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Background: After the Second World War, the population living in the Karelian region was strictly divided by the "iron curtain" between Finland and Russia. This resulted in different lifestyle, standard of living, and exposure to the environment. Allergic manifestations and sensitization to common allergens have been much more common on the Finnish compared to the Russian side. Objective: The remarkable allergy disparity in the Finnish and Russian Karelia calls for immunological explanations. Methods: Young people, aged 15‐20 years, in the Finnish (n = 69) and Russian (n = 75) Karelia were studied. The impact of genetic variation on the phenotype was studied by a genome‐wide association analysis. Differences in gene expression (transcriptome) were explored from the blood mononuclear cells (PBMC) and related to skin and nasal epithelium microbiota and sensitization. Results: The genotype differences between the Finnish and Russian populations did not explain the allergy gap. The network of gene expression and skin and nasal microbiota was richer and more diverse in the Russian subjects. When the function of 261 differentially expressed genes was explored, innate immunity pathways were suppressed among Russians compared to Finns. Differences in the gene expression paralleled the microbiota disparity. High Acinetobacter abundance in Russians correlated with suppression of innate immune response. High‐total IgE was associated with enhanced anti‐viral response in the Finnish but not in the Russian subjects. Conclusions and clinical relevance: Young populations living in the Finnish and Russian Karelia show marked differences in genome‐wide gene expression and host contrasting skin and nasal epithelium microbiota. The rich gene‐microbe network in Russians seems to result in a better‐balanced innate immunity and associates with low allergy prevalence. [ABSTRACT FROM AUTHOR]

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 genus Acinetobacter was more abundant in Estonian skin and nasal samples. Particularly, the strain‐level profile of Acinetobacter lwoffii was 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 genus Acinetobacter. 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 genus Acinetobacter in the allergy gap between the two populations. The significance of the observed differences for later allergic sensitization remains open. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Atopic allergy is much more common in Finnish compared with Russian Karelia, although these areas are geographically and genetically close. To explore the role of environmental chemicals on the atopy difference a random sample of 200 individuals, 25 atopic and 25 non-atopic school-aged children and their mothers, were studied. Atopy was defined as having at least one positive skin prick test response to 14 common inhalant and food allergens tested. Concentrations of 11 common environmental pollutants were measured in blood samples. Results: Overall, the chemical levels were much higher in Russia than in Finland, except for 2,2',4,4'-tetra-bromodiphenyl ether (BDE47). In Finland but not in Russia, the atopic children had higher concentrations of polychlorinated biphenyls and 1,1-Dichloro-2,2-bis-(p-chlorophenyl)-ethylene (DDE) than the non-atopic children. In Russia but not in Finland, the atopic mothers had higher DDE concentrations than the non-atopic mothers. Conclusions: Higher concentrations of common environmental chemicals were measured in Russian compared with Finnish Karelian children and mothers. The chemicals did not explain the higher prevalence of atopy on the Finnish side. [ABSTRACT FROM AUTHOR]

Urban living in built environments, combined with the use of processed water and food, may not provide the microbial stimulation necessary for a balanced development of immune function. Many chronic inflammatory disorders, including allergic, autoimmune, metabolic, and even some behavioural disorders, are linked to alteration in the human commensal microbiota. Sedentary lifestyle is associated with reduced exposure to a broad spectrum of environmental micro-organisms and surplus energy balance, both risk factors of chronic inflammatory disorders. According to the Biodiversity Hypothesis, an environment with diverse macrobiota and microbiota modifies and enriches the human microbiota, which in turn is crucial in the development and maintenance of appropriate immune function. These issues were discussed in the symposium 'Chronic Inflammation, Lifestyle and Environment', held in Helsinki, 20-22 August 2014, under the sponsorship of the Yrjö Jahnsson Foundation. This paper briefly outlines the recent findings in the context of the environment, lifestyle, and health; discusses the forces that undermine immune tolerance in urban environments; and highlights the possibilities to restore broken immune tolerance among urban dwellers, summarizing the main messages in four statements and calling for actions to combat major public health threats. [ABSTRACT FROM AUTHOR]

