Publications
2026
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Gut microbiome maturation in early childhood interacts with host genetics to predict type 1 diabetes risk
Prospective evidence linking early-life microbiome development and host genetics with type 1 diabetes (T1D) risk is limited. Here, we describe how gut microbiome maturation and host genetics influence T1D risk in the TEDDY study. We analysed 12,151 longitudinal metagenomes and host genetic data from 887 children at high genetic risk for T1D followed for up to 6 years. We identify three microbiome maturational patterns: Early Matured, Late Matured and Early Plateaued, driven primarily by... -
Wastewater viromics reveals host-structured viral signals and non-human pathogens
Wastewater represents a powerful platform for human virus surveillance. However, the entry of animal- and plant-associated viruses into sewage is heterogeneous and incompletely understood, creating uncertainty about how reliably wastewater reflects non-human virus circulation. Here, we address this by analysing monthly wastewater metagenomic data from two distinct periods (2020-2021 and 2024-2025) across five major Finnish wastewater treatment plant catchments using a targeted hybrid-capture... -
Maternal Intake of Vitamins A, C, D, and E During Pregnancy and Risk of Type 1 Diabetes in the Child: The Norwegian Mother, Father, and Child Cohort Study
CONCLUSIONS: This prospective cohort study does not support the hypothesis that higher maternal intake of vitamins A, C, D, and E during pregnancy would decrease risk of type 1 diabetes in the child. Corroborated with previous evidence, our findings support a general pattern of null associations. -
Safety and Immunogenicity of a Vaccine Against Coxsackieviruses B (PRV-101)-Follow-up of the First-in-Human Phase 1 Trial
CONCLUSIONS: These results suggest that PRV-101 induces durable antibody responses lasting for at least 2 years. The findings support the continued development of PRV-101 for preventing both acute coxsackie B virus infections and chronic diseases like type 1 diabetes and celiac disease. -
Early-life immunological and microbial differences between East African and North European children
CONCLUSIONS: These results highlight the early emergence of differences in the immune system and gut microbiota between children living in extremities of the microbial exposure gradient. These differences add to the existing knowledge of possible factors contributing to increasing prevalence of chronic inflammatory diseases in African societies shifting towards more Westernized lifestyle. -
Comparative core-genome MLST of vancomycin-resistant Enterococcus faecium supports the utility of wastewater-based surveillance: a pilot study
Wastewater-based surveillance (WBS) could complement clinical data and be used as an early warning tool for population-level monitoring of priority pathogens such as vancomycin-resistant Enterococcus faecium (VREfm). In this pilot study, we isolated VREfm using CHROMAgar VRE from 77 composite wastewater influent samples from ten wastewater treatment plants (WWTPs), assessed their phenotypic antibiotic susceptibility profiles using the broth microdilution assay, and used core genome MLST (cgMLST)...
2025
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The Contribution of BMI to a Young Child's Risk of Islet Autoimmunity Is Dependent on HLA-DR4-DQ8 Without HLA-DR3-DQ2
CONCLUSIONS: The contribution of BMI to risk of IA during early childhood is dependent on the HLA-DR-DQ genotype more so than the first-appearing IA phenotype. -
Machine learning-based identification of wastewater treatment plant-specific microbial indicators using 16S rRNA gene sequencing
Effluent released from municipal wastewater treatment plants reflects the microbial communities responsible for degrading and removing contaminants within the plants. Monitoring this effluent offers essential insights into its environmental impacts, the efficiency of treatment processes, and the presence of emerging contaminants. To support improved monitoring and source attribution, our study employed a machine-learning framework to identify microbial indicators capable of distinguishing... -
Development of an online portal for wastewater-based surveillance of multiple pathogens - A WastPan Study
Microbes represent a significant disease burden and can cause widespread pandemics resulting in substantial challenges to public health and economic losses. Traditionally, Finland's epidemic surveillance has been based on hospital diagnoses and their reporting to the National Infectious Diseases Register. During the SARS-CoV-2 pandemic, wastewater-based surveillance (WBS) emerged as a cost-effective method in Finland and globally, offering surveillance data without requiring clinical diagnoses... -
Antibodies against <em>Clostridium butyricum</em> in the children of mothers at risk for gestational diabetes
Gestational diabetes mellitus (GDM) is linked to an imbalance in gut microbiota composition, which can be transferred to the mother's offspring. Clostridium butyricum, known for its health benefits in diabetes and allergy, lacks sufficient data regarding its effect on the immune system's development in the offspring of mothers with GDM. This study assessed antibody responses against C. butyricum T2F3 in children of mothers at risk for GDM, involving 88 children aged 1-6 years. Antibody responses... -
