Browsing by Subject "EARLY-LIFE"

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  • Premenopausal Breast Canc Collabor (2018)
    IMPORTANCE The association between increasing body mass index (BMI; calculated as wei ght in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. OBJECTIVE To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. DESIGN, SETTING, AND PARTICIPANTS This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1,1963, through December 31, 2013, and data were analyzed from September 1.2013, through December 31, 2017. EXPOSURES Body mass index at ages 18 to 24, 25 to 34,35 to 44, and 45 to 54 years. MAIN OUTCOMES AND MEASURES Invasive or in situ premenopausal breast cancer. RESULTS Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m(2) [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI >= 35.0 vs CONCLUSIONS AND RELEVANCE The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.
  • Girchenko, Polina; Lahti, Jari; Czamara, Darina; Knight, Anna K.; Jones, Meaghan J.; Suarez Figueiredo, Anna; Hämäläinen, Esa; Kajantie, Eero; Laivuori, Hannele; Villa, Pia M.; Reynolds, Rebecca M.; Kobor, Michael S.; Smith, Alicia K.; Binder, Elisabeth B.; Räikkönen, Katri (2017)
    Background: A recent study has shown that it is possible to accurately estimate gestational age (GA) at birth from the DNA methylation (DNAm) of fetal umbilical cord blood/newborn blood spots. This DNAm GA predictor may provide additional information relevant to developmental stage. In 814 mother-neonate pairs, we evaluated the associations between DNAm GA and a number of maternal and offspring characteristics. These characteristics reflect prenatal environmental adversity and are expected to influence newborn developmental stage. Results: DNAm GA acceleration (GAA; i.e., older DNAm GA than chronological GA) of the offspring at birth was associated with maternal age of over 40 years at delivery, pre-eclampsia and fetal demise in a previous pregnancy, maternal pre-eclampsia and treatment with antenatal betamethasone in the index pregnancy, lower neonatal birth size, lower 1-min Apgar score, and female sex. DNAm GA deceleration (GAD; i.e., younger DNAm GA than chronological GA) of the offspring at birth was associated with insulin-treated gestational diabetes mellitus (GDM) in a previous pregnancy and Sjogren's syndrome. These findings were more accentuated when the DNAm GA calculation was based on the raw difference between DNAm GA and GA than on the residual from the linear regression of DNAm GA on GA. Conclusions: Our findings show that variations in the DNAm GA of the offspring at birth are associated with a number of maternal and offspring characteristics known to reflect exposure to prenatal environmental adversity. Future studies should be aimed at determining if this biological variation is predictive of developmental adversity.
  • Eshriqui, Ilana; Viljakainen, Heli T.; Ferreira, Sandra; Raju, Sajan C.; Weiderpass, Elisabete; Figueiredo, Rejane A. O. (2020)
    Background Breastfeeding contributes to gastrointestinal microbiota colonization in early life, but its long-term impact is inconclusive. We aimed to evaluate whether the type of feeding during the first six months of life was associated with oral microbiota in adolescence. Methods This is a cross-sectional sub-study using baseline information of 423 adolescents from the Finnish Health in Teens (Fin-HIT) cohort. Type of feeding was recalled by parents and dichotomized as (i) No infant formula; (ii) Infant formula (breastmilk + formula or only formula). Saliva microbiota was analysed using 16S rRNA (V3-V4) sequencing. Alpha diversity and beta diversity were compared between feeding type groups using ANCOVA and PERMANOVA, respectively. Differential bacteria abundance was tested using appropriate general linear models. Results Mean age and body mass index were 11.7 years and 18.0 kg/m(2), respectively. The No formula group contained 41% of the participants. Firmicutes (51.0%), Bacteroidetes (19.1%), and Proteobacteria (16.3%) were the most abundant phyla among all participants. Alpha and beta diversity indices did not differ between the two feeding groups. Three Operational Taxonomic Units (OTUs) belonging to Eubacteria and Veillonella genera (phylum Firmicutes) were more abundant in the No formula than in the Infant formula group (log2fold changes/ p - values - 0.920/ <0.001, - 0.328/ 0.001, - 0.577/ 0.004). Conclusion Differences exist in abundances of some OTUs in adolescence according to feeding type during the first six months of life, but our findings do not support diversity and overall oral microbiota composition in adolescents being affected by early feeding type.