Rapidly declining biodiversity may be a contributing factor to another global megatrend—the rapidly increasing prevalence of allergies and other chronic inflammatory diseases among urban populations worldwide. According to the "biodiversity hypothesis," reduced contact of people with natural environmental features and biodiversity may adversely affect the human commensal microbiota and its immunomodulatory capacity. Analyzing atopic sensitization (i.e., allergic disposition) in a random sample of adolescents living in a heterogeneous region of 100 × 150 km, we show that environmental biodiversity in the surroundings of the study subjects' homes influenced the composition of the bacterial classes on their skin. Compared with healthy individuals, atopic individuals had lower environmental biodiversity in the surroundings of their homes and significantly lower generic diversity of gammaproteobacteria on their skin. The functional role of the Gram-negative gammaproteobacteria is supported by in vitro measurements of expression of IL-10, a key anti-inflammatory cytokine in immunologic tolerance, in peripheral blood mononuclear cells. In healthy, but not in atopic, individuals, IL-10 expression was positively correlated with the abundance of the gammaproteobacterial genus Acinetobacter on the skin. These results raise fundamental questions about the consequences of biodiversity loss for both allergic conditions and public health in general. [ABSTRACT FROM AUTHOR]

To cite this article: Zhang G, Candelaria P, Mäkelä JM, Khoo S-K, Hayden MC, von Hertzen L, Laatikainen T, Vartiainen E, Goldblatt J, Haahtela T, LeSouëf NP. Disparity of innate immunity-related gene effects on asthma and allergy on Karelia. Pediatr Allergy Immunol 2011; 22: 621-630. Abstract Background: We investigated the interactive effects of 11 innate immunity-related genes ( IL10, IL12b, IL8, TLR2, TLR4, CD14, IFNGR, CC16, IFNg, CMA1, and TGFB) and four IgE response genes ( IL4, IL13, IL4RA, and STAT6) with 'Western' or 'Eastern' environments/lifestyles on asthma and allergy in Karelian children. Methods: Karelian children (412 Finnish and 446 Russian) were recruited and assessed for a range of allergic conditions, with 24 single-nucleotide polymorphisms genotyped in 15 genes. Results: The genotype-phenotype relationships differed in Finnish and Russian Karelian children. The interaction between polymorphisms and the variable representing 'Western' and 'Eastern' environments/ lifestyles was significant for IL10-1082 (p = 0.0083) on current rhinitis, IL12b 6408 on current conjunctivitis (p = 0.016) and atopy (p = 0.034), IL8 781 on atopic eczema (p = 0.0096), CD14 -550 on current rhinitis (p = 0.022), IFNgR1 -56 on atopic eczema(p = 0.038), and STAT6 2964 on current itchy rash (p = 0.037) and total serum IgE (p = 0.042). In addition, the G allele of IL13 130 was associated with a lower level of total serum IgE in Finnish ( p = 0.003) and Russian (p = 0.01) children and overall (pooling the two populations together, p = 0.00006). After adjusting for multiple tests, the association between IL13 130 and IgE and the interactive effects of IL10-1082 on current rhinitis and IL8 781 on atopic eczema were significant by controlling a false-positive rate of 0.05 and 0.10, respectively. Conclusions: Living in an Eastern vs. Western environment was associated with a different genetic profile associated with asthma and allergy in the Karelian populations. [ABSTRACT FROM AUTHOR]

Dysregulated immune function is involved in the pathogenesis of many common human diseases. Living in urban, microbe-poor environment may have a profound influence on the immune function and eventually also on carcinogenesis. Unfortunately, few studies have thus far addressed the role of exposure to the environmental microbiota on the risk of cancer. Which mechanisms are broken in individuals prone to develop chronic inflammation in response to exposure that does not cause harm in others? Recent work in immunology has revealed that Th17 cells, a third subset of Th cells, and inflammatory cytokines, particularly IL-23, are closely linked with tumour-associated inflammation. Albeit the precise role of Th17 cells in cancer is still unclear and a matter of debate, accumulating evidence shows that Th17 cells are enriched in a wide range of human tumours, and that these tumour-derived Th17 cells may promote angiogenesis, tumour growth and inflammation. Regulatory T cells, in turn, appear to have counter-regulatory effects on Th17 cells and can inhibit their function. Thus, the regulatory network, induced and strengthened by continuous exposure to environmental microbiota, may play an important role in tumour immunobiology in preventing the establishment of chronic inflammation in its early phases. In addition, the discovery of the Toll-like receptor (TLR) system has brought micro-organisms to new light; continuous signalling via these TLRs and other receptors that sense microbial components is necessary for epithelial cell integrity, tissue repair, and recovery from injury. In this communication, we summarise the epidemiological data of living in environments with diverse microbial exposures and the risk of cancer, and discuss the related immunological mechanisms, focusing on the links between environmental microbiota, the Th17/IL-23 axis and cancer-associated inflammation. [ABSTRACT FROM AUTHOR]