Virus detection in influent, activated sludge, and effluent from municipal wastewater treatment plants using composite and grab samples in Finland
Wastewater-based surveillance has been commonly used as a monitoring tool for public health. Also, viruses present in wastewater can pose a health risk. In this study, we screened enterovirus, rhinovirus, norovirus GI and GII, pan-adenovirus, and gastroenteritis-causing adenovirus F40/41 in different wastewater sample types using reverse transcription quantitative polymerase chain reaction and quantitative polymerase chain reaction. We analyzed composite influent samples (N = 22), grab influent... -
Unfolding the Mystery of Autoimmunity: The Environmental Determinants of Diabetes in the Young (TEDDY) Study
In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac... -
Immunological and structural evaluation of the intranasally administrated CVB1 whole-virus and VLP vaccines
Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, cardiomyopathy, and meningitis. CVBs replicate in mucosal membranes. Therefore, vaccines inducing robust mucosal immune responses are needed. We investigated the immunogenicity of virus-like particles (VLP) and inactivated virus vaccines for CVB1, administered to mice either subcutaneously or intranasally, formulated with and without commercial and an experimental adjuvant. In this study, epigallocatechin-3-gallate... -
Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes
CONCLUSIONS/INTERPRETATION: This was the largest coordinated effort to examine the presence of enterovirus RNA in the pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that donors with type 1 diabetes and donors with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues. -
Wastewater based genomic surveillance key to population level monitoring of AmpC/ESBL producing Escherichia coli
Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we leverage the power of whole genome sequencing (WGS) to screen AmpC- and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli from 77 composite samples obtained from 10 wastewater treatment plants across Finland. We found a high abundance of multidrug-resistant AmpC/ESBL-producing E. coli and significant differences... -
Early Appearance of Thyroid Autoimmunity in Children Followed From Birth for Type 1 Diabetes Risk
CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypothyroidism or hyperthyroidism.
2024
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Risk of celiac disease autoimmunity is modified by interactions between CD247 and environmental exposures
Season of birth, viral infections, HLA haplogenotypes and non-HLA variants are implicated in the development of celiac disease and celiac disease autoimmunity, suggesting a combined role of genes and environmental exposures. The aim of the study was to further decipher the biological pathways conveying the season of birth effect in celiac disease autoimmunity to gain novel insights into the early pathogenesis of celiac disease. Interactions between season of birth, genetics, and early-life... -
Detection of enterovirus RNA in pancreas and lymphoid tissues of organ donors with type 1 diabetes
CONCLUSIONS/INTERPRETATION: This was the largest coordinated effort to examine the presence of enterovirus RNA in pancreas of organ donors with type 1 diabetes, using a multitude of assays. These findings are consistent with the notion that both the subjects with type 1 diabetes and those with islet autoantibodies may carry a low-grade enterovirus infection in the pancreas and lymphoid tissues. -
Production, analysis, and safety assessment of a soil and plant-based natural material with microbiome- and immune-modulatory effects
It has been suggested that reduced contact with microbiota from the natural environment contributes to the rising incidence of immune-mediated inflammatory disorders (IMIDs) in western, highly urbanized societies. In line with this, we have previously shown that exposure to environmental microbiota in the form of a blend comprising of soil and plant-based material (biodiversity blend; BDB) enhances the diversity of human commensal microbiota and promotes immunoregulation that may be associated... -
Characterization of methicillin resistant <em>Staphylococcus Aureus</em> in municipal wastewater in Finland
Wastewater-based surveillance (WBS) of multidrug-resistant bacteria could complement clinical data, serving as a population-level early warning tool. This study evaluated WBS as a pandemic preparedness tool, by selectively isolating and culturing methicillin-resistant Staphylococcus aureus (MRSA) with CHROMagar MRSA. Some 24-h composite wastewater samples (n = 80) were collected from ten treatment plants across Finland between February 2021 and January 2022. MRSA prevalence in wastewater samples... -
Simultaneous biomass concentration and subsequent quantitation of multiple infectious disease agents and antimicrobial resistance genes from community wastewater
Wastewater-based surveillance (WBS) of infectious disease agents is increasingly seen as a reliable source of population health data. To date, wastewater-based surveillance efforts have largely focused on individual pathogens. However, given that wastewater contains a broad range of pathogens circulating in the population, a more comprehensive approach could enhance its usability. We focused on the simultaneous detection of SARS-CoV-2, sapovirus, Campylobacter jejuni, Campylobacter coli,... -