  • Ruokolainen, Lasse; Parkkola, Anna; Karkman, Antti; Sinkko, Hanna; Peet, Aleksandr; Hämäläinen, Anu-Maaria; von Hertzen, Leena; Tillmann, Vallo; Koski, Katriina; Virtanen, Suvi M.; Niemelä, Onni; Haahtela, Tari; Knip, Mikael (2020)
    Background Allergic diseases are more common in Finland than in Estonia, which-according to the biodiversity hypothesis-could relate to differences in early microbial exposures. Methods We aimed at defining possible microbial perturbations preceding early atopic sensitization. Stool, nasal and skin samples of 6-month-old DIABIMMUNE study participants with HLA susceptibility to type 1 diabetes were collected. We compared microbiotas of sensitized (determined by specific IgE results at 18 months of age) and unsensitized Estonian and Finnish children. Results Sensitization was differentially targeted between populations, as egg-specific and birch pollen-specific IgE was more common in Finland. Microbial diversity and community composition also differed; the genusAcinetobacterwas more abundant in Estonian skin and nasal samples. Particularly, the strain-level profile ofAcinetobacter lwoffiiwas more diverse in Estonian samples. Early microbiota was not generally associated with later sensitization. Microbial composition tended to differ between children with or without IgE-related sensitization, but only in Finland. While land-use pattern (ie green areas vs. urban landscapes around the children's homes) was not associated with microbiota as a whole, it associated with the composition of the genusAcinetobacter. Breastfeeding affected gut microbial composition and seemed to protect from sensitization. Conclusions In accordance with the biodiversity hypothesis, our results support disparate early exposure to environmental microbes between Finnish and Estonian children and suggest a significant role of the genusAcinetobacterin the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open.
  • Hyytiainen, Heidi K.; Jayaprakash, Balamuralikrishna; Kirjavainen, Pirkka V.; Saari, Sampo E.; Holopainen, Rauno; Keskinen, Jorma; Hämeri, Kaarle; Hyvarinen, Anne; Boor, Brandon E.; Taubel, Martin (2018)
    Background: Floor dust is commonly used for microbial determinations in epidemiological studies to estimate early-life indoor microbial exposures. Resuspension of floor dust and its impact on infant microbial exposure is, however, little explored. The aim of our study was to investigate how floor dust resuspension induced by an infant's crawling motion and an adult walking affects infant inhalation exposure to microbes. Results: We conducted controlled chamber experiments with a simplified mechanical crawling infant robot and an adult volunteer walking over carpeted flooring. We applied bacterial 16S rRNA gene sequencing and quantitative PCR to monitor the infant breathing zone microbial content and compared that to the adult breathing zone and the carpet dust as the source. During crawling, fungal and bacterial levels were, on average, 8- to 21-fold higher in the infant breathing zone compared to measurements from the adult breathing zone. During walking experiments, the increase in microbial levels in the infant breathing zone was far less pronounced. The correlation in rank orders of microbial levels in the carpet dust and the corresponding infant breathing zone sample varied between different microbial groups but was mostly moderate. The relative abundance of bacterial taxa was characteristically distinct in carpet dust and infant and adult breathing zones during the infant crawling experiments. Bacterial diversity in carpet dust and the infant breathing zone did not correlate significantly. Conclusions: The microbiota in the infant breathing zone differ in absolute quantitative and compositional terms from that of the adult breathing zone and of floor dust. Crawling induces resuspension of floor dust from carpeted flooring, creating a concentrated and localized cloud of microbial content around the infant. Thus, the microbial exposure of infants following dust resuspension is difficult to predict based on common house dust or bulk air measurements. Improved approaches for the assessment of infant microbial exposure, such as sampling at the infant breathing zone level, are needed.