Background: Modern lifestyle and urbanization have been associated with a raised risk for atopic diseases whereas early and long-term exposure to a farm environment confers protection against atopic sensitization. Immunomodulatory potential and microbiological characteristics of settled airborne dust from an urban house and a barn were examined. Methods: Pulmonary inflammation was induced in mice by repeated intranasal administration of dusts. Monocyte-derived human dendritic cells (moDCs) were exposed to dusts followed by coculture with purified naïve T cells. Cytokine/chemokine mRNA and protein levels were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay and flow cytometry. The dusts were analyzed by cloning and sequencing of 16S rRNA genes (290 sequences) for DNA, lipids, endotoxin and β-glucan, by live-dead staining, viable counting, isolation and identification of pure cultures (n = 76). Results: Repeated exposure to house dust elicited pulmonary eosinophilia in mice whereas exposure to barn dust elicited neutrophilic and lymphocytic airway inflammation. Stimulation of moDCs with urban house dust elicited expression of Th2-promoting OX40L and Jagged-1 costimulatory molecules. Dendritic cells (DCs) exposed to house dust directed naïve T cells towards Th2 responses. Exposure of DCs to barn dust elicited the development of Th1-dominated immune responses. Urban house dust contained bacterial debris almost exclusively of human commensal species (corynebacteria, streptococci) whereas barn dust comprised mainly intact, viable bacteria of high diversity and no commensal species. Conclusion: Contact to debris originating from human commensal bacteria in urban house dust elicited a Th2-type response whereas barn dust with high bacterial diversity directed the cells towards a Th1 response. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple living conditions and farming environment have been associated with reduced risk for allergic diseases such as atopy and asthma but the factors responsible for this effect remain unresolved. We examined the bacterial composition of house dusts obtained from Finnish and Russian Karelia, two adjacent areas with high and low occurrence of atopic diseases respectively. Two dust mixes, both composed of 10 randomly selected dust samples from 349 Finnish and 417 Russian Karelian households were studied for bacterial biomarkers (DNA, Limulus-active endotoxin, 3-OH fatty acids, muramic acid) and for 16S rRNA gene sequences. Overall, the DNA cloning revealed more taxons (94 different genera) of dustborne bacteria than seen in any previous study on residential environments. Majority (67%) of the bacterial DNA clones in house dust from the low-allergy Russian Kareliarepresented Gram-positive bacteria ( Firmicutes and Actinobacteria), predominantly Staphylococcaceae and Corynebacteriaceae. Russian Karelian dust showed up to 20-fold higher contents of muramic acid (marker of Gram-positive bacteria) and a sevenfold higher number of clones of animal-associated species, whereas in Finnish Karelian dust Gram-negatives (mainly Proteobacteria) predominated. Clones of plant-associated bacterial species and of chloroplast, indicating plant biomass, were more numerous in Finnish than in Russian Karelian dust. In conclusion, this study revealed major disparities between Finnish and Russian house dusts. The higher bacterial content and the predominance of Gram-positive bacteria in Russian dust may have implications for occurrence of atopy. [ABSTRACT FROM AUTHOR]