Comparison of Different Reverse Transcriptase-Polymerase Chain Reaction-Based Methods for Wastewater Surveillance of SARS-CoV-2: Exploratory Study
CONCLUSIONS: As our study, as well as most of the previous studies, has shown RT-ddPCR to be more sensitive than RT-qPCR, its use in the wastewater surveillance of SARS-CoV-2 should be considered, especially if the amount of SARS-CoV-2 circulating in the population was low. All the analysis steps must be optimized for wastewater surveillance as our study showed that all the analysis steps including the compatibility of the RNA extraction, the RT-PCR kit, and the target gene assay influence the... -
Skin exposure to soil microbiota elicits changes in cell-mediated immunity to pneumococcal vaccine
A resilient immune system is characterized by its capacity to respond appropriately to challenges, such as infections, and it is crucial in vaccine response. Here we report a paired randomized intervention-control trial in which we evaluated the effect of microbially rich soil on immune resilience and pneumococcal vaccine response. Twenty-five age and sex matched pairs of volunteers were randomized to intervention and control groups. The intervention group rubbed hands three times a day in... -
Comparison of structure and immunogenicity of CVB1-VLP and inactivated CVB1 vaccine candidates
Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, dilated cardiomyopathy and aseptic meningitis. However, no CVB-vaccines are available for human use. In this study, we investigated the immunogenicity of virus-like particle (VLP) and inactivated whole-virus vaccines for CVB1 when administrated to mice via either subcutaneous or intranasal routes formulated with and without commercial and experimental adjuvants. Here, the potential of utilizing... -
Maternal gluten, cereal, and dietary fiber intake during pregnancy and lactation and the risk of islet autoimmunity and type 1 diabetes in the child
CONCLUSIONS: We observed no association between maternal intake of gluten, most consumed cereals, or dietary fiber during pregnancy or lactation and the risk of islet autoimmunity or type 1 diabetes in children from a high-risk population. -
Wastewater-based surveillance is an efficient monitoring tool for tracking influenza A in the community
Around the world, influenza A virus has caused severe pandemics, and the risk of future pandemics remains high. Currently, influenza A virus surveillance is based on the clinical diagnosis and reporting of disease cases. In this study, we apply wastewater-based surveillance to monitor the amount of the influenza A virus RNA at the population level. We report the influenza A virus RNA levels in 10 wastewater treatment plant catchment areas covering 40 % of the Finnish population. Altogether, 251... -
Detection of SARS-COV-2 variants and their proportions in wastewater samples using next-generation sequencing in Finland
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants may have different characteristics, e.g., in transmission, mortality, and the effectiveness of vaccines, indicating the importance of variant detection at the population level. Wastewater-based surveillance of SARS-CoV-2 RNA fragments has been shown to be an effective way to monitor the COVID-19 pandemic at the population level. Wastewater is a complex sample matrix affected by environmental factors and PCR inhibitors, causing... -
Developing wastewater-based surveillance schemes for multiple pathogens: The WastPan project in Finland
Wastewater comprises multiple pathogens and offers a potential for wastewater-based surveillance (WBS) to track the prevalence of communicable diseases. The Finnish WastPan project aimed to establish wastewater-based pandemic preparedness for multiple pathogens (viruses, bacteria, parasites, fungi), including antimicrobial resistance (AMR). This article outlines WastPan's experiences in this project, including the criteria for target selection, sampling locations, frequency, analysis methods,... -
Intake of B vitamins and the risk of developing islet autoimmunity and type 1 diabetes in the TEDDY study
PURPOSE: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years. -
Safety, tolerability and immunogenicity of PRV-101, a multivalent vaccine targeting coxsackie B viruses (CVBs) associated with type 1 diabetes: a double-blind randomised placebo-controlled Phase I trial
CONCLUSIONS/INTERPRETATION: The results indicate that the tested multivalent CVB vaccine is well tolerated and immunogenic, supporting its further clinical development. -
Clinically relevant sequence types of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae detected in Finnish wastewater in 2021-2022
CONCLUSIONS: Our study highlights the presence of clinically relevant strains of CP E. coli and K. pneumoniae in community wastewater. The results indicate that wastewater surveillance could serve as a monitoring tool for CP Enterobacterales. However, the specificity and sensitivity of the methods should be improved, and technologies, like advanced sequencing methods, should be utilized to distinguish data with public health relevance, harness the full potential of wastewater surveillance, and...