  • Garn, Holger; Bahn, Sabine; Baune, Bernhard T.; Binder, Elisabeth B.; Bisgaard, Hans; Chatila, Talal A.; Chavakis, Triantafyllos; Culmsee, Carsten; Dannlowski, Udo; Gay, Steffen; Gern, James; Haahtela, Tari; Kircher, Tilo; Mueller-Ladner, Ulf; Neurath, Markus F.; Preissner, Klaus T.; Reinhardt, Christoph; Rook, Graham; Russell, Shannon; Schmeck, Bernd; Stappenbeck, Thaddeus; Steinhoff, Ulrich; van Os, Jim; Weiss, Scott; Zemlin, Michael; Renz, Harald (2016)
    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Rontgen Symposium (October 16-18, 2014, in Marburg, Germany) to discuss recent developments in this field. These include a concept of biodiversity; the contribution of urbanization, lifestyle factors, and nutrition (eg, vitamin D); and new mechanisms of metabolic and immune dysregulation, such as extracellular and intracellular RNAs and cellular and mitochondrial stress. Epigenetic mechanisms contribute further to altered gene expression and therefore to the development of chronic inflammation. These novel findings provide the foundation for further development of preventive and therapeutic strategies.
  • Li, Shuxia; Wang, Weijing; Zhang, Dongfeng; Li, Weilong; Lund, Jesper; Kruse, Torben; Mengel-From, Jonas; Christensen, Kaare; Tan, Qihua (2021)
    Background: Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity. Methods: Using a high-throughput array platform for DNA methylome profiling, we conducted a case-control epigenome-wide association study on early-life exposure to Chinese famine in 79 adults born during 1959-1961 and compared to 105 unexposed subjects born 1963-1964. Results: The single CpG site analysis of whole epigenome revealed a predominant pattern of decreased DNA methylation levels associated with fetal exposure to famine. Four CpG sites were detected with p < 1e-06 (linked to EHMT1, CNR1, UBXN7 and ESM1 genes), 16 CpGs detected with 1e-06 < p < 1e-05 and 157 CpGs with 1e-05 < p < 1e-04, with a predominant pattern of hypomethylation. Functional annotation to genes and their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders and metabolism. Multiple sites analysis detected two top-rank differentially methylated regions harboring RNF39 on chromosome 6 and PTPRN2 on chromosome 7, both showing epigenetic association with stress-related conditions. Conclusion: Early-life exposure to famine could mediate DNA methylation regulations that persist into adulthood with broad impacts in the activities of genes and biological pathways. Results from this study provide new clues to the epigenetic embedding of early-life adversity and its impacts on adult health.
  • the DIABIMMUNE Study Group; Mustonen, Neea; Siljander, Heli; Peet, Aleksandr; Tillmann, Vallo; Härkönen, Taina; Ilonen, Jorma; Hyöty, Heikki; Knip, Mikael (2019)
    Aim Infections in early childhood are common reasons to seek medical attention. This study compares the prevalence of infections, and the use of antibiotics and antipyretic-analgesics, in children from Finland, Estonia and Russian Karelia. Methods Children with a genetically increased risk for type 1 diabetes (N = 797) were observed from birth up to 3 years of age. Illnesses and medications were reported by parents continuously. All reported infections, antibiotics and antipyretic-analgesics were compared between Finland and Estonia, and to a lesser extent with Russian Karelia, due to poor study compliance. Results Compared with Estonians, Finns reported more infections during the first and second years of life. During the follow-up, Finnish children had 10 infections while Estonians only had 8 (p <0.001). Finns also used more antibiotics and antipyretic-analgesics in each year during the follow-up. Russian Karelians reported the lowest frequency of infections and the most infrequent use of antibiotics and antipyretic-analgesics in the first two years of life. 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.
  • Frei, Remo; Ferstl, Ruth; Roduit, Caroline; Ziegler, Mario; Schiavi, Elisa; Barcik, Weronika; Rodriguez-Perez, Noelia; Wirz, Oliver F.; Wawrzyniak, Marcin; Pugin, Benoit; Nehrbass, Dirk; Jutel, Marek; Smolinska, Sylwia; Konieczna, Patrycja; Bieli, Christian; Loeliger, Susanne; Waser, Marco; Pershagen, Goeran; Riedler, Josef; Depner, Martin; Schaub, Bianca; Genuneit, Jon; Renz, Harald; Pekkanen, Juha; Karvonen, Anne M.; Dalphin, Jean-Charles; van Hage, Marianne; Doekes, Gert; Akdis, Mubeccel; Braun-Fahrlander, Charlotte; Akdis, Cezmi A.; von Mutius, Erika; O'Mahony, Liam; Lauener, Roger P.; Prevention Allergy Risk Factors Se; Protection Against Allergy Study R (2018)
    Background: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. Objective: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. Methods: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. Results: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17(+) T-cell numbers and supported differentiation of regulatory T cells. Conclusions: In addition to microbial exposure, increased exposure to non microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.