Background: Evidence of the influence of pathogen exposure on the development of atopy and atopic disease is not unequivocal. We investigated the association between markers of infections and occurrence of atopy among adults in eastern Finland and western Russia, two adjacent areas with profound differences in living conditions and lifestyles. Methods: Randomly selected adults aged 25–54 years from Finland (n = 790) and from Russia (n = 387) participated in the study. Skin prick tests were performed to 11 common airborne allergens, and at least one positive prick reaction was considered to indicate atopy. Antibodies to different pathogens including hepatitis A virus (HAV), Helicobacter pylori, Toxoplasma gondii, herpes simplex virus (HSV), Chlamydia pneumoniae and the periodontal pathogens Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were measured. Results: In Finland 34.3% and in Russia 23.3% of the study population was atopic (p < 0.001). Seroprevalences to all these pathogens were significantly higher among the Russians. In multivariate logistic regression analysis, only H. pylori was inversely associated with atopy in Russia. A further stepwise analysis revealed that H. pylori alone can explain 32% of the difference in atopy between the countries, and T. gondii, A. actinomycetemcomitans, HSV and C. pneumoniae had a slightly additive effect, whereas, unexpectedly, seropositivity to HAV and, to a lesser extent, P. gingivalis had an opposite effect. The net result of the stepwise analysis showed that 44% of the difference in atopy between the countries could be explained by seropositivity to these seven pathogens. Conclusions: Seropositivity to select pathogens, particularly to H. pylori, could explain a substantial part of the difference in atopy prevalence between Finland and Russia. Exposure to HAV was not associated with protection against atopy in this adult population. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A substantial increase in the prevalence of asthma in the Western world during the last few decades has led to a continuous search for novel factors that might be involved in the development of the disease. We carried out a study to clarify whether there is a relationship between severity of asthma and Chlamydia pneumoniae-specific titres at the group level and whether antibodies to the 60 kDa chlamydial heat shock protein (chsp60) are associated with asthma. A total of 116 (31 men, 85 women) consecutive asthma patients from a chest clinic were recruited and divided into 3 groups according to the severity of the disease: there were 13 asthmatics with severe, 54 with moderate and 49 with mild asthma. In addition, 50 (31 men, 19 women) consecutive blood donors were enrolled to serve as a control group. Sera for the measurements of specific IgG, IgA and IgM antibodies using a microimmunofluorescence test and of chsp60 using an enzyme immunoassay were obtained upon enrolment and also 3-4 months later from the asthma patients. Severe and moderate asthma were found to be strongly associated with elevated IgA antibody levels to C. pneumoniae [odds ratio (OR) 5.58, 95% confidence interval (CI) 1.31-23.72 for severe and OR 5.65, 95% CI 2.05-15.53 for moderate asthma] in a logistic regression model. Furthermore, in women, the occurrence of elevated IgA antibody levels and the age-adjusted geometric mean titres of IgA antibodies were significantly higher among the asthmatics than the controls (p=0.003 and 0.04, respectively). Antibodies to chsp60 occurred more frequently and in higher concentrations among the asthmatics than the controls, although the differences did not reach significance. In conclusion, severe and moderate asthma were significantly associated with elevated IgA antibody levels to C. pneumoniae suggestive of chronic infection. Antibodies to chsp60 did not prove to be a useful marker of such an infection among the asthmatics studied here. [ABSTRACT FROM AUTHOR]

The characteristic feature of Chlamydia is its tendency to cause chronic infections. It has been hypothesized that prior exposure to C. pneumoniae may lead to chronic infection and the development of associated chronic cardiopulmonary disease. Few studies have so far addressed the occurrence of chlamydial antibodies in an elderly, unselected population. This information is important for the development of possible treatment strategies. Chlamydial antibodies were analysed from 1179 serum samples obtained from 481 men and 698 women, aged 64 y and over, who participated in an epidemiological survey carried out in a Finnish rural district. Specific IgG and IgA antibodies were measured by the microimmunofluorescence (micro-IF) test. The criterion for seropositivity was defined as a titre of ≥32 for both IgG and IgA, independently of each other. C. pneumoniae IgG antibodies occurred in 91% of the men and 75% of the women. The respective figures for C. pneumoniae IgA antibodies were 57% and 28%. The geometric mean titres (GMT) rose with increasing age and were higher in men than in women. The prevalences of C. trachomatis IgG antibodies were 13% in men and 18% in women, and for IgA antibodies, 2% and 1%, respectively. C. psittaci antibodies were rare. Only 3% of the men and women were IgG seropositive, whereas the respective figures for IgA seropositivity were 0.4% and 0.1%. C. pneumoniae antibodies indicative of recurrent or chronic infection were common in the elderly. The geometric mean titres correlated positively with age and were higher in men than in women. Other chlamydial antibodies occurred in low titres. [ABSTRACT FROM AUTHOR]