2023
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Distinct transcriptomic profiles in children prior to the appearance of type 1 diabetes-linked islet autoantibodies and following enterovirus infection
Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific... -
Gastrointestinal Infections Modulate the Risk for Insulin Autoantibodies as the First-Appearing Autoantibody in the TEDDY Study
CONCLUSIONS: Bidirectional associations were observed. GIEs were associated with increased IAA risk when reported before 1 year of age or 12-23 months prior to IAA. Norwalk virus was identified as one possible candidate factor. GIEs reported during the 2nd year of life were associated with a decreased IAA risk. -
HLA Genotype and Probiotics Modify the Association Between Timing of Solid Food Introduction and Islet Autoimmunity in the TEDDY Study
CONCLUSIONS: Timing of solid food introduction, including rice, may be associated with IA in children with the HLA DR3/4 genotype not exposed to probiotics. The microbiome composition under these exposure combinations requires further study. -
SARS-CoV-2 - No Increased Islet Autoimmunity or Type 1 Diabetes in Teens
No abstract -
Genomic epidemiology of nosocomial carbapenemase-producing <em>Citrobacter freundii</em> in sewerage systems in the Helsinki metropolitan area, Finland
Multi-drug resistance is emerging in Citrobacter freundii, which is the third most common carbapenemase-producing (CP) Enterobacteriaceae in humans in Finland due to recent outbreaks. The objective of this study was to determine if wastewater surveillance (WWS) could detect CP C. freundii strains causing infections in humans. Selective culturing was used to isolate CP C. freundii from the hospital environment, hospital wastewater, and untreated municipal wastewater in Helsinki, Finland, between... -
Physical Activity and the Development of Islet Autoimmunity and Type 1 Diabetes in 5- to 15-Year-Old Children Followed in the TEDDY Study
CONCLUSIONS: More daily minutes spent in moderate to vigorous physical activity was associated with a reduced risk of progression to type 1 diabetes in children aged 5-15 years who had developed multiple IAs. -
Skin, gut, and sand metagenomic data on placebo-controlled sandbox biodiversity intervention study
The metagenomic data presented in this article are related to the published research of "A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children" This database contains 16S ribosomal RNA (rRNA) metagenomics of sandbox sand and skin and gut microbiota of children in the intervention and placebo daycares. In intervention daycares, children... -
Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload: Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes. -
Monkeypox outbreak: Wastewater and environmental surveillance perspective
Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no... -
Association between asymptomatic infections and linear growth in 18-24-month-old Malawian children
Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to length-for-age Z-score (LAZ) at 24 months by constructing an interconnected network of various infections, biomarkers of inflammation (as assessed by...
