Chronic kidney disease stage is associated with the number of risk factors in type 2 diabetes patients (STages Of NEphropathy in type 2 diabetes and Heart Failure - STONE HF).

AIMS: To study the association between risk factors and chronic kidney disease (CKD), and characterize medication use in Finnish primary care type 2 diabetes (T2D) patients. METHODS: Data on clinical characteristics, laboratory measurements, and medications were collected from medical records. The primary outcome measure was notable CKD (stage 3-5, eGFR <60 ml/min/1.73 m2) and/or increased albuminuria. The explanatory variables were individual risk factors and risk factor groups based on their number (0-2, 3-4, 5-6, >7). Spearman's rank correlation coefficient and risk ratio analysis were used to analyze the association between the number of risk factors and CKD stage, and between the number of risk factors and notable CKD, respectively. RESULTS: Altogether, 1335 patients with T2D in 60 Finnish primary care centers were recruited for this cross-sectional study. Three-quarters of T2D patients had 3 risk factors and 36% had ≥ 5 risk factors. Compared to patients with 0-2 risk factors, patients with 3-4, 5-6, and ≥ 7 risk factors had a 5.5-fold, 9.9-fold, and 15.9-fold risk of notable CKD (p < 0.001), respectively. Heart failure was most strongly associated with notable CKD (risk ratio, 3.7; p < 0.001). CONCLUSIONS: Number of risk factors was strongly associated with advanced-stage CKD.

Distinct healthy and atopic canine gut microbiota is influenced by diet and antibiotics.

The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle-diet, antibiotic use, and residential environment with housing and family-on the gut microbiota of healthy and owner-reported atopic pet dogs, searching for associations between the lifestyle factors, atopy and microbiota. The results showed that atopic and healthy dogs had contrasting gut microbial composition. The gut microbiota also differed between two breeds, Labrador Retriever and Finnish Lapphund, selected for our study. Among all lifestyle factors studied, diet was most significantly associated with gut microbiota but only weakly with atopic symptoms. Thus, diet- and atopy-associated changes in the microbiota were not interrelated. Instead, the severity of symptoms was positively associated with the usage of antibiotics, which in turn was associated with the microbiota composition. Urban lifestyle was significantly associated with the increased prevalence of allergies but not with the gut microbiota. Our results from pet dogs supported previous evidence from humans, demonstrating that antibiotics, gut microbiota and atopic manifestation are interrelated. This congruence suggests that canine atopy might be a promising model for understanding the aetiology of human allergy.

A short history from Karelia study to biodiversity and public health interventions.

Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002-2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008-2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022-2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.

Effects of phenotypic variation on consumer coexistence and prey community structure.

A popular idea in ecology is that trait variation among individuals from the same species may promote the coexistence of competing species. However, theoretical and empirical tests of this idea have yielded inconsistent findings. We manipulated intraspecific trait diversity in a ciliate competing with a nematode for bacterial prey in experimental microcosms. We found that intraspecific trait variation inverted the original competitive hierarchy to favour the consumer with variable traits, ultimately resulting in competitive exclusion. This competitive outcome was driven by foraging traits (size, speed and directionality) that increased the ciliate's fitness ratio and niche overlap with the nematode. The interplay between consumer trait variation and competition resulted in non-additive cascading effects-mediated through prey defence traits-on prey community assembly. Our results suggest that predicting consumer competitive population dynamics and the assembly of prey communities will require understanding the complexities of trait variation within consumer species.

Ten-year projection of white-nose syndrome disease dynamics at the southern leading-edge of infection in North America.

Predicting the emergence and spread of infectious diseases is critical for the effective conservation of biodiversity. White-nose syndrome (WNS), an emerging infectious disease of bats, has resulted in high mortality in eastern North America. Because the fungal causative agent Pseudogymnoascus destructans is constrained by temperature and humidity, spread dynamics may vary by geography. Environmental conditions in the southern part of the continent are different than the northeast, where disease dynamics are typically studied, making it difficult to predict how the disease will manifest. Herein, we modelled WNS pathogen spread in Texas based on cave densities and average dispersal distances of hosts, projecting these results out to 10 years. We parameterized a predictive model of WNS epidemiology and its effects on bat populations with observed cave environmental data. Our model suggests that bat populations in northern Texas will be more affected by WNS mortality than southern Texas. As such, we recommend prioritizing the preservation of large overwintering colonies of bats in north Texas through management actions. Our model illustrates that infectious disease spread and infectious disease severity can become uncoupled over a gradient of environmental variation and highlight the importance of understanding host, pathogen and environmental conditions across a breadth of environments.

Immunological resilience and biodiversity for prevention of allergic diseases and asthma.

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.

Elevated rates of horizontal gene transfer in the industrialized human microbiome.

