Transmission and dynamics of mother-infant gut viruses during pregnancy and early life.

Early development of the gut ecosystem is crucial for lifelong health. While infant gut bacterial communities have been studied extensively, the infant gut virome remains under-explored. To study the development of the infant gut virome over time and the factors that shape it, we longitudinally assess the composition of gut viruses and their bacterial hosts in 30 women during and after pregnancy and in their 32 infants during their first year of life. Using shotgun metagenomic sequencing applied to dsDNA extracted from Virus-Like Particles (VLPs) and bacteria, we generate 205 VLP metaviromes and 322 total metagenomes. With this data, we show that while the maternal gut virome composition remains stable during late pregnancy and after birth, the infant gut virome is dynamic in the first year of life. Notably, infant gut viromes contain a higher abundance of active temperate phages compared to maternal gut viromes, which decreases over the first year of life. Moreover, we show that the feeding mode and place of delivery influence the gut virome composition of infants. Lastly, we provide evidence of co-transmission of viral and bacterial strains from mothers to infants, demonstrating that infants acquire some of their virome from their mother's gut.

Circulating miRNAs as Potential Biomarkers for Celiac Disease Development.

Background & Aims: Celiac disease (CeD), an immune-mediated disease with enteropathy triggered by gluten, affects ~1% of the general European population. Currently, there are no biomarkers to predict CeD development. MicroRNAs (miRNAs) are short RNAs involved in post-transcriptional gene regulation, and certain disease- and stage-specific miRNA profiles have been found previously. We aimed to investigate whether circulating miRNAs can predict the development of CeD. Methods: Using next-generation miRNA-sequencing, we determined miRNAs in >200 serum samples from 53 participants of the PreventCD study, of whom 33 developed CeD during follow-up. Following study inclusion at 3 months of age, samples were drawn at predefined ages, diagnosis (first anti-transglutaminase antibody (TGA) positivity or diagnostic biopsy) and after the start of a gluten-free diet (GFD). This allowed identification of circulating miRNAs that are deregulated before TGA positivity. For validation of the biomarkers for CeD and GFD response, two additional cohorts were included in subsequent meta-analyses. Additionally, miRNAs were measured in duodenal biopsies in a case-control cohort. Results: 53 circulating miRNAs were increased (27) or decreased (26) in CeD versus controls. We assessed specific trends in these individual miRNAs in the PreventCD cohort by grouping the pre-diagnostic samples of the CeD patients (all had negative TGA) by how close to seroconversion (first sample positive TGA) the samples were taken. 8/53 miRNAs differed significantly between controls and samples taken <1 year before TGA positivity: miR-21-3p, miR-374a-5p, 144-3p, miR-500a-3p, miR-486-3p let-7d-3p, let-7e-5p and miR-3605-3p. 6/26 downregulated miRNAs reconstituted upon GFD, including miR-150-5p/-3p, whereas no upregulated miRNAs were downregulated upon GFD. 15/53 biomarker candidates also differed between CeD biopsies and controls, with a concordant direction, indicating that these circulating miRNAs might originate from the intestine. Conclusions: We identified 53 circulating miRNAs that are potential early biomarkers for CeD, of which several can be detected more than a year before TGA positivity and some start to normalize upon GFD.

Lifelines COVID-19 cohort: investigating COVID-19 infection and its health and societal impacts in a Dutch population-based cohort.

PURPOSE: The Lifelines COVID-19 cohort was set up to assess the psychological and societal impacts of the COVID-19 pandemic and investigate potential risk factors for COVID-19 within the Lifelines prospective population cohort. PARTICIPANTS: Participants were recruited from the 140 000 eligible participants of Lifelines and the Lifelines NEXT birth cohort, who are all residents of the three northern provinces of the Netherlands. Participants filled out detailed questionnaires about their physical and mental health and experiences on a weekly basis starting in late March 2020, and the cohort consists of everyone who filled in at least one questionnaire in the first 8 weeks of the project. FINDINGS TO DATE: >71 000 unique participants responded to the questionnaires at least once during the first 8 weeks, with >22 000 participants responding to seven questionnaires. Compiled questionnaire results are continuously updated and shared with the public through the Corona Barometer website. Early results included a clear signal that younger people living alone were experiencing greater levels of loneliness due to lockdown, and subsequent results showed the easing of anxiety as lockdown was eased in June 2020. FUTURE PLANS: Questionnaires were sent on a (bi)weekly basis starting in March 2020 and on a monthly basis starting July 2020, with plans for new questionnaire rounds to continue through 2020 and early 2021. Questionnaire frequency can be increased again for subsequent waves of infections. Cohort data will be used to address how the COVID-19 pandemic developed in the northern provinces of the Netherlands, which environmental and genetic risk factors predict disease susceptibility and severity and the psychological and societal impacts of the crisis. Cohort data are linked to the extensive health, lifestyle and sociodemographic data held for these participants by Lifelines, a 30-year project that started in 2006, and to data about participants held in national databases.

Habitual dietary intake of IBD patients differs from population controls: a case-control study.