2022
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Wastewater surveillance of antibiotic-resistant bacterial pathogens: A systematic review
Infectious diseases caused by antibiotic-resistant bacterial (ARB) pathogens are a serious threat to human and animal health. The active surveillance of ARB using an integrated one-health approach can help to reduce the emergence and spread of ARB, reduce the associated economic impact, and guide antimicrobial stewardship programs. Wastewater surveillance (WWS) of ARB provides composite samples for a total population, with easy access to the mixed community microbiome. This concept is emerging... -
Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism
The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related... -
Monkeypox outbreak: Wastewater and environmental surveillance perspective
Monkeypox disease (MPXD), a viral disease caused by the monkeypox virus (MPXV), is an emerging zoonotic disease endemic in some countries of Central and Western Africa but seldom reported outside the affected region. Since May 2022, MPXD has been reported at least in 74 countries globally, prompting the World Health Organization to declare the MPXD outbreak a Public Health Emergency of International Concern. As of July 24, 2022; 92 % (68/74) of the countries with reported MPXD cases had no... -
Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study
CONCLUSIONS: Predictors of IAA-first versus GADA-first autoimmunity differ from each other and from the predictors of progression to diabetes. -
Rising Hemoglobin A1c in the Nondiabetic Range Predicts Progression of Type 1 Diabetes As Well As Oral Glucose Tolerance Tests
CONCLUSIONS: An increase of ≥10% in HbA1c from baseline is as informative as OGTT 2-hPG in predicting risk of stage 3 in youth with genetic risk and diabetes-associated autoantibodies. -
Association between asymptomatic infections and linear growth in 18-24-month-old Malawian children
Inadequate diet and frequent symptomatic infections are considered major causes of growth stunting in low-income countries, but interventions targeting these risk factors have achieved limited success. Asymptomatic infections can restrict growth, but little is known about their role in global stunting prevalence. We investigated factors related to length-for-age Z-score (LAZ) at 24 months by constructing an interconnected network of various infections, biomarkers of inflammation (as assessed by... -
A Placebo-controlled double-blinded test of the biodiversity hypothesis of immune-mediated diseases: Environmental microbial diversity elicits changes in cytokines and increase in T regulatory cells in young children
CONCLUSIONS: This is the first double-blinded placebo-controlled study to show that daily exposure to microbial biodiversity is associated with immune modulation in humans. The findings support the biodiversity hypothesis of immune-mediated diseases. We conclude that environmental microbiota may contribute to child health, and that adding microbiological diversity to everyday living environment may support immunoregulation. -
Detection of enterovirus RNA in peripheral blood mononuclear cells correlates with the presence of the predisposing allele of the type 1 diabetes risk gene IFIH1 and with disease stage
CONCLUSIONS/INTERPRETATION: Our data indicate that, in peripheral blood, antigen-presenting cells are the predominant source of enterovirus infection, and that infection is correlated with disease stage and genetic predisposition, thereby supporting a role for enterovirus infection prior to disease onset. -
Application of digital PCR for public health-related water quality monitoring
Digital polymerase chain reaction (dPCR) is emerging as a reliable platform for quantifying microorganisms in the field of water microbiology. This paper reviews the fundamental principles of dPCR and its application for health-related water microbiology. The relevant literature indicates increasing adoption of dPCR for measuring fecal indicator bacteria, microbial source tracking marker genes, and pathogens in various aquatic environments. The adoption of dPCR has accelerated recently due to... -
Pancreas Whole Tissue Transcriptomics Highlights the Role of the Exocrine Pancreas in Patients With Recently Diagnosed Type 1 Diabetes
Although type 1 diabetes (T1D) is primarily a disease of the pancreatic beta-cells, understanding of the disease-associated alterations in the whole pancreas could be important for the improved treatment or the prevention of the disease. We have characterized the whole-pancreas gene expression of patients with recently diagnosed T1D from the Diabetes Virus Detection (DiViD) study and non-diabetic controls. Furthermore, another parallel dataset of the whole pancreas and an additional dataset from... -
Indoor green wall affects health-associated commensal skin microbiota and enhances immune regulation: a randomized trial among urban office workers
Urbanization reduces microbiological abundance and diversity, which has been associated with immune mediated diseases. Urban greening may be used as a prophylactic method to restore microbiological diversity in cities and among urbanites. This study evaluated the impact of air-circulating green walls on bacterial abundance and diversity on human skin, and on immune responses determined by blood cytokine measurements. Human subjects working in offices in two Finnish cities (Lahti and Tampere)... -
Sources of dietary gluten in the first 2 years of life and associations with celiac disease autoimmunity and celiac disease in Swedish genetically predisposed children: The Environmental Determinants of Diabetes in the Young (TEDDY) study
CONCLUSIONS: High daily intakes of bread at age 12 mo and of milk cereal drink during the second year of life are associated with increased risk of both CDA and CD in genetically at-risk children. -
Telomere length is not a main factor for the development of islet autoimmunity and type 1 diabetes in the TEDDY study
The Environmental Determinants of Diabetes in the Young (TEDDY) study enrolled 8676 children, 3-4 months of age, born with HLA-susceptibility genotypes for islet autoimmunity (IA) and type 1 diabetes (T1D). Whole-genome sequencing (WGS) was performed in 1119 children in a nested case-control study design. Telomere length was estimated from WGS data using five tools: Computel, Telseq, Telomerecat, qMotif and Motif_counter. The estimated median telomere length was 5.10 kb (IQR 4.52-5.68 kb) using... -
Author Correction: A combined risk score enhances prediction of type 1 diabetes among susceptible children
No abstract -
Heterogeneity of DKA Incidence and Age-Specific Clinical Characteristics in Children Diagnosed With Type 1 Diabetes in the TEDDY Study
CONCLUSIONS: DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.