Industrialization has impacted the human gut ecosystem, resulting in altered microbiome composition and diversity. Whether bacterial genomes may also adapt to the industrialization of their host populations remains largely unexplored. Here, we investigate the extent to which the rates and targets of horizontal gene transfer (HGT) vary across thousands of bacterial strains from 15 human populations spanning a range of industrialization. We show that HGTs have accumulated in the microbiome over recent host generations and that HGT occurs at high frequency within individuals. Comparison across human populations reveals that industrialized lifestyles are associated with higher HGT rates and that the functions of HGTs are related to the level of host industrialization. Our results suggest that gut bacteria continuously acquire new functionality based on host lifestyle and that high rates of HGT may be a recent development in human history linked to industrialization.

Bacterial Signatures of Paediatric Respiratory Disease: An Individual Participant Data Meta-Analysis.

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies. Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (<18 years) microbiota in acute and chronic respiratory conditions, with >10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses. Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively. Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.

Simultaneous allergic traits in dogs and their owners are associated with living environment, lifestyle and microbial exposures.

Both humans and pet dogs are more prone to develop allergies in urban than in rural environments, which has been associated with the differing microbial exposures between areas. However, potential similarities in the microbiota, that associate with environmental exposures, in allergic dogs and owners has not been investigated. We evaluated skin and gut microbiota, living environment, and lifestyle in 168 dog-owner pairs. Due to partly different manifestations of allergies between species, we focused on aeroallergen sensitized humans and dogs with owner-reported allergic symptoms. Our results agree with previous studies: dog-owner pairs suffered simultaneously from these allergic traits, higher risk associated with an urban environment, and the skin, but not gut, microbiota was partly shared by dog-owner pairs. We further discovered that urban environment homogenized both dog and human skin microbiota. Notably, certain bacterial taxa, which were associated with living environment and lifestyle, were also related with allergic traits, but these taxa differed between dogs and humans. Thus, we conclude that dogs and humans can be predisposed to allergy in response to same risk factors. However, as shared predisposing or protective bacterial taxa were not discovered, other factors than environmental microbial exposures can mediate the effect or furry dog and furless human skin select different taxa.

Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence.

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.

Within-season changes in habitat use of forest-dwelling boreal bats.

Bats utilize forests as roosting sites and feeding areas. However, it has not been documented how bats utilize these habitats in the boreal zone with methods afforded by recent technological advances. Forest structure and management practices can create a variety of three-dimensional habitats for organisms capable of flight, such as bats. Here, we study the presence of boreal bats in a forest forming a mosaic of different age classes, dominant tree species, canopy cover, soil fertility, and other environmental variables, throughout their active season in the summer using passive ultrasound detectors. Our results indicate a preference for mature forest by Eptesicus nilssonii and a pooled set of Myotis bats. Both groups of bats also showed temporal changes in their habitat use regarding forest age. In June and July, both groups occurred more often in mature than young forests, but from August onwards, the difference in occurrence became less evident in Myotis and disappeared completely in E. nilssonii. In addition, E. nilssonii was more often present in forests with low canopy cover, and its occurrence shifted from coniferous forests to deciduous forests during the season. The results reflect the within-season dynamics of bat communities and their ability to utilize different types of forest as environmental conditions change. Yet, the results most importantly emphasize the importance of mature forests to bat diversity and the need to conserve such environments in the boreal zone.

Contrasting microbiotas between Finnish and Estonian infants: Exposure to Acinetobacter may contribute to the allergy gap.

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.

School environment associates with lung function and autonomic nervous system activity in children: a cross-sectional study.

Children are in contact with local environments, which may affect respiratory symptoms and allergic sensitization. We aimed to assess the effect of the environment and the walkability surrounding schools on lung function, airway inflammation and autonomic nervous system activity. Data on 701 children from 20 primary schools were analysed. Lung function, airway inflammation and pH from exhaled breath condensate were measured. Pupillometry was performed to evaluate autonomic activity. Land use composition and walkability index were quantified within a 500 m buffer zone around schools. The proportion of effects explained by the school environment was measured by mixed-effect models. We found that green school areas tended to be associated with higher lung volumes (FVC, FEV1 and FEF25-75%) compared with built areas. FVC was significantly lower in-built than in green areas. After adjustment, the school environment explained 23%, 34% and 99.9% of the school effect on FVC, FEV1, and FEF25-75%, respectively. The walkability of school neighbourhoods was negatively associated with both pupil constriction amplitude and redilatation time, explaining -16% to 18% of parasympathetic and 8% to 29% of sympathetic activity. Our findings suggest that the environment surrounding schools has an effect on the lung function of its students. This effect may be partially mediated by the autonomic nervous system.

Scaling up the effects of inbreeding depression from individuals to metapopulations.

