreasing electricity prices and total European energy system costs.
Little is known about the effect of long-term diet patterns on the composition and functional potential of the human salivary microbiota. In the present study, we sought to contribute to the ongoing ...elucidation of dietary effects on the oral microbial community by examining the diversity, composition and functional potential of the salivary microbiota in 160 healthy vegans and omnivores using 16S rRNA gene amplicon sequencing. We further sought to identify bacterial taxa in saliva associated with host inflammatory markers. We show that compositional differences in the salivary microbiota of vegans and omnivores is present at all taxonomic levels below phylum level and includes upper respiratory tract commensals (e.g. Neisseria subflava, Haemophilus parainfluenzae, and Rothia mucilaginosa) and species associated with periodontal disease (e.g. Campylobacter rectus and Porphyromonas endodontalis). Dietary intake of medium chain fatty acids, piscine mono- and polyunsaturated fatty acids, and dietary fibre was associated with bacterial diversity, community structure, as well as relative abundance of several species-level operational taxonomic units. Analysis of imputed genomic potential revealed several metabolic pathways differentially abundant in vegans and omnivores indicating possible effects of macro- and micro-nutrient intake. We also show that certain oral bacteria are associated with the systemic inflammatory state of the host.
We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a ...splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.
The shift to electric transportation is crucial to fighting climate change. However, Germany’s goal of 15 million electric vehicles (EVs) by 2030 remains distant. Therefore, enhancing their economic ...viability is essential to promoting EV adoption. One promising option to increase the economics for the user is PV self-consumption optimization using smart charging EVs. Yet, more research is needed to explore the use case’s impacts on the German/European energy systems. Therefore, PV self-consumption optimization using EVs is integrated into an energy system model, assessing its impact on the energy system in 2030. For this purpose, the use case is modeled for different groups of people—personas—which are defined in a way that creates a diverse set of personas reflecting the distribution of different statistical values within Germany. The modified (dis)charging profiles are then aggregated and integrated into the energy system model. With a high implementation of PV self-consumption optimization in Germany in 2030, a positive system effect (with a system cost reduction of 53 million EUR/a) can be observed with a lower need for further storage and less curtailment of renewable energies (RES). Furthermore, the market values for RES increase by 0.7%, which fosters the integration of RES.
Abstract The microbial communities of the oral cavity are important elements of oral and systemic health. With emerging evidence highlighting the heritability of oral bacterial microbiota, this study ...aimed to identify host genome variants that influence oral microbial traits. Using data from 16S rRNA gene amplicon sequencing, we performed genome-wide association studies with univariate and multivariate traits of the salivary microbiota from 610 unrelated adults from the Danish ADDITION-PRO cohort. We identified six single nucleotide polymorphisms (SNPs) in human genomes that showed associations with abundance of bacterial taxa at different taxonomical tiers ( P < 5 × 10 –8 ). Notably, SNP rs17793860 surpassed our study-wide significance threshold ( P < 1.19 × 10 –9 ). Additionally, rs4530093 was linked to bacterial beta diversity ( P < 5 × 10 –8 ). Out of these seven SNPs identified, six exerted effects on metabolic traits, including glycated hemoglobin A1c, triglyceride and high-density lipoprotein cholesterol levels, the risk of type 2 diabetes and stroke. Our findings highlight the impact of specific host SNPs on the composition and diversity of the oral bacterial community. Importantly, our results indicate an intricate interplay between host genetics, the oral microbiota, and metabolic health. We emphasize the need for integrative approaches considering genetic, microbial, and metabolic factors.
Latent autoimmune diabetes in adults (LADA) is a heterogeneous disease characterized by autoantibodies against insulin producing pancreatic beta cells and initial lack of need for insulin treatment. ...The aim of the present study was to investigate if individuals with LADA have an altered gut microbiota relative to non-diabetic control subjects, individuals with type 1 diabetes (T1D), and individuals with type 2 diabetes (T2D). Bacterial community profiling was performed with primers targeting the variable region 4 of the 16S rRNA gene and sequenced. Amplicon sequence variants (ASVs) were generated with DADA2 and annotated to the SILVA database. The gut virome was sequenced, using a viral particle enrichment and metagenomics approach, assembled, and quantified to describe the composition of the viral community. Comparison of the bacterial alpha- and beta-diversity measures revealed that the gut bacteriome of individuals with LADA resembled that of individuals with T2D. Yet, specific genera were found to differ in abundance in individuals with LADA compared with T1D and T2D, indicating that LADA has unique taxonomical features. The virome composition reflected the stability of the most dominant order Caudovirales and the families Siphoviridae, Podoviridae, and Inoviridae, and the dominant family Microviridae. Further studies are needed to confirm these findings.
Introduction
Previous research indicates that the salivary microbiota may be a biomarker of oral as well as systemic disease. However, clarifying the potential bias from general health status and ...lifestyle-associated factors is a prerequisite of using the salivary microbiota for screening.
Materials & Methods
ADDDITION-PRO is a nationwide Danish cohort, nested within the Danish arm of the Anglo-Danish-Dutch Study of Intensive treatment in People with Screen-Detected Diabetes in Primary Care. Saliva samples from n=746 individuals from the ADDITION-PRO cohort were characterized using 16s rRNA sequencing. Alpha- and beta diversity as well as relative abundance of genera was examined in relation to general health and lifestyle-associated variables. Permutational multivariate analysis of variance (PERMANOVA) was performed on individual variables and all variables together. Classification models were created using sparse partial-least squares discriminant analysis (sPLSDA) for variables that showed statistically significant differences based on PERMANOVA analysis (p < 0.05).
Results
Glycemic status, hemoglobin-A
1c
(HbA
1c
) level, sex, smoking and weekly alcohol intake were found to be significantly associated with salivary microbial composition (individual variables PERMANOVA, p < 0.05). Collectively, these variables were associated with approximately 5.8% of the observed differences in the composition of the salivary microbiota. Smoking status was associated with 3.3% of observed difference, and smoking could be detected with good accuracy based on salivary microbial composition (AUC 0.95, correct classification rate 79.6%).
Conclusions
Glycemic status, HbA
1c
level, sex, smoking and weekly alcohol intake were significantly associated with the composition of the salivary microbiota. Despite smoking only being associated with 3.3% of the difference in overall salivary microbial composition, it was possible to create a model for detection of smoking status with a high correct classification rate. However, the lack of information on the oral health status of participants serves as a limitation in the present study. Further studies in other cohorts are needed to validate the external validity of these findings.
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