2021
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Effect of inactivated nature-derived microbial composition on mouse immune system
CONCLUSIONS: These results provide insights on the effect of biodiversity on murine immune system in sterile environment. Subjecting mice to soil-based plant and microbe structures appears to elicit immune response that could be beneficial, for example, in type 2 inflammation-related diseases, that is, allergic diseases. -
Dynamic changes in immune gene co-expression networks predict development of type 1 diabetes
Significant progress has been made in elucidating genetic risk factors influencing Type 1 diabetes (T1D); however, features other than genetic variants that initiate and/or accelerate islet autoimmunity that lead to the development of clinical T1D remain largely unknown. We hypothesized that genetic and environmental risk factors can both contribute to T1D through dynamic alterations of molecular interactions in physiologic networks. To test this hypothesis, we utilized longitudinal blood... -
Long-term biodiversity intervention shapes health-associated commensal microbiota among urban day-care children
CONCLUSIONS: This study shows that a 2-year biodiversity intervention shapes human commensal microbiota, including taxa that have been associated with immune regulation. Results indicate that intervention enriched commensal microbiota and suppressed the potentially pathogenic bacteria on the skin. We recommend future studies that expand intervention strategies to immune response and eventually the incidence of immune-mediated diseases. -
Characterisation of enterovirus RNA detected in the pancreas and other specimens of live patients with newly diagnosed type 1 diabetes in the DiViD study
CONCLUSIONS/INTERPRETATION: EV RNA can be frequently detected in various tissues of patients with type 1 diabetes. At least in some patients, the EV strain in the pancreatic islets may represent a slowly replicating persisting virus. -
Blastocystis in the faeces of children from six distant countries: prevalence, quantity, subtypes and the relation to the gut bacteriome
CONCLUSIONS: Asymptomatic children frequently carry Blastocystis, and co-infection with multiple distinct subtypes is not exceptional. Prevalence and quantity of the organism clearly differ among populations. Blastocystis is linked to both faecal bacteriome diversity and its composition. -
Human Protoparvovirus DNA and IgG in Children and Adults with and without Respiratory or Gastrointestinal Infections
Three human protoparvoviruses, bufavirus (BuV), tusavirus (TuV) and cutavirus (CuV), have recently been discovered in diarrheal stool. BuV has been associated with diarrhea and CuV with cutaneous T-cell lymphoma, but there are hardly any data for TuV or CuV in stool or respiratory samples. Hence, using qPCR and IgG enzyme immunoassays, we analyzed 1072 stool, 316 respiratory and 445 serum or plasma samples from 1098 patients with and without gastroenteritis (GE) or respiratory-tract infections... -
Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life
Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T... -
An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood
CONCLUSIONS: The risk of developing islet autoimmunity declines exponentially with age, and the influence of major genetic factors on this risk is limited to the first few years of life. -
The detection and stability of the SARS-CoV-2 RNA biomarkers in wastewater influent in Helsinki, Finland
Wastewater-based surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is used to monitor the population-level prevalence of the COVID-19 disease. In many cases, due to lockdowns or analytical delays, the analysis of wastewater samples might only be possible after prolonged storage. In this study, the effect of storage conditions on the RNA copy numbers of the SARS-CoV-2 virus in wastewater influent was studied and compared to the persistence of norovirus over time at... -
Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I among Malawian children
CONCLUSIONS: The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways. -
Associations between land cover categories, gaseous PAH levels in ambient air and endocrine signaling predicted from gut bacterial metagenome of the elderly
There is evidence that polycyclic aromatic hydrocarbons (PAHs) and human gut microbiota are associated with the modulation of endocrine signaling pathways. Independently, studies have found associations between air pollution, land cover and commensal microbiota. We are the first to estimate the interaction between land cover categories associated with air pollution or purification, PAH levels and endocrine signaling predicted from gut metagenome among urban and rural populations. The study... -
Faecal regenerating 1B protein concentration is not associated with child growth in rural Malawi
CONCLUSIONS: Faecal REG1B concentration is not associated with LAZ, WAZ, WLZ and MUACZ among 6-30-month-old infants and children in rural Malawi.
