Browsing by Author "Ilonen, Jorma"

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  • Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life
    (2019-03-01) Vatanen, Tommi; Plichta, Damian R.; Somani, Juhi; Münch, Philipp C.; Arthur, Timothy D.; Hall, Andrew Brantley; Rudolf, Sabine; Oakeley, Edward J.; Ke, Xiaobo; Young, Rachel A.; Haiser, Henry J.; Kolde, Raivo; Yassour, Moran; Luopajärvi, Kristiina; Siljander, Heli; Virtanen, Suvi M.; Ilonen, Jorma; Uibo, Raivo; Tillmann, Vallo; Mokurov, Sergei; Dorshakova, Natalya; Porter, Jeffrey A.; McHardy, Alice C.; Lähdesmäki, Harri; Vlamakis, Hera; Huttenhower, Curtis; Knip, Mikael; Xavier, Ramnik J.
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.
  • GIMAP GTPase Family Genes: Potential Modifiers in Autoimmune Diabetes, Asthma, and Allergy
    (2015) Heinonen, Mirkka T.; Laine, Antti-Pekka; Soderhall, Cilla; Gruzieva, Olena; Rautio, Sini; Melen, Erik; Pershagen, Goran; Lahdesmaki, Harri J.; Knip, Mikael; Ilonen, Jorma; Henttinen, Tiina A.; Kere, Juha; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
  • Metabolic regulation in progression to autoimmune diabetes
    (2011) Sysi-Aho, Marko; Ermolov, Andrey; Gopalacharyulu, Peddinti V.; Tripathi, Abhishek; Seppänen-Laakso, Tuulikki; Maukonen, Johanna; Mattila, Ismo; Ruohonen, Suvi T.; Vähätalo, Laura; Yetukuri, Laxman; Härkönen, Taina; Lindfors, Erno; Nikkilä, Janne; Ilonen, Jorma; Simell, Olli; Saarela, Maria; Knip, Mikael; Kaski, Samuel; Savontaus, Eriika; Oresic, Matej
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Recent evidence from serum metabolomics indicates that specific metabolic disturbances precede β-cell autoimmunity in humans and can be used to identify those children who subsequently progress to type 1 diabetes. The mechanisms behind these disturbances are unknown. Here we show the specificity of the pre-autoimmune metabolic changes, as indicated by their conservation in a murine model of type 1 diabetes. We performed a study in non-obese prediabetic (NOD) mice which recapitulated the design of the human study and derived the metabolic states from longitudinal lipidomics data. We show that female NOD mice who later progress to autoimmune diabetes exhibit the same lipidomic pattern as prediabetic children. These metabolic changes are accompanied by enhanced glucose-stimulated insulin secretion, normoglycemia, upregulation of insulinotropic amino acids in islets, elevated plasma leptin and adiponectin, and diminished gut microbial diversity of the Clostridium leptum group. Together, the findings indicate that autoimmune diabetes is preceded by a state of increased metabolic demands on the islets resulting in elevated insulin secretion and suggest alternative metabolic related pathways as therapeutic targets to prevent diabetes.
  • Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes
    (2023-12) Hirvonen, M. Karoliina; Lietzén, Niina; Moulder, Robert; Bhosale, Santosh D.; Koskenniemi, Jaakko; Vähä-Mäkilä, Mari; Nurmio, Mirja; Orešič, Matej; Ilonen, Jorma; Toppari, Jorma; Veijola, Riitta; Hyöty, Heikki; Lähdesmäki, Harri; Knip, Mikael; Cheng, Lu; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n = 10) and compared these with similar measurements from matched children who were either positive for a single autoantibody (n = 10) or autoantibody negative (n = 10). Following statistical analysis of the longitudinal data, targeted serum proteomics was used to verify 11 proteins putatively associated with the disease development in a similar yet independent and larger cohort of children who progressed to the disease within 5 years of age (n = 31) and matched autoantibody negative children (n = 31). These data reiterated extensive age-related trends for protein levels in young children. Further, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes, in comparison to autoantibody negative children.
  • Standard of hygiene and immune adaptation in newborn infants
    (2014) Kallionpää, Henna; Laajala, Essi; Öling, Viveka; Härkönen, Taina; Tillmann, Vallo; Dorshakova, Natalya V.; Ilonen, Jorma; Lähdesmäki, Harri; Knip, Mikael; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    The prevalence of immune-mediated diseases, such as allergies and type 1 diabetes, is on the rise in the developed world. In order to explore differences in the gene expression patterns induced in utero in infants born in contrasting standards of living and hygiene, we collected umbilical cord blood RNA samples from infants born in Finland (modern society), Estonia (rapidly developing society) and the Republic of Karelia, Russia (poor economic conditions). The whole blood transcriptome of Finnish and Estonian neonates differed from their Karelian counterparts, suggesting exposure to toll-like receptor (TLR) ligands and a more matured immune response in infants born in Karelia. These results further support the concept of a conspicuous plasticity in the developing immune system: the environmental factors that play a role in the susceptibility/protection towards immune-mediated diseases begin to shape the neonatal immunity already in utero and direct the maturation in accordance with the surrounding microbial milieu.
  • Umbilical cord blood DNA methylation in children who later develop type 1 diabetes
    (2022-09) Laajala, Essi; Kalim, Ubaid Ullah; Grönroos, Toni; Rasool, Omid; Halla-aho, Viivi; Konki, Mikko; Kattelus, Roosa; Mykkänen, Juha; Nurmio, Mirja; Vähä-Mäkilä, Mari; Kallionpää, Henna; Lietzén, Niina; Ghimire, Bishwa R.; Laiho, Asta; Hyöty, Heikki; Elo, Laura L.; Ilonen, Jorma; Knip, Mikael; Lund, Riikka J.; Orešič, Matej; Veijola, Riitta; Lähdesmäki, Harri; Toppari, Jorma; Lahesmaa, Riitta
     A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
    Aims/hypothesis: Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes. Methods: Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis. Results: No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate <0.05. Conclusions/interpretation: Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset. Graphical abstract: [Figure not available: see fulltext.]