  • Kirjavainen, Pirkka V.; Karvonen, Anne M.; Adams, Rachel I.; Täubel, Martin; Roponen, Marjut; Tuoresmäki, Pauli; Loss, Georg; Jayaprakash, Balamuralikrishna; Depner, Martin; Ege, Markus Johannes; Renz, Harald; Pfefferle, Petra Ina; Schaub, Bianca; Lauener, Roger; Hyvärinen, Anne; Knight, Rob; Heederik, Dick J. J.; von Mutius, Erika; Pekkanen, Juha (2019)
    Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today(1). The asthma-protective effect of farms appears to be associated with rich home dust microbiota(2,3), which could be used to model a health-promoting indoor microbiome. Here we show by modeling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts(4) that in children who grow up in non-farm homes, asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children(2) and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears to be a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention.
  • Huuki, Hanna; Ahvenjaervi, Seppo; Lidauer, Paula; Popova, Milka; Vilkki, Johanna; Vanhatalo, Aila; Tapio, Ilma (2022)
    The development of the functional rumen in calves involves a complex interplay between the host and host-related microbiome. Attempts to modulate rumen microbial community establishment may therefore have an impact on weaning success, calf health, and animal performance later in life. In this experiment, we aimed to elucidate how rumen liquid inoculum from an adult cow, provided to calves during the pre-weaning period, influences the establishment of rumen bacterial, archaeal, fungal, and ciliate protozoan communities in monozygotic twin calves (n = 6 pairs). The calves were divided into treatment (T-group) and control (C-group) groups, where the T-group received fresh rumen liquid as an oral inoculum during a 2-8-week period. The C-group was not inoculated. The rumen microbial community composition was determined using bacterial and archaeal 16S ribosomal RNA (rRNA) gene, protozoal 18S rRNA gene, and fungal ITS1 region amplicon sequencing. Animal weight gain and feed intake were monitored throughout the experiment. The T-group tended to have a higher concentrate intake (Treatment: p < 0.08) and had a significantly higher weekly weight gain (Treatment: p < 0.05), but no significant difference in volatile fatty acid concentrations between the groups was observed. In the T-group, the inoculum stimulated the earlier establishment of mature rumen-related bacterial taxa, affecting significant differences between the groups until 6 weeks of age. The inoculum also increased the archaeal operational taxonomic unit (OTU) diversity (Treatment: p < 0.05) but did not affect the archaeal quantity. Archaeal communities differed significantly between groups until week 4 (p = 0.02). Due to the inoculum, ciliate protozoa were detected in the T-group in week 2, while the C-group remained defaunated until 6 weeks of age. In week 8, Eremoplastron dilobum was the dominant ciliate protozoa in the C-group and Isotricha sp. in the T-group, respectively. The Shannon diversity of rumen anaerobic fungi reduced with age (Week: p < 0.01), and community establishment was influenced by a change of diet and potential interaction with other rumen microorganisms. Our results indicate that an adult cow rumen liquid inoculum enhanced the maturation of bacterial and archaeal communities in pre-weaning calves' rumen, whereas its effect on eukaryotic communities was less clear and requires further investigation.