2020
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Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life
Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T... -
Detection of Viral -RNA and +RNA Strands in Enterovirus-Infected Cells and Tissues
The current methods to study the distribution and dynamics of viral RNA molecules inside infected cells are not ideal, as electron microscopy and immunohistochemistry can only detect mature virions, and quantitative real-time PCR does not reveal localized distribution of RNAs. We demonstrated here the branched DNA in situ hybridization (bDNA ISH) technology to study both the amount and location of the emerging -RNA and +RNA during acute and persistent enterovirus infections. According to our... -
Associations between land cover categories, gaseous PAH levels in ambient air and endocrine signaling predicted from gut bacterial metagenome of the elderly
There is evidence that polycyclic aromatic hydrocarbons (PAHs) and human gut microbiota are associated with the modulation of endocrine signaling pathways. Independently, studies have found associations between air pollution, land cover and commensal microbiota. We are the first to estimate the interaction between land cover categories associated with air pollution or purification, PAH levels and endocrine signaling predicted from gut metagenome among urban and rural populations. The study... -
Genetic Adaptation of Coxsackievirus B1 during Persistent Infection in Pancreatic Cells
Coxsackie B (CVB) viruses have been associated with type 1 diabetes. We have recently observed that CVB1 was linked to the initiation of the autoimmune process leading to type 1 diabetes in Finnish children. Viral persistency in the pancreas is currently considered as one possible mechanism. In the current study persistent infection was established in pancreatic ductal and beta cell lines (PANC-1 and 1.1B4) using four different CVB1 strains, including the prototype strain and three clinical... -
Faecal regenerating 1B protein concentration is not associated with child growth in rural Malawi
CONCLUSIONS: Faecal REG1B concentration is not associated with LAZ, WAZ, WLZ and MUACZ among 6-30-month-old infants and children in rural Malawi. -
Biodiversity intervention enhances immune regulation and health-associated commensal microbiota among daycare children
As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity... -
A combined risk score enhances prediction of type 1 diabetes among susceptible children
Type 1 diabetes (T1D)-an autoimmune disease that destroys the pancreatic islets, resulting in insulin deficiency-often begins early in life when islet autoantibody appearance signals high risk¹. However, clinical diabetes can follow in weeks or only after decades, and is very difficult to predict. Ketoacidosis at onset remains common^(2,3) and is most severe in the very young^(4,5), in whom it can be life threatening and difficult to treat^(6-9). Autoantibody surveillance programs effectively... -
Differential Detection of Encapsidated versus Unencapsidated Enterovirus RNA in Samples Containing Pancreatic Enzymes-Relevance for Diabetes Studies
Using immunohistochemistry, enterovirus capsid proteins were demonstrated in pancreatic islets of patients with type 1 diabetes. Virus proteins are mainly located in beta cells, supporting the hypothesis that enterovirus infections may contribute to the pathogenesis of type 1 diabetes. In samples of pancreatic tissue, enterovirus RNA was also detected, but in extremely small quantities and in a smaller proportion of cases compared to the enteroviral protein. Difficulties in detecting viral RNA... -
Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study
CONCLUSIONS: The hierarchical order of distinct autoantibody spreading was independent of the first-appearing autoantibody type and was age-dependent and augmented the risk of progression to T1D. -
Eradication of persistent coxsackievirus B infection from a pancreatic cell line with clinically used antiviral drugs
CONCLUSIONS: The identified drugs are feasible candidates for clinical trials among patients with persistent coxsackievirus B infections or chronic enterovirus-associated diseases. -
Enhancing and neutralizing anti-coxsackievirus activities in serum samples from patients prior to development of type 1 diabetes
CONCLUSIONS: Evaluating the anti-enterovirus neutralizing and enhancing activity of serum samples can be useful to investigate further the relationship between enteroviruses and the development of T1D. -
Association of Picornavirus Infections With Acute Otitis Media in a Prospective Birth Cohort Study
CONCLUSIONS: HEVs and HRVs may contribute to the development of AOM in a relatively large proportion of cases. -
Longitudinal Metabolome-Wide Signals Prior to the Appearance of a First Islet Autoantibody in Children Participating in the TEDDY Study
Children at increased genetic risk for type 1 diabetes (T1D) after environmental exposures may develop pancreatic islet autoantibodies (IA) at a very young age. Metabolic profile changes over time may imply responses to exposures and signal development of the first IA. Our present research in The Environmental Determinants of Diabetes in the Young (TEDDY) study aimed to identify metabolome-wide signals preceding the first IA against GAD (GADA-first) or against insulin (IAA-first). We profiled... -
Yard vegetation is associated with gut microbiota composition
Gut microbes play an essential role in the development and functioning of the human immune system. A disturbed gut microbiota composition is often associated with a number of health disorders including immune-mediated diseases. Differences in host characteristics such as ethnicity, living habit and diet have been used to explain differences in the gut microbiota composition in inter-continental comparison studies. As our previous studies imply that daily skin contact with organic gardening... -
Distinct Growth Phases in Early Life Associated With the Risk of Type 1 Diabetes: The TEDDY Study
CONCLUSIONS: Growth patterns in early life better clarify how specific growth phases are associated with the development of T1D.
