Holistic view on health : two protective layers of biodiversity

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.Peer reviewe

Patterns in the skin microbiota differ in children and teenagers between rural and urban environments

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.Peer reviewe

A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism

Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70-0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FIN-RISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.Peer reviewe

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.Peer reviewe

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.peerReviewe

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 T(H)1 and a higher level of anti-inflammatory signaling, alleviating T(H)2-ype 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 T(H)2-driven inflammation, which relates to allergic diseases.Peer reviewe

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 factorsmight 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.Peer reviewe