von Hertzen L, Kaprio J, Koskenvuo M, Isoaho R, Saikku P (The Finnish Lung Health Association, Helsinki, Finland, Helsinki University, Department of Public Health, Helsinki University, Helsinki, Finland, University of Turku, Department of Public Health and General Practice, Turku, Finland and the National Public Health Institute, Oulu, Finland). Humoral immune response to Chlamydia pneumoniae in twins discordant for smoking. J Intern Med 1998; 244: 227–34. ObjectivesThe aim of this study was to investigate whether there is a relationship between smoking and Chlamydia pneumoniae specific antibody levels in generally healthy subjects, and whether this possible relationship is dose-dependent. DesignMatch pair study. Subjects. The study population comprised of 111 same-gender twin pairs from the Finnish Twin Cohort who in a previous study reported the highest discordance between smoking assessed as pack-years. Main outcome measuresSmoking and background data were obtained by a questionnaire, and C. pneumoniae specific serum IgG and IgA antibodies were measured by the micro-immunofluorescence (mIF) test. ResultsA significantly higher proportion of men with a history of smoking had elevated levels (a titre of ≥ 40) of serum IgA antibodies (P = 0.003), whereas in women, a significant difference between the pairs was found in the proprotion of IgG seropositive (a titre of ≥ 128) subjects (P = 0.03). Conditional logistic regression analysis revealed that the risk for elevated IgA antibodies suggestive of chronic infection was significantly increased in current or former smokers in men (odds ratio 5.0 with 95% confidence intervals of 1.45–17.3). No dose–response effect was found between smoking and IgG or IgA titres, neither even if men and women were analysed separately. ConclusionSmoking was significantly associated with elevated IgA antibody levels in men, supporting indirectly the hypothesis that smoking is a contributory factor in the establishment of chronic C. pneumoniae infection. [ABSTRACT FROM AUTHOR]

IgG subclass-specific antibodies to Chlamydia pneumoniae and chlamydial lipopolysaccharide (LPS) were analysed in paired sera obtained from 15 patients with primary C. pneumoniae pneumonia and from 16 pneumonia patients with reinfection, as well as in single sera of 40 subjects with possible chronic C. pneumoniae infection and 40 healthy controls. The microimmunofluorescence (MIF) method was used to measure total IgG, IgM and IgG subclass-specific antibodies to C. pneumoniae protein antigens and enzyme immunoassay (EIA) to measure antibodies against the LPS antigen. By MIF, IgG1 antibodies to C. pneumoniae were demonstrated in all individuals of the 3 patient groups and also in all healthy controls. IgG2 subclass antibodies were not found by MIF. IgG3 antibodies were detected in 40% of patients with primary infection, in 31% of patients with reinfection, in 25% of those with chronic infection and in 8% of the controls. IgG4 antibodies were associated with acute C. pneumoniae infection and were found in 13% of primary infections and 31% of reinfections. The subclass pattern of LPS antibodies resembled that of protein antibodies measured by MIF: IgG1 was the most common subclass among the antibodies to LPS. [ABSTRACT FROM AUTHOR]

Background: The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. Results: The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking "nature" to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. Conclusions: In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Low-grade inflammation, diet composition and health: current research evidence and its translation," by A. M. Minihane, S. Vinoy, and W. R. Russell and colleagues in the 2015 issue.

The composition of human microbiota is affected by a multitude of factors. Understanding the dynamics of our microbial communities is important for promoting human health because microbiota has a crucial role in the development of inflammatory diseases, such as allergies. We have studied the skin microbiota of both arms in 275 Finnish children of few months old to teenagers living in contrasting environments. We show that while age is a major factor affecting skin microbial composition, the living environment also discriminates the skin microbiota of rural and urban children. The effect of environment is age-specific; it is most prominent in toddlers but weaker for newborns and non-existent for teenagers. Within-individual variation is also related to age and environment. Surprisingly, variation between arms is smaller in rural subjects in all age groups, except in teenagers. We also collected serum samples from children for characterization of allergic sensitization and found a weak, but significant association between allergic sensitization and microbial composition. We suggest that physiological and behavioral changes, related to age and the amount of contact with environmental microbiota, jointly influence the dynamics of the skin microbiota, and explain why the association between the living environment skin microbiota is lost in teenager. [ABSTRACT FROM AUTHOR]

Presents a study on the prevalence of asthma in young Finnish men. How the increase in the prevalence of asthma has been nearly linear since the 1960s; Description of the study; Lack of reduction in asthma or allergic rhinitis.