2019
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Metagenomics of the faecal virome indicate a cumulative effect of enterovirus and gluten amount on the risk of coeliac disease autoimmunity in genetically at risk children: the TEDDY study
CONCLUSIONS: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA. -
Metabolite-related dietary patterns and the development of islet autoimmunity
The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases... -
Coxsackievirus B Persistence Modifies the Proteome and the Secretome of Pancreatic Ductal Cells
The group B Coxsackieviruses (CVB), belonging to the Enterovirus genus, can establish persistent infections in human cells. These persistent infections have been linked to chronic diseases including type 1 diabetes. Still, the outcomes of persistent CVB infections in human pancreas are largely unknown. We established persistent CVB infections in a human pancreatic ductal-like cell line PANC-1 using two distinct CVB1 strains and profiled infection-induced changes in cellular protein expression... -
Temporal variation in indoor transfer of dirt-associated environmental bacteria in agricultural and urban areas
An agricultural environment and exposure to diverse environmental microbiota has been suggested to confer protection against immune-mediated disorders. As an agricultural environment may have a protective role, it is crucial to determine whether the limiting factors in the transfer of environmental microbiota indoors are the same in the agricultural and urban environments. We explored how sampling month, garden diversity and animal ownership affected the indoor-transfer of environmental... -
Endocrine disruption and commensal bacteria alteration associated with gaseous and soil PAH contamination among daycare children
Polycyclic aromatic hydrocarbons (PAHs) are priority environmental pollutants that cause adverse health effects. PAHs belong to endocrine signaling disruptors to which children are sensitive to. Recent evidence suggests that PAH pollution alters the abundance of environmental bacteria that is associated with health outcomes. The alteration of environmental and commensal microbiota by PAH pollution has never been connected to endocrine signaling pathways. To estimate the risk of endocrine... -
Early childhood infections and the use of antibiotics and antipyretic-analgesics in Finland, Estonia and Russian Karelia
CONCLUSION: Infections and the use of antibiotics and antipyretic-analgesics in early childhood were most frequent in Finland, where socio-economic conditions are the most developed and microbial encounters are sparse. This may reflect on the hygiene hypothesis, a less effective immune system that allows normally harmless microbes to attack and cause clinical infections. -
Presence of Giardia lamblia in stools of six- to 18-month old asymptomatic Malawians is associated with children's growth failure
CONCLUSION: Asymptomatic G. lamblia infection was mainly associated with growth reduction in certain three-month periods. The result refers to the chronic nature of G. lamblia infection. -
Predicting Islet Cell Autoimmunity and Type 1 Diabetes: An 8-Year TEDDY Study Progress Report
CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially. -
Rhinoviruses in infancy and risk of immunoglobulin E sensitization
Previous data about the role of viruses in the development of allergic immunoglobulin E (IgE) sensitization are contradictory. The aim of this study was to determine the possible associations between exposure to different viruses (rhinovirus, enterovirus, norovirus, and parechovirus) during the first year of life and IgE sensitization. Viruses were analyzed from stool samples collected monthly from infants participating in a prospective birth cohort study. From that study, 244 IgE sensitized...