  • Ruokolainen, L.; von Hertzen, L.; Fyhrquist, N.; Laatikainen, T.; Lehtomaki, J.; Auvinen, P.; Karvonen, A. M.; Hyvarinen, A.; Tillmann, V.; Niemela, O.; Knip, M.; Haahtela, T.; Pekkanen, J.; Hanski, I. (2015)
  • BIOS Consortium; Early Growth Genetics EGG Conso; Alves, Alexessander Couto; De Silva, N. Maneka G.; Cousminer, Diana L.; Eriksson, Johan G.; Widen, Elisabeth (2019)
    Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
  • Ruokolainen, Lasse; Lehtimaki, Jenni; Karkman, Antti; Haahtela, Tari; von Hertzen, Leena; Fyhrquist, Nanna (2017)
    The western world has witnessed a rising epidemic of chronic inflammatory disorders, such as allergies and asthma. This epidemic is expected to spread also to the rest of the world, where allergies have to date been practically absent, along with adoption of western lifestyle. In parallel, biological diversity is globally declining. This inspired Ilkka Hanski, together with medical doctors, to formulate the biodiversity hypothesis of allergic disease. This hypothesis proposes that reduced contact with natural environments, including natural microbial diversity, is associated with unhealthy human microbiota, less able to educate the immune system. Contact with beneficial bacteria, particularly early in life, seems to be instrumental to the normal development of immune responses. Changes in lifestyle and diet, destruction of natural environments, and urbanisation threaten our natural exposure to these beneficial bacteria and thus also reduce their impact on our physiology. To ensure a healthy life, we need to preserve biodiversity in the environment and make sure it finds a favourable home in us. In this review, we will focus on the role of commensal microbiota in human health and wellbeing, as well as the interaction between our microbiota and environmental microbiota, highlighting the contribution of Ilkka Hanski.
  • Shan, Yifan; Wu, Weidong; Fan, Wei; Haahtela, Tari; Zhang, Guicheng (2019)
    People spend a lot of time indoors and the indoor microbiome is a major part of the environment that we are exposed to. However, awareness of the exposure to the indoor microbiome and its health effects remains poor. Outdoor environment (soil and air), indoor sources (ventilation, dampness and building materials), human occupants, and pets compose the indoor microbial community. It has been estimated that up to 500-1000 different species can be present in house dust. House dust is a major source and reservoir of indoor microbiome, which influences human microbiome and determines health and disease. Herein, we review the origins and the components of the fungal and bacterial communities in house dust and their possible effect on human health, in particular on allergic disorders, intestinal microbiome, and immune responses. We expect to lay a solid foundation for the further study on the mechanisms of how the house dust microbes interact with the host microbiome and the human immune system.
  • Haahtela, Tari; Alenius, Harri; Lehtimäki, Jenni; Sinkkonen, Aki; Fyhrquist, Nanna; Hyöty, Heikki; Ruokolainen, Lasse; Mäkelä, Mika J. (2021)
    Increase of allergic conditions has occurred at the same pace with the Great Acceleration, which stands for the rapid growth rate of human activities upon earth from 1950s. Changes of environment and lifestyle along with escalating urbanization are acknowledged as the main underlying causes. Secondary (tertiary) prevention for better disease control has advanced considerably with innovations for oral immunotherapy and effective treatment of inflammation with corticosteroids, calcineurin inhibitors, and biological medications. Patients are less disabled than before. However, primary prevention has remained a dilemma. Factors predicting allergy and asthma risk have proven complex: Risk factors increase the risk, while protective factors counteract them. Interaction of human body with environmental biodiversity with micro-organisms and biogenic compounds as well as the central role of epigenetic adaptation in immune homeostasis have given new insight. Allergic diseases are good indicators of the twisted relation to environment. In various non-communicable diseases, the protective mode of the immune system indicates low-grade inflammation without apparent cause. Giving microbes, pro- and prebiotics, has shown some promise in prevention and treatment. The real-world public health programme in Finland (2008-2018) emphasized nature relatedness and protective factors for immunological resilience, instead of avoidance. The nationwide action mitigated the allergy burden, but in the lack of controls, primary preventive effect remains to be proven. The first results of controlled biodiversity interventions are promising. In the fast urbanizing world, new approaches are called for allergy prevention, which also has a major cost saving potential.