BACKGROUND: Since evidence-based dietary guidelines are lacking for IBD patients, they tend to follow "unguided" dietary habits; potentially leading to nutritional deficiencies and detrimental effects on disease course. Therefore, we compared dietary intake of IBD patients with controls. METHODS: Dietary intake of macronutrients and 25 food groups of 493 patients (207 UC, 286 CD), and 1291 controls was obtained via a food frequency questionnaire. RESULTS: 38.6% of patients in remission had protein intakes below the recommended 0.8 g/kg and 86.7% with active disease below the recommended 1.2 g/kg. Multinomial logistic regression, corrected for age, gender and BMI, showed that (compared to controls) UC patients consumed more meat and spreads, but less alcohol, breads, coffee and dairy; CD patients consumed more non-alcoholic drinks, potatoes, savoury snacks and sugar and sweets but less alcohol, dairy, nuts, pasta and prepared meals. Patients with active disease consumed more meat, soup and sugar and sweets but less alcohol, coffee, dairy, prepared meals and rice; patients in remission consumed more potatoes and spreads but less alcohol, breads, dairy, nuts, pasta and prepared meals. CONCLUSIONS: Patients avoiding potentially favourable foods and gourmandizing potentially unfavourable foods are of concern. Special attention is needed for protein intake in the treatment of these patients.

Lifelines NEXT: a prospective birth cohort adding the next generation to the three-generation Lifelines cohort study.

Epidemiological research has shown there to be a strong relationship between preconceptional, prenatal, birth and early-life factors and lifelong health. The Lifelines NEXT is a birth cohort designed to study the effects of intrinsic and extrinsic determinants on health and disease in a four-generation design. It is embedded within the Lifelines cohort study, a prospective three-generation population-based cohort study recording the health and health-related aspects of 167,729 individuals living in Northern Netherlands. In Lifelines NEXT we aim to include 1500 pregnant Lifelines participants and intensively follow them, their partners and their children until at least 1 year after birth. Longer-term follow-up of physical and psychological health will then be embedded following Lifelines procedures. During the Lifelines NEXT study period biomaterials-including maternal and neonatal (cord) blood, placental tissue, feces, breast milk, nasal swabs and urine-will be collected from the mother and child at 10 time points. We will also collect data on medical, social, lifestyle and environmental factors via questionnaires at 14 different time points and continuous data via connected devices. The extensive collection of different (bio)materials from mother and child during pregnancy and afterwards will provide the means to relate environmental factors including maternal and neonatal microbiome composition) to (epi)genetics, health and developmental outcomes. The nesting of the study within Lifelines enables us to include preconceptional transgenerational data and can be used to identify other extended families within the cohort.

Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome.

Changes in the gut microbiota have been associated with two of the most common gastrointestinal diseases, inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Here, we performed a case-control analysis using shotgun metagenomic sequencing of stool samples from 1792 individuals with IBD and IBS compared with control individuals in the general population. Despite substantial overlap between the gut microbiome of patients with IBD and IBS compared with control individuals, we were able to use gut microbiota composition differences to distinguish patients with IBD from those with IBS. By combining species-level profiles and strain-level profiles with bacterial growth rates, metabolic functions, antibiotic resistance, and virulence factor analyses, we identified key bacterial species that may be involved in two common gastrointestinal diseases.

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids.

RATIONALE: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. OBJECTIVES: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. METHODS AND RESULTS: We studied 893 subjects from the Life-Lines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤ 25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. CONCLUSIONS: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins.

Cohort profile: LifeLines DEEP, a prospective, general population cohort study in the northern Netherlands: study design and baseline characteristics.

PURPOSE: There is a critical need for population-based prospective cohort studies because they follow individuals before the onset of disease, allowing for studies that can identify biomarkers and disease-modifying effects, and thereby contributing to systems epidemiology. PARTICIPANTS: This paper describes the design and baseline characteristics of an intensively examined subpopulation of the LifeLines cohort in the Netherlands. In this unique subcohort, LifeLines DEEP, we included 1539 participants aged 18 years and older. FINDINGS TO DATE: We collected additional blood (n = 1387), exhaled air (n = 1425) and faecal samples (n = 1248), and elicited responses to gastrointestinal health questionnaires (n = 1176) for analysis of the genome, epigenome, transcriptome, microbiome, metabolome and other biological levels. Here, we provide an overview of the different data layers in LifeLines DEEP and present baseline characteristics of the study population including food intake and quality of life. We also describe how the LifeLines DEEP cohort allows for the detailed investigation of genetic, genomic and metabolic variation for a wide range of phenotypic outcomes. Finally, we examine the determinants of gastrointestinal health, an area of particular interest to us that can be addressed by LifeLines DEEP. FUTURE PLANS: We have established a cohort of which multiple data levels allow for the integrative analysis of populations for translation of this information into biomarkers for disease, and which will offer new insights into disease mechanisms and prevention.

Profile of volatile organic compounds in exhaled breath changes as a result of gluten-free diet.

In the present longitudinal study, we followed volatile organic compounds (VOCs) excreted in exhaled breath of 20 healthy individuals over time, while adhering to a gluten-free diet for 4 weeks prior to adherence to a normal diet. We used gas chromatography coupled with mass spectrometry (TD-GC-tof-MS) in combination with chemometric analysis to detect an array of VOCs in exhaled breath. Multivariate analysis was applied to extract the maximal information from the obtained data. Dietary intake was assessed to verify adherence to the diet and to get insight into macronutrient intake during the intervention period. A set of 12 volatile compounds distinguished the samples obtained during the gluten-free diet from those obtained during a normal diet. Seven compounds could be chemically identified (2-butanol, octane, 2-propyl-1pentanol, nonanal, dihydro-4-methyl-2(3H)-furanone, nonanoic acid and dodecanal) and speculated on a possible origin. Our findings suggest that a gluten-free dietary period had a reversible impact on participants' excreted metabolites visible in their breath. Several explanations are proposed of influencing metabolic status through dietary interventions. Although the exact origin of the discriminating compounds is not yet known, the main goal of this paper was to share a new potential use of exhaled air analysis and might become a useful tool in fields of nutrition and metabolism.