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References
Roslund MI, Puhakka R, Grönroos M, et al. Biodiversity intervention improves immune regulation and health-associated commensal microbiota in daycare children.science adv. 2020;6(42):eaba2578.
Study objective
To experimentally determine whether naturally occurring soil bacteria in “green” vs. “normal” landscaped daycare centers influence the immune system inflammatory response in preschool children
Participant
75 preschool children (3-5 years) in Finland. All children received the same 2 meals and 1 snack per day as well as the same time outside per day (~1.5 hours) throughout the experiment. Researchers assessed activities outside of daycare (e.g., meals at home, outdoor/nature weekends, contact with animals) using surveys completed by parents and found minimal differences between groups.
Children were excluded from the study if they had any of the following characteristics: presence of an immunodeficiency, autoimmune, or immunoregulatory disease (e.g., human immunodeficiency virus). [HIV], Crohn's disease, Down syndrome); current use of immunosuppressive medications (e.g. corticosteroids); or current use of antibiotics or probiotics.
Draft
Researchers assessed children before (@Day 0) and after (@Day 28) landscaping or no-change control at the urban daycare centers they attended. They included 3 setting types:
- Standard-Kindertagesstätte (keine Änderung der negativen Kontrolleinstellung): Kies- und Betonhof mit eingebauten Elementen (z. B. Schaukel, Klettergerüst und Sandkasten)
- Naturkindergarten (keine Veränderung Positivkontrolle): Hof und Umgebung mit natürlich vorkommenden Waldelementen (z. B. Heidelbeersträucher, Heidekraut, Moose, Rispengras, Torf)
- Begrünung der Kindertagesstätte (variable Einstellung): Standard-Kindertagesstättenhof @Tag 0, mit Waldelementen, die gebracht und gepflanzt werden, um die Ähnlichkeit mit der Naturtagesstätte bis zum 28. Tag zu erleichtern.
The researchers took pre- and post-measurements of skin and stool bacteria as well as blood samples from all participants. They also measured soil/soil bacteria @Day 0 and @Day 28 in all 3 environments in a standardized manner (e.g., next to daycare front door, swing set, jungle gym, sandbox).
Target parameters
Researchers took blood samples before and after the intervention to assess the status of children's immune systems. Specifically, they measured the following inflammatory immune markers (cytokines):
- Interleukin 10 (IL-10): ein wichtiges entzündungshemmendes Interleukin-Zytokin
- Transforming Growth Factor-beta 1 (TGF-β1): ein wichtiges entzündungshemmendes regulatorisches Zytokin
- Interleukin 17A (IL-17A): ein wichtiges entzündungsförderndes regulatorisches Zytokin.
Blood samples were also used to measure regulatory T cells (Treg), modulating white blood cells that influence the inflammatory immune response. The researchers also measured skin and stool bacteria as well as environmental soil bacteria to assess any changes between groups before and after the study.
Key insights
Soil samples from all 3 daycare centers on day 0 showed extensive presence of multiple classes of bacteria, as expected. Pre-intervention microbial diversity was significantly higher in the nature day care group than in the standard day care group (which included the pre-intervention greening day care group). Severely elevated IL-10 levels were found in children attending Nature daycare (P=0.0000023). Conversely, children in the day 0 standard day care group had lower TGF-β1 levels (P=0.01).
The “greening” of a kindergarten led to changes in soil, skin and stool bacteria that directly corresponded to changes in immune function.
On day 28, a significant increase in bacterial abundance and diversity was measured for the Greening nursery, up to eight times what was measured in the standard nursery. This was reflected in increased microbial diversity on the skin and stool samples of children in the Greening Kita group, which were similar to the findings in the Nature Kita group.
Most importantly, changes in soil, skin and stool bacteria corresponded directly to changes in measures of immune function for the greening day care group. The increase in microbial diversity led to a significant increase in anti-inflammatory TGF-β1 (P=0.01) and Treg (P=0.016) and decreases in the pro-inflammatory IL-17A (P=0.002). In particular, a decrease in IL-17A was most strongly associated with an increase in stool bacteriaFaecalibacterium prausnitzii(P=0.045), which has been shown to have beneficial immunomodulatory properties for people with Crohn's disease.1
Practice implications
This is the first field study to experimentally measure how environmental bacteria modulate the human immune system. Environmental factors have been known to influence immune system function for decades, beginning with the development of the “hygiene hypothesis” in 1989.2Since then, several studies have demonstrated the importance of microbial biodiversity in influencing immune system function.3.4This also includes the refined "Old Friends Hypothesis", which suggests that atopic diseases (e.g. allergies, asthma, eczema) and autoimmune diseases (e.g. multiple sclerosis, rheumatoid arthritis, Crohn's disease) are increasing in developed countries compared to developing countries as a result of microbial Th1/Th2/Th17/Treg immune modulation, which is more representative of our traditional evolutionary past.5A past in which our prehistoric ancestors were physically exposed to the rich microbial biodiversity of the natural world around them.6.7
The evidence for the Old Friends hypothesis is not based solely on comparisons between developed and developing countries. Even in developed countries, there are many studies demonstrating the health benefits of people, especially children, being exposed to microbial environments with greater biodiversity. Writings about these benefits are common even in popular lay literature.8.9A common way to achieve these benefits is to spend time outdoors where naturally occurring microbial diversity is high. Several studies have shown the benefits of such outdoor activities on rates of atopic and autoimmune diseases.10,11as well as mental illnesses such as depression and anxiety12,13mediated by neuronal anti-inflammatory and neurotransmitter-supportive changes caused by microbial exposures.14-16This is, of course, in addition to all the other mental and physical benefits known to result from spending time outdoors, including increased physical activity, social interaction, creative play, empathy development, academic performance, etc.17-19
Prior to this current study, all research on the Hygiene/Old Friends hypotheses was either observational (making associations across large population-based data sets) or laboratory-basedin vivoVaccination trials to measure the effects of specific microbial species. This field study shows for the first time that altering real-world environments can alter environmental microbiomes in ways that have measurable, impactful effects on human inflammatory status and immune system function.
restrictions
This was a well-designed study that established a direct link between changes in external and internal environmental microbes and immune system function. A more definitive association could have been made by directly exposing participants to selected microbial species, but this association was made elsewhere.20This study did not show how long participants' microbial and immunological changes lasted after day 28. Future studies could include a crossover or washout period after exposure to determine longevity. Additionally, a longitudinal study with clinical populations (e.g., children with atopic or autoimmune diagnoses) would be useful to determine the therapeutic value of this type of exposure.
Conclusion
The world we live in has complex and intimate effects on our health and well-being. As the holistic worldview says, “everything is connected.” In modern times, many people have sought to distance themselves from the natural world around them, often to their detriment. Exploring ways to return to a more relational interaction with our environment makes biological sense and supports the physiological functioning of our body's adaptations over millions of years. Research like this daycare study shows that simple environmental adjustments can positively impact the health and lives of ourselves and our children.