  • Karvonen, Anne M.; Kirjavainen, Pirkka V.; Täubel, Martin; Jayaprakash, Balamuralikrishna; Adams, Rachel I.; Sordillo, Joanne E.; Gold, Diane R.; Hyvärinen, Anne; Remes, Sami; von Mutius, Erika; Pekkanen, Juha (2019)
    Background: Early-life indoor bacterial exposure is associated with the risk of asthma, but the roles of specific bacterial genera are poorly understood. Objective: We sought to determine whether individual bacterial genera in indoor microbiota predict the development of asthma. Methods: Dust samples from living rooms were collected at 2 months of age. The dust microbiota was characterized by using Illumina MiSeq sequencing amplicons of the bacterial 16S ribosomal RNA gene. Children (n = 373) were followed up for ever asthma until the age of 10.5 years. Results: Richness was inversely associated with asthma after adjustments (P = .03). The phylogenetic microbiota composition in asthmatics patients' homes was characteristically different from that in nonasthmatic subjects' homes (P = .02, weighted UniFrac, adjusted association, permutational multivariate analysis of variance, PERMANOVA-S). The first 2 axis scores of principal coordinate analysis of the weighted UniFrac distance matrix were inversely associated with asthma. Of 658 genera detected in the dust samples, the relative abundances of 41 genera correlated (r > vertical bar 0.4 vertical bar) with one of these axes. Lactococcus genus was a risk factor for asthma (adjusted odds ratio, 1.36 [95% CI, 1.13-1.63] per interquartile range change). The abundance of 12 bacterial genera (mostly from the Actinomycetales order) was associated with lower asthma risk (P <.10), although not independently of each other. The sum relative abundance of these 12 intercorrelated genera was significantly protective and explained the majority of the association of richness with less asthma. Conclusion: Our data confirm that phylogenetic differences in the microbiota of infants' homes are associated with subsequent asthma risk and suggest that communities of selected bacteria are more strongly linked to asthma protection than individual bacterial taxa or mere richness.
  • Heinonen, Santtu; Rodriguez-Fernandez, Rosa; Diaz, Alejandro; Oliva Rodriguez-Pastor, Silvia; Ramilo, Octavio; Mejias, Asuncion (2019)
    Of all respiratory viruses that affect infants, respiratory syncytial virus (RSV) and rhinovirus (RV) represent the leading pathogens causing acute disease (bronchiolitis) and are associated with the development of recurrent wheezing and asthma. The immune system in infants is still developing, and several factors contribute to their increased susceptibility to viral infections. These factors include differences in pathogen detection, weaker interferon responses, lack of immunologic memory toward the invading pathogen, and T-cell responses that are balanced to promote tolerance and restrain inflammation. These aspects are reviewed here with a focus on RSV and RV infections.
  • Pirilä, Satu Maaria; Taskinen, Mervi; Viljakainen, Heli; Kajosaari, Merja; Turanlahti, Maila; Saarinen-Pihkala, Ulla M.; Mäkitie, Outi (2011)
  • Martikainen, Maria-Viola; Rönkkö, Teemu J.; Schaub, Bianca; Täubel, Martin; Gu, Cheng; Wong, Gary W. K.; Li, Jing; Pekkanen, Juha; Komppula, Mika; Hirvonen, Maija-Riitta; Jalava, Pasi I.; Roponen, Marjut (2018)
    Background Studies conducted in farm environments suggest that diverse microbial exposure promotes children's lung health. The underlying mechanisms are unclear, and the development of asthma-preventive strategies has been delayed. More comprehensive investigation of the environment-induced immunoregulation is required for better understanding of asthma pathogenesis and prevention. Exposure to air pollution, including particulate matter (PM), is a risk factor for asthma, thus providing an excellent counterpoint for the farm-effect research. Lack of comparable data, however, complicates interpretation of the existing information. We aimed to explore the immunoregulatory effects of cattle farm dust (protective, Finland) and urban air PM (high-risk, China) for the first time using identical research methods. Methods We stimulated PBMCs of 4-year-old children (N = 18) with farm dust and size-segregated PM and assessed the expression of immune receptors CD80 and ILT4 on dendritic cells and monocytes as well as cytokine production of PBMCs. Environmental samples were analysed for their composition. Results Farm dust increased the percentage of cells expressing CD80 and the cytokine production of children's immune cells, whereas PM inhibited the expression of important receptors and the production of soluble mediators. Although PM samples induced parallel immune reactions, the size-fraction determined the strength of the effects. Conclusions Our study demonstrates the significance of using the same research framework when disentangling shared and distinctive immune pathways operating in different environments. Observed stimulatory effects of farm dust and inhibitory effects of PM could shape responses towards respiratory pathogens and allergens, and partly explain differences in asthma prevalence between studied environments.