Trine Nielsen

University of Copenhagen

Pediatric obesity is a progressive, chronic disease that can lead to serious cardiometabolic complications. Here we investigated the peripheral lipidome in 958 children and adolescents with overweight or obesity and 373 with normal weight, in a cross-sectional study. We also implemented a family-based, personalized program to assess the effects of...

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 associ...

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, indi...

The microbiota in individual habitats differ both in relative composition and absolute abundance. While sequencing approaches determine only the relative abundances of taxa and genes, experimental techniques for absolute abundance determination are rarely applied to large-scale microbiome studies. Here, we developed a machine learning approach to p...

Background & aims: Genome-wide association studies have identified steatogenic variants that also showed pleiotropic effects on cardiometabolic traits in adults. We investigated the effect of eight previously reported genome-wide significant steatogenic variants, individually and combined in a weighted genetic risk score (GRS), on liver and cardio...

Background: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 di...

Background & aims: Alcohol disturbs hepatic lipid synthesis and transport, but the role of lipid dysfunction in alcohol-related liver disease (ALD) is unclear. In this biopsy-controlled, prospective, observational study, we characterized the liver and plasma lipidomes in patients with early ALD. Methods: We performed mass spectrometry-based lipi...

Objectives: The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased thrombotic and cardiovascular risks. Here we, sought to i) characterize which host variables contribute to fasting serum TMAO levels in real-life settings ii) identify potential actionable therapeutic means related to circulating TMAO. Design: We appl...

Background Schizophrenia (SCZ) is a heterogeneous neuropsychiatric disorder, for which current treatment has insufficient efficacy and severe adverse effects. The modifiable gut microbiome might be a potential target for intervention to improve neurobiological functions through the gut-microbiome-brain axis. Methods In this case-control study, gut...

Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and res...

Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the rol...

During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1,2,3,4,5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the ex...

Gut viruses are important, yet often neglected, players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies has been increasing; however, we are still only scratching the surface of the immense viral diversity. In this study, 254 virus-enriched fecal metagenomes from 204 Danish subjects were used to genera...

Background: Protein intake has been associated with the development of pre-diabetes (pre-T2D) and type 2 diabetes (T2D). The gut microbiota has the capacity to produce harmful metabolites derived from dietary protein. Furthermore, both the gut microbiota composition and metabolic status (e.g., insulin resistance) can be modulated by diet and ethni...

Background and aims Alcohol disturbs hepatic lipid synthesis and transport, but the role of lipid dysfunction in the severity of alcohol-related liver disease (ALD) is unclear. We therefore characterised the liver and plasma lipidome in a biopsy-controlled cohort of patients with early ALD. Methods We performed ultra-high-performance liquid chroma...

Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese...

Objective Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. Design In 271 middle-aged non-diabetic Danish individuals, who were stratified on...

Background: Gut viruses are important players in the complex human gut microbial ecosystem. Recently, the number of human gut virome studies is steadily increasing, however we are still only scratching the surface of the immense viral diversity as many wet lab and bio-informatics challenges remain. In this study, 254 virus-enriched faecal metagenom...

A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20412-9.

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propio...

Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childh...

Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low micro...

The chemical composition of feces plays an important role in human metabolism. Metabolomics and lipidomics are valuable tools for screening the metabolite composition in feces. Here we set out to describe fecal metabolite composition in healthy participants in frozen stools. Frozen stool samples were collected from 10 healthy volunteers and cryogen...

Introduction The chemical composition of feces plays an important role in human metabolism. Metabolomics and lipidomics are valuable tools for screening the metabolite composition in feces. Here we set out to describe fecal metabolite composition in healthy participants in frozen stools. Methods Frozen stool samples were collected from 10 healthy...

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 pri...

Recently, microRNAs (miRNAs) in circulating extracellular vesicles (EVs), have emerged as a source of potential biomarkers for various pathophysiological conditions, including metabolic disorders such as diabetes. Type 2 diabetes mellitus (T2DM), is the most prevalent form of diabetes in the USA, with 30 million diagnosed patients. Identifying miRN...

The liver and the gut closely interact as there is a bi-directional exchange of both microbial and host compounds between the two organs. In this chapter we will describe features of the gut-liver-axis and the impact of the bacterial microbiota on different stages of alcoholic and non-alcoholic (ALD, NAFLD) fatty liver diseases.

The human mouth provides a unique and heterogeneous habitat for a huge microbial community full of diversity and metabolic activity. Microbial representatives of all domains including, bacteria, fungi, archaea, protozoa, and viruses are forming a complex synergistic network which foundation is formed in our early childhood. The oral microbiota play...

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...

To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a...

We recently presented a three-pronged association study that integrated human intestinal microbiome data derived from shotgun-based sequencing with untargeted serum metabolome data and measures of host physiology. Metabolome and microbiome data are high dimensional, posing a major challenge for data integration. Here, we present a step-by-step comp...

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 54,65...

Background: Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum. Methods: Gut microbiota profiles of women with GDM (n = 50...

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 microbi...

Aims/hypothesis: Individuals with type 2 diabetes have aberrant intestinal microbiota. However, recent studies suggest that metformin alters the composition and functional potential of gut microbiota, thereby interfering with the diabetes-related microbial signatures. We tested whether specific gut microbiota profiles are associated with prediabet...

Introduction et but de l’etude Le but de l’etude europeenne MetaCardis est d’evaluer les relations qui existent entre les maladies cardiometaboliques et le microbiote intestinal. Sachant que l’alimentation module la composition du microbiote intestinal d’une part, et influe sur les risques de maladies cardiometaboliques d’autre part, les apports al...

Background: The European study MetaCardis aims to investigate the role of the gut microbiota in health and cardiometabolic diseases in France, Germany, and Denmark. To evaluate long-term diet-disease relationships, a food frequency questionnaire (FFQ) was found to be the most relevant dietary assessment method for the MetaCardis study. Objective:...

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect functional and metabolic interactions between cohabiting s...

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individuals is characterized by increased levels of branched...

Background Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated with obesity and some of its co-morbidities, like type 2...

Background The effects of probiotic supplementation on fecal microbiota composition in healthy adults have not been well established. We aimed to provide a systematic review of the potential evidence for an effect of probiotic supplementation on the composition of human fecal microbiota as assessed by high-throughput molecular approaches in randomi...

The exploration of the gut microbiota has intensified within the past decade with the introduction of cultivation-independent methods. By investigation of the gut bacterial genes, our understanding of the compositional and functional capability of the gut microbiome has increased. It is now widely recognized that the gut microbiota has profound eff...

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs on the microbiota, which may obscure microbial causes, prot...

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies in mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative...

Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly sequenced samples of the Metagenomics of the Human In...

Most current approaches for analyzing metagenomic data rely on comparisons to reference genomes, but the microbial diversity of many environments extends far beyond what is covered by reference databases. De novo segregation of complex metagenomic data into specific biological entities, such as particular bacterial strains or viruses, remains a lar...

doi:10.1038/nature09944 and corrigendum 474, 666 (2011); doi:10