Inbreeding is common in nature, and many laboratory studies have documented that inbreeding depression can reduce the fitness of individuals. Demonstrating the consequences of inbreeding depression on the growth and persistence of populations is more challenging because populations are often regulated by density- or frequency-dependent selection and influenced by demographic and environmental stochasticity. A few empirical studies have shown that inbreeding depression can increase extinction risk of local populations. The importance of inbreeding depression at the metapopulation level has been conjectured based on population-level studies but has not been evaluated. We quantified the impact of inbreeding depression affecting the fitness of individuals on metapopulation persistence in heterogeneous habitat networks of different sizes and habitat configuration in a context of natural butterfly metapopulations. We developed a spatial individual-based simulation model of metapopulations with explicit genetics. We used Approximate Bayesian Computation to fit the model to extensive demographic, genetic and life-history data available for the well-studied Glanville fritillary butterfly (Melitaea cinxia) metapopulations in the Åland islands in SW Finland. We compared 18 semi-independent habitat networks differing in size and fragmentation. The results show that inbreeding is more frequent in small habitat networks, and consequently, inbreeding depression elevates extinction risks in small metapopulations. Metapopulation persistence and neutral genetic diversity maintained in the metapopulations increase with the total habitat amount in and mean patch size of habitat networks. Dispersal and mating behaviour interact with landscape structure to determine how likely it is to encounter kin while looking for mates. Inbreeding depression can decrease the viability of small metapopulations even when they are strongly influenced by stochastic extinction-colonization dynamics and density-dependent selection. The findings from this study support that genetic factors, in addition to demographic factors, can contribute to extinctions of small local populations and also of metapopulations.

Soil exposure modifies the gut microbiota and supports immune tolerance in a mouse model.

BACKGROUND: Sufficient exposure to natural environments, in particular soil and its microbes, has been suggested to be protective against allergies. OBJECTIVE: We aim at gaining more direct evidence of the environment-microbiota-health axis by studying the colonization of gut microbiota in mice after exposure to soil and by examining immune status in both a steady-state situation and during allergic inflammation. METHODS: The gastrointestinal microbiota of mice housed on clean bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing, and the data were combined with immune parameters measured in the gut mucosa, lung tissue, and serum samples. RESULTS: We observed marked differences in the small intestinal and fecal microbiota composition between mice housed on clean bedding or in contact with soil, with a higher proportion of Bacteroidetes relative to Firmicutes in the soil group. The housing environment also influenced mouse intestinal gene expression, as shown by upregulated expression of the immunoregulatory markers IL-10, forkhead box P3, and cytotoxic T lymphocyte-associated protein 4 in the soil group. Importantly, using the murine asthma model, we found that exposure to soil polarizes the immune system toward TH1 and a higher level of anti-inflammatory signaling, alleviating TH2-type allergic responses. The inflammatory status of the mice had a marked influence on the composition of the gut microbiota, suggesting bidirectional communication along the gut-lung axis. CONCLUSION: Our results provide evidence of the role of environmentally acquired microbes in alleviating against TH2-driven inflammation, which relates to allergic diseases.

Ecology determines how low antibiotic concentration impacts community composition and horizontal transfer of resistance genes.

Low concentrations of antibiotics have numerous effects on bacteria. However, it is unknown whether ecological factors such as trophic interactions and spatial structuring influence the effects of low concentrations of antibiotics on multispecies microbial communities. Here, we address this question by investigating the effects of low antibiotic concentration on community composition and horizontal transfer of an antibiotic resistance plasmid in a 62-strain bacterial community in response to manipulation of the spatial environment and presence of predation. The strong effects of antibiotic treatment on community composition depend on the presence of predation and spatial structuring that have strong community effects on their own. Overall, we find plasmid transfer to diverse recipient taxa. Plasmid transfer is likely to occur to abundant strains, occurs to a higher number of strains in the presence of antibiotic, and also occurs to low-abundance strains in the presence of spatial structures. These results fill knowledge gaps concerning the effects of low antibiotic concentrations in complex ecological settings.

Skin microbiota and allergic symptoms associate with exposure to environmental microbes.

A rural environment and farming lifestyle are known to provide protection against allergic diseases. This protective effect is expected to be mediated via exposure to environmental microbes that are needed to support a normal immune tolerance. However, the triangle of interactions between environmental microbes, host microbiota, and immune system remains poorly understood. Here, we have studied these interactions using a canine model (two breeds, n = 169), providing an intermediate approach between complex human studies and artificial mouse model studies. We show that the skin microbiota reflects both the living environment and the lifestyle of a dog. Remarkably, the prevalence of spontaneous allergies is also associated with residential environment and lifestyle, such that allergies are most common among urban dogs living in single-person families without other animal contacts, and least common among rural dogs having opposite lifestyle features. Thus, we show that living environment and lifestyle concurrently associate with skin microbiota and allergies, suggesting that these factors might be causally related. Moreover, microbes commonly found on human skin tend to dominate the urban canine skin microbiota, while environmental microbes are rich in the rural canine skin microbiota. This in turn suggests that skin microbiota is a feasible indicator of exposure to environmental microbes. As short-term exposure to environmental microbes via exercise is not associated with allergies, we conclude that prominent and sustained exposure to environmental microbiotas should be promoted by urban planning and lifestyle changes to support